IdA string | IdB string | labels int64 | mechanism string | effect string | score float64 | sentence string | signor_id string |
|---|---|---|---|---|---|---|---|
Q05397 | Q6ZMU5 | 0 | ubiquitination | down-regulates quantity by destabilization | 0.326 | Because RING disrupted MG53 mutants (C14A and DeltaR) did not induce FAK ubiquitination and degradation, the RING domain was determined to be required for MG53 induced FAK ubiquitination. | SIGNOR-278648 |
P61586 | Q8WZ64 | 0 | gtpase-activating protein | down-regulates activity | 0.514 | 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-260453 |
O14965 | P41208 | 1 | phosphorylation | up-regulates | 0.516 | Our studies show that aurora a phosphorylates centrin at serine 170 in vitro and that the serine 170 phosphorylation affects the stability of centrin by regulating its interaction with apc/c. finally we demonstrated that phosphorylation of centrin serine 170 is an absolute requirement for aurora a-mediated centriole amplification. | SIGNOR-174686 |
P27986 | P06213 | 0 | phosphorylation | up-regulates activity | 0.67 | The alpha-type 85-kDa subunit of phosphatidylinositol 3-kinase is phosphorylated at tyrosines 368, 580, and 607 by the insulin receptor. | SIGNOR-251321 |
Q00535 | Q13794 | 1 | phosphorylation | down-regulates | 0.356 | We show that noxa is phosphorylated on a serine residue (s(13)) in the presence of glucose. Phosphorylation promotes its cytosolic sequestration and suppresses its apoptotic function. We identify cdk5 as the noxa kinase | SIGNOR-170357 |
P45973 | Q15329 | 0 | transcriptional regulation | down-regulates quantity by repression | 0.2 | We identified for E2F5 a repressor function for HP1a expression. | SIGNOR-261591 |
P62877 | Q00653 | 1 | ubiquitination | up-regulates | 0.281 | Mechanism of processing of the nf-kappa b2 p100 precursor: identification of the specific polyubiquitin chain-anchoring lysine residue and analysis of the role of nedd8-modification on the scf(beta-trcp) ubiquitin ligase. | SIGNOR-120342 |
P14921 | P24821 | 1 | transcriptional regulation | up-regulates quantity by expression | 0.2 | Sp1 and Ets1 are potent transactivators of the TN-C promoter. | SIGNOR-261599 |
Q9P1W9 | O00409 | 0 | transcriptional regulation | down-regulates quantity by repression | 0.297 | CHES1/FOXN3 regulates cell proliferation by repressing PIM2 and protein biosynthesis. | SIGNOR-261607 |
Q5S007 | P46459 | 1 | phosphorylation | up-regulates activity | 0.367 | LRRK2 phosphorylates full-length NSF at threonine 645 in the ATP binding pocket of D2 domain. Functionally, NSF phosphorylated by LRRK2 displays enhanced ATPase activity and increased rate of SNARE complex disassembling. | SIGNOR-277196 |
Q05397 | P46108 | 0 | phosphorylation | up-regulates activity | 0.733 | Tyrosine phosphorylation FAK was strictly dependent upon c-Crk II expression | Crk-inducible FAK tyrosine phosphorylation was completely abrogated by co-expression with R38K Crk (lane 2), and decreased by co-expression with W170K Crk (lane 3), indicating that the SH2 domain of c-Crk is absolutely essential for this effect. In contrast, mutants in the C-terminus of Crk that include Y222F c-Crk, which abrogates the c-Abl phosphorylation site, and W276K Crk, which mutates the C-terminal SH3 domain, modestly increased FAK activation compared to wild-type c-Crk II. | SIGNOR-250777 |
P35568 | P27361 | 0 | phosphorylation | down-regulates activity | 0.707 | 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-123177 |
Q92993 | Q02156 | 0 | phosphorylation | up-regulates activity | 0.365 | At least two TIP60 residues, Thr298 and Ser300, can be targeted in vitro by PKCepsilon.|In vitro, protein kinase C epsilon phosphorylates Tat-interactive protein 60 kDa on at least two sites within the acetyltransferase domain. | SIGNOR-279309 |
P15941 | P06239 | 0 | phosphorylation | up-regulates activity | 0.46 | The present results demonstrate that Lck phosphorylation of MUC1 on Y-46 also increases binding of MUC1 and beta-catenin. The results further show that ZAP-70 phosphorylation of MUC1-CD stimulates the interaction of MUC1 and beta-catenin | SIGNOR-249358 |
P62136 | P31749 | 1 | dephosphorylation | down-regulates activity | 0.426 | Here, we identify PP1 as a serine/threonine phosphatase that associates with and dephosphorylates AKT in breast cancer cells|The heat shock protein 90 inhibitor geldanamycin and the ErbB inhibitor ZD1839 promote rapid PP1 phosphatase-dependent inactivation of AKT in ErbB2 overexpressing breast cancer cells | SIGNOR-252603 |
P10636-4 | Q96L34 | 0 | phosphorylation | down-regulates activity | 0.419 | AMPK phosphorylation inhibits tau binding of microtubules. In order to study further the phosphorylation of tau by AMPK, we compared phosphorylation of tau by MARK4 or AMPK using a panel of phospho-tau antibodies (Figure 2A). Five phosphorylation sites common to both kinases were identified (Thr231, Ser262, Ser356, Ser396 and Ser422). In addition, AMPK, but not MARK4, was capable of phosphorylating Ser214 (Figure 2A). | SIGNOR-273934 |
P43403 | P29353 | 1 | phosphorylation | up-regulates | 0.677 | The syk-family kinases (syk and zap-70) were able to phosphorylate the y239 and y240 sites, and less efficiently the y317 site on shc1 (iso2). | SIGNOR-59659 |
P67775 | Q92769 | 1 | dephosphorylation | down-regulates activity | 0.281 | In contrast, in the present work, PPP2CA reduced HDAC2 S394 phosphorylation.|We postulated that PPP2CA would negatively regulate phospho dependent HDAC2 activity. | SIGNOR-277049 |
Q00535 | P29474 | 1 | phosphorylation | down-regulates | 0.371 | Together, our data suggest that cdk5 can phosphorylate enos at the ser-113 site and down-regulate enos-derived no levels. | SIGNOR-164080 |
P68400 | Q92598 | 1 | phosphorylation | down-regulates activity | 0.329 | Protein kinase CK2 phosphorylates Hsp105 alpha at Ser509 and modulates its function. | the phosphorylation of Hsp105 alpha at Ser(509) abolished the inhibitory activity of Hsp105 alpha in vitro. | SIGNOR-250901 |
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 |
Q9H992 | P10636 | 1 | ubiquitination | down-regulates activity | 0.2 | We have identified and characterized axotrophin, a protein that binds and preferentially mono-ubiquitinates tau protein. | SIGNOR-278655 |
P54252 | Q9UNE7 | 0 | ubiquitination | down-regulates quantity by destabilization | 0.51 | Although our data show that CHIP may associate with Atx3 to ubiquitinate Atx3 in vitro, we still wonder whether CHIP is directly involved in the degradation of Atx3.|As a result, silencing of CHIP significantly increases the amount of Atx3 (XREF_FIG), suggesting that CHIP may down-regulate the Atx3 level. | SIGNOR-278667 |
Q16611 | O43464 | 1 | relocalization | up-regulates | 0.295 | Bax and/or bak-mediated release of pro-apoptotic mediators including smac/diablo and omi | SIGNOR-118908 |
Q86U44 | P00533 | 1 | transcriptional regulation | up-regulates quantity by expression | 0.331 | Here we find that METTL3 promotes translation of certain mRNAs including epidermal growth factor receptor (EGFR) and the Hippo pathway effector TAZ in human cancer cells. | SIGNOR-265954 |
P11387 | P68400 | 0 | phosphorylation | up-regulates activity | 0.383 | In vitro kinase assays demonstrated that Ser(10) can be phosphorylated by casein kinase II, Ser(21) can be phosphorylated by protein kinase Calpha, and Ser(112) and Ser(394) can be phosphorylated by Cdk1.Collectively these results indicate that topo I is phosphorylated during mitosis at multiple sites, one of which enhances DNA relaxation activity in vitro and interaction with DNA in cells. | SIGNOR-276155 |
P11309 | Q9UM11 | 1 | phosphorylation | down-regulates activity | 0.317 | Pim-1 phosphorylates Cdh1 and impairs binding of this protein to another APC/C complex member, CDC27. These modifications inhibit Skp2 from degradation.Pim-1 Impairs Cdh1 and CDC27 Interaction and Phosphorylates Cdh1. | SIGNOR-259820 |
Q9UQM7 | P00533 | 1 | phosphorylation | down-regulates activity | 0.371 | We show that serines 1046/1047 are sites for CaM kinase II phosphorylation, although there is a preference for serine 1047, which resides within the consensus -R-X-X-S-. In addition, we have identified major phosphorylation sites at serine 1142 and serine 1057, which lie within a novel -S-X-D- consensus. Mutation of serines 1046/1047 in full-length EGFR enhanced both fibroblast transformation and tyrosine autokinase activity that was significantly potentiated by additional mutation of serines 1057 and 1142. A single CaM kinase II site was also identified at serine 744 within sub-kinase domain III, and autokinase activity was significantly affected by mutation of this serine to an aspartic acid making this site appear constitutively phosphorylated. We have addressed the mechanism by which CaM kinase II phosphorylation of the EGFR might regulate receptor autokinase activity and show that this modification can hinder association of the cytoplasmic tail with the kinase domain to prevent an enzyme-substrate interaction. | SIGNOR-250621 |
Q06413 | P35580 | 1 | transcriptional regulation | up-regulates quantity by expression | 0.345 | Myocyte enhancer factor-2 and serum response factor binding elements regulate fast Myosin heavy chain transcription in vivo. We show that the upstream promoter region of the gene most abundantly expressed in mouse skeletal muscles, IIb MyHC, retains binding activity and transcriptional activation for three positive transcription factors, the serum response factor, Oct-1, and myocyte enhancer factor-2, whereas the other two genes (IIa and IId/x) have nucleotide substitutions in these sites that reduce binding and transcriptional activation | SIGNOR-238769 |
P17612 | Q01094 | 1 | phosphorylation | up-regulates activity | 0.2 | We confirmed the phosphorylation of T130, S235, and S364 by developing monoclonal antibodies against phospho-specific forms of these sites and showed that their phosphorylation is cell cycle-dependent. According to our results, PKA-mediated phosphorylation of E2F1 by PKA inhibits proliferation and glucose uptake and induces caspase-3 activation and senescence. | SIGNOR-277537 |
Q8WV24 | O14965 | 0 | phosphorylation | down-regulates quantity by destabilization | 0.447 | Aurora A directly phosphorylates PHLDA1 leading to its degradation. Aurora A phosphorylates PHLDA1 at Ser 98. | SIGNOR-273545 |
P48730 | Q96T88 | 1 | phosphorylation | up-regulates | 0.245 | We further show that uhrf1 physically interacts with _-trcp1 in a manner dependent on phosphorylation of serine 108 (s108(uhrf1)) within the dsg degron. Furthermore, we demonstrate that s108(uhrf1) phosphorylation is catalyzed by casein kinase 1 delta (ck1_) and is important for the recognition of uhrf1 by scf(_-trcp). | SIGNOR-200349 |
P42224 | P29597 | 0 | phosphorylation | up-regulates activity | 0.775 | Co-expression of Stat1 with Tyk2, Jak1, or Jak2 resulted in the specific tyrosine phosphorylation of Stat1 at Tyr701Phosphorylation of purified Stat1 was necessary and sufficient for the acquisition of DNA binding activity. | SIGNOR-246943 |
Q9UQ88 | O95238 | 1 | phosphorylation | down-regulates quantity by destabilization | 0.356 | In this study we provide evidence that the cell cycle kinase CDK11p58, a protein involved in G2/M transition and degradation of several transcription factors, directly interacts with and phosphorylates SPDEF on serine residues|Western blot analysis demonstrated that only one of the mutant constructs, consisting of mutations of serine 238, 242 and 243, resulted in increased levels of SPDEF protein expression as compared to wild type SPDEF, leading to subsequent ubiquitination and degradation of SPDEF through the proteasome pathway.| | SIGNOR-273022 |
Q08050 | P11802 | 0 | phosphorylation | up-regulates | 0.624 | We identified the forkhead box m1 (foxm1) transcription factor as a common critical phosphorylation target. Cdk4/6 stabilize and activate foxm1, thereby maintain expression of g1/s phase genes, suppress the levels of reactive oxygen species (ros), and protect cancer cells from senescence. | SIGNOR-177266 |
P49639 | O15550 | 0 | transcriptional regulation | up-regulates quantity by expression | 0.403 | Evidence for direct involvement of UTX in regulation of HOX gene activity was demonstrated through UTX knockdown experiments in HEK293T cells in which loss of UTX induced transcriptional repression of HOXA and HOXC clusters. | SIGNOR-260019 |
P30304 | Q13535 | 0 | phosphorylation | down-regulates activity | 0.643 | ATR and CHK1 mediated loss of CDC25A activity suspends CDKs, such as CDK2, in an inactive phosphorylated state, blocking initiation of DNA replication origins.|In the presence of replication stalling, activated CHK1 and ATR phosphorylates CDC25A and promotes its degradation. | SIGNOR-280183 |
P19484 | Q14457 | 1 | transcriptional regulation | up-regulates quantity by expression | 0.409 | As expected, we found that glucose deprivation induced the binding of TFEB (Figure S4C) and ACSS2 (Figure S4D) to the promoter regions of MAP1LC3B, ATG3, and WIPI-1 as well as mRNA (Figure 3H) and protein (Figure 3I) expression of these genes; | SIGNOR-276558 |
P01106 | Q13616 | 1 | transcriptional regulation | up-regulates quantity by expression | 0.483 | Furthermore, c-myc activation can also promote the degradation of p27kip1 protein by directly activating the cul1 gene, which encodes a critical component of the ubiquitin ligase scfskp2 | SIGNOR-102749 |
Q15759 | Q12888 | 1 | phosphorylation | down-regulates activity | 0.2 | Here we show that 53BP1 is phosphorylated during mitosis on two residues, T1609 and S1618, located in its well-conserved ubiquitination-dependent recruitment (UDR) motif.|Dephosphorylation enables the recruitment of 53BP1 to double-strand DNA breaks |phosphorylation of T1609 is likely to be mediated by p38 MAPK | SIGNOR-264447 |
Q05086 | P49815 | 1 | ubiquitination | down-regulates quantity by destabilization | 0.629 | An in vivo ubiquitination assay was done to reveal that E6AP promoted the ubiquitination of TSC2 independent of HPV16 E6. We further found that TSC2 bound E6AP in the presence as well as in the absence of HPV16 E6. The binding regions on E6AP and TSC2 have been identified as amino acid (aa) 260-316, aa 428-500 and aa 1-175, aa 1251-1807, respectively. Taken together, degradation of TSC2 is mediated by E6AP ubiquitin ligase. | SIGNOR-271396 |
P35813 | O14920 | 1 | dephosphorylation | down-regulates | 0.308 | Using a functional genomic approach, we have identified two protein serine/threonine phosphatases, ppm1a and ppm1b, as ikkbeta phosphatases. Overexpression of ppm1a or ppm1b results in dephosphorylation of ikkbeta at ser177 and ser181 and termination of ikkbeta-induced nf-kappab activation | SIGNOR-181659 |
P06239 | Q9Y2R2 | 0 | dephosphorylation | down-regulates activity | 0.751 | In vitro experiments with purified recombinant proteins demonstrated that PTPN22-D195A/C227S interacted directly with activated Lck, Zap70, and TCRzeta, confirming the initial substrate trap results. Native PTPN22 dephosphorylated Lck and Zap70 at their activating tyrosine residues Tyr-394 and Tyr-493, respectively, but not at the regulatory tyrosines Tyr-505 (Lck) or Tyr-319 (Zap70). Native PTPN22 also dephosphorylated TCRzeta in vitro and in cells, and its substrate trap variant co-immunoprecipitated with TCRzeta when both were coexpressed in 293T cells, establishing TCRzeta as a direct substrate of PTPN22. | SIGNOR-248836 |
P49841 | Q92908 | 1 | phosphorylation | down-regulates quantity by destabilization | 0.308 | We identified the AKT-repressed signal as glycogen synthase kinase 3 (GSK3)-catalyzed phosphorylation of Ser(37) on the long form of the transcription factor GATA6. Phosphorylation of GATA6 on Ser(37) promoted its degradation, thereby preventing GATA6 from repressing transcripts that are induced by TNF and attenuated by insulin. | SIGNOR-277241 |
P12931 | Q9NZQ3 | 1 | phosphorylation | up-regulates activity | 0.414 | These results indicate that phosphorylation of SPIN90 by Src is essential for its synaptic targeting. | SIGNOR-279387 |
Q13257 | P33981 | 0 | phosphorylation | up-regulates activity | 0.713 | Mps1 is an upstream component of the spindle assembly checkpoint, which, in human cells, is required for checkpoint activation in response to spindle damage but not apparently during an unperturbed mitosis. Mps1 also recruits Mad1 and Mad2 to kinetochores.|Thus, in human cells, Mps1 catalytic activity is required for spindle checkpoint function and recruitment of Mad2. | SIGNOR-252036 |
P27361 | O14994 | 1 | phosphorylation | up-regulates | 0.2 | A rare, missense polymorphism, s470n, was identified in the synapsin iii gene and appeared more frequently in individuals with schizophrenia than in controls. Ser470, was determined to be a substrate for mitogen-activated protein kinase, a downstream effector of neurotrophin action. | SIGNOR-121402 |
Q09472 | P35558 | 1 | acetylation | down-regulates quantity by destabilization | 0.546 | Acetylation Regulates Gluconeogenesis by Promoting PEPCK1 Degradation via Recruiting the UBR5 Ubiquitin Ligase|P300 Acetylates and Destabilizes PEPCK1|Furthermore, coexpression of P300 increased acetylation levels of wild-type PEPCK1, but not PEPCK13K/R, indicating that P300 acts on these lysine residues of PEPCK1 | SIGNOR-267603 |
P49840 | P24723 | 0 | phosphorylation | down-regulates | 0.321 | Furthermore, several pkc isotypes phosphorylate gsk-3 in vitro and in vivo. in the presence of atp, several isoforms (?, ___, _, ?, And of pkc phosphorylated both gsk-3? At ser 21 and gsk-3_ at ser 9 | SIGNOR-115730 |
Q01831 | P68400 | 0 | phosphorylation | up-regulates activity | 0.2 | CK2 kinase mediates XPC phosphorylation at serine 94, and also promotes recruitment of ubiquitinated XPC to the chromatin after UVB irradiation. | SIGNOR-277389 |
P19484 | P08236 | 1 | transcriptional regulation | up-regulates quantity by expression | 0.249 | Nucleus-Translocated ACSS2 Promotes Gene Transcription for Lysosomal Biogenesis and Autophagy|A chromatin immunoprecipitation (ChIP) assay with antibodies against TFEB or ACSS2 demonstrated that glucose deprivation results in the binding of TFEB (Figure 3D) and ACSS2 (Figure 3E) to the promoter regions of CTSA, GBA, GUSB, and LAMP1|These results indicated that TFEB and ACSS2 are mutually required for their binding to the promoter regions of lysosomal genes. In line with these findings, glucose deprivation induced mRNA (Figure 3F) and protein (Figure 3G) expression for these lysosomal genes, which was largely abrogated by knockin of ACSS2 mutants | SIGNOR-276553 |
Q969H0 | Q6U7Q0 | 1 | ubiquitination | down-regulates quantity by destabilization | 0.2 | CK1delta and GSK3beta kinases sequentially phosphorylate ZNF322A at serine-396 and then serine-391. Moreover, the doubly phosphorylated ZNF322A protein creates a destruction motif for the ubiquitin ligase FBXW7alpha leading to ZNF322A protein destruction. | SIGNOR-264898 |
P50548 | P06493 | 0 | phosphorylation | down-regulates | 0.2 | Consistent with the in vivo phosphorylation and inactivation by ras, erf is efficiently phosphorylated in vitro by erk2 and cdc2/cyclin b kinases, at sites similar to those detected in vivo. Furthermore, a single mutation at position 526 results in the loss of a specific phosphopeptide both in in vivo and in vitro (by erk2) labeling. Substitution of thr526 for glutamic acid also decreases the repression ability of erf | SIGNOR-29501 |
Q13177 | Q15746 | 1 | phosphorylation | down-regulates activity | 0.533 | PAK2 can directly phosphorylate MLCK, inhibiting its activity and limiting the development of isometric tension. PAK2 catalyzes MLCK phosphorylation on serine residues 439 and 991. | SIGNOR-250223 |
P11309 | Q01196 | 1 | phosphorylation | up-regulates activity | 0.269 | Furthermore, catalytically active Pim-1 kinase was able to phosphorylate Runx1 and Runx3 proteins and enhance the transactivation activity of Runx1 in a dose-dependent fashion.|Pim-1 potentiates transcriptional activity of the RUNX1 transcription factor. | SIGNOR-278976 |
P10636 | P49840 | 0 | phosphorylation | down-regulates | 0.429 | Tau is phosphorylated by gsk-3 at several sites found in alzheimer disease and its biological activity markedly inhibited only after it is prephosphorylated by a-kinase. | SIGNOR-60651 |
Q9UN36 | P53355 | 0 | phosphorylation | up-regulates activity | 0.273 | DAPK1 phosphorylates and activates N-myc downstream-regulated gene 2 (NDRG2), resulting in increased tau phosphorylation via a reduction in Pin1 expression ( xref ; xref ). | SIGNOR-279983 |
Q06830 | P00519 | 0 | phosphorylation | down-regulates activity | 0.387 | Inactivation of peroxiredoxin I by phosphorylation allows localized H(2)O(2) accumulation for cell signaling. To determine whether Prxs are phosphorylated, we subjected recombinant human PrxI and II to an in vitro kinase assay with two nonreceptor PTKs, Lck and Abl, in the presence of [γ-32P]ATP. Both PTKs phosphorylated PrxI and PrxII. Phosphorylation of the wild-type protein was detected, whereas that of the Y194F mutant was not (Figure 1B), indicating that Tyr194 is the only site of tyrosine phosphorylation. | SIGNOR-276278 |
P08253 | P01137 | 1 | cleavage | up-regulates | 0.555 | We also demonstrate that mmp-9, as well as its relative, mmp-2, cleave latent transforming growth factor-beta (tgf-beta), which constitutes a novel mechanism of tgf-beta activation | SIGNOR-74384 |
Q13555 | Q4G163 | 1 | phosphorylation | down-regulates activity | 0.2 | Activated CaMKII and polo-like kinase simultaneously phosphorylate and inactivate Emi2 [ xref , xref , xref , xref , xref ]). | SIGNOR-280200 |
P24666 | P06239 | 0 | phosphorylation | up-regulates activity | 0.354 | In co-transfected COS cells, Lck and Fyn caused phosphorylation of LMPTP. Most of the phosphate was located at Tyr-131, and some was also located at Tyr-132. Site-directed mutagenesis showed that Tyr-131 is important for the catalytic activity of LMPTP, and that thiophosphorylation of Tyr-131, and to a lesser degree Tyr-132, is responsible for the activation. | SIGNOR-251367 |
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 |
P49840 | Q6R327 | 1 | phosphorylation | down-regulates quantity by destabilization | 0.387 | We show that this process is dependent on glycogen synthase kinase 3 (GSK3): GSK3 was associated with rictor and directly phosphorylated the Thr-1695 site in a putative CDC4 phospho-degron motif of rictor; mutation of this site impaired the interaction between rictor and FBXW7, decreased rictor ubiquitination, and increased rictor stability. | SIGNOR-276899 |
Q96PU5 | P84022 | 1 | ubiquitination | down-regulates activity | 0.805 | Through its ww domain, nedd4l specifically recognizes a tgf-beta-induced phosphothr-protyr motif in the linker region, resulting in smad2/3 polyubiquitination and degradation | SIGNOR-232104 |
P12259 | P08246 | 0 | cleavage | up-regulates activity | 0.366 | Human neutrophil elastase activates human factor V but inactivates thrombin-activated human factor V|NH2-terminal sequence analysis of F.V treated with HNE indicated cleavage at Ile819 and Ile1484 under conditions during which the procofactor expressed enhanced cofactor activity in the prothrombinase complex. | SIGNOR-263637 |
Q9BZL6 | P17252 | 0 | phosphorylation | up-regulates activity | 0.393 | Our data demonstrate that gastrin-stimulated PKD2 activation involves a heterotrimeric G alpha(q) protein as well as the activation of phospholipase C. Furthermore, we show that PKD2 can be activated by classical and novel members of the protein kinase C (PKC) family such as PKC alpha, PKC epsilon, and PKC eta.|The position of PKD2 phosphorylated at Ser876 and Ser706/Ser710 is indicated by anarrowhead. | SIGNOR-275955 |
P35354 | Q12968 | 0 | transcriptional regulation | up-regulates quantity by expression | 0.279 | NFAT induces the transcription of the COX2 (cyclo-oxygenase-2) gene incancer cells thereby enhancing invasive migration | SIGNOR-264028 |
P68400 | P05549 | 1 | phosphorylation | up-regulates | 0.307 | Ck2 phosphorylates ap-2_ and increases its transcriptional activity | SIGNOR-175130 |
P13726 | Q16539 | 0 | phosphorylation | down-regulates | 0.291 | We previously showed that the phosphorylation of ser253 within the cytoplasmic domain of human tissue factor (tf) initiates the incorporation and release of this protein into cell-derived microparticles. Furthermore, subsequent phosphorylation of ser258 terminates this process. Our current study has identified p38_ as a major kinase, responsible for the phosphorylation of ser258 within the cytoplasmic domain of tf | SIGNOR-199868 |
P28562 | P54646 | 0 | phosphorylation | down-regulates quantity by destabilization | 0.273 | Taken together, these results imply that nicotine acts via AMPKα2 to phosphorylate MKP1 at Ser334, instigating MKP1 ubiquitination and proteasome-mediated degradation. | SIGNOR-276890 |
Q02224 | P33981 | 0 | phosphorylation | up-regulates activity | 0.43 | Strikingly, phosphorylation of Cenp-E C tail by wild-type (WT) MPS1 or CDK1-cyclin B completely reverses its inhibitory effect toward Cenp-E motor ATPase in solution. | SIGNOR-278999 |
Q05195 | Q9UBS0 | 0 | phosphorylation | down-regulates | 0.2 | In this study, we showed that mad1 is a substrate of p90 ribosomal kinase (rsk) and p70 s6 kinase (s6k). Both rsk and s6k phosphorylate serine 145 of mad1 upon serum or insulin stimulation. Ser-145 phosphorylation of mad1 accelerates the ubiquitination and degradation of mad1 through the 26s proteasome pathway | SIGNOR-178594 |
P04150 | P35575 | 1 | 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-256104 |
P69891 | P17509 | 0 | transcriptional regulation | down-regulates quantity by repression | 0.2 | HOXB6 protein represses globin transcript levels in stably transfected K562 cells in a DNA-binding dependent fashion. | SIGNOR-261638 |
O14827 | P60953 | 1 | guanine nucleotide exchange factor | up-regulates activity | 0.554 | 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-260575 |
Q92995 | Q86U44 | 0 | post transcriptional regulation | up-regulates quantity by stabilization | 0.2 | Furthermore, N6-methyladenosine methyltransferase-like 3 (METTL3) mediated stabilization of USP13 mRNA that required the m6A reader IGF2BP2. | SIGNOR-275839 |
P35568 | Q9Y237 | 0 | isomerization | up-regulates activity | 0.2 | In this study, the association of Par14 with insulin receptor substrate 1 (IRS-1) was demonstrated in HepG2 cells|Therefore, although Pin1 and Par14 associate with different portions of IRS-1, the prolyl cis/trans isomerization in multiple sites of IRS-1 by these isomerases appears to be critical for efficient insulin receptor-induced IRS-1 phosphorylation|Par14 overexpression in HepG2 markedly enhanced insulin-induced IRS-1 phosphorylation and its downstream events | SIGNOR-265756 |
P61586 | Q9UNA1 | 0 | gtpase-activating protein | down-regulates activity | 0.629 | 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-260481 |
P12830 | O60315 | 0 | transcriptional regulation | down-regulates quantity by repression | 0.487 | SIP 1 downregulates mammalian E-cadherin transcription via binding to both conserved E2 boxes of the minimal E-cadh promoter.SIP1 induction resulted in the loss of cell-cell adhesion, in activation of invasion and in at random, multidirectional migration instead of unidirectional coherent migration (required in neurulation). | SIGNOR-268950 |
P51787 | Q13557 | 0 | phosphorylation | down-regulates activity | 0.2 | CaMKII regulates KCNQ1 at S484 during sustained β-AR stimulation to inhibit IKs. The ability of CaMKII to inhibit IKs may contribute to arrhythmogenicity during HF. | SIGNOR-275479 |
P06213 | P17706 | 0 | dephosphorylation | down-regulates | 0.622 | Finally, we have tested the set of ptps for their ability to dephosphorylate a phosphopeptide corresponding to the irk autophosphorylation site. tc-ptp, sap-1, and ptp-1b all tested positive, but ptp-? Showed no activity, although the same gst-ptp preparation could efficiently convert pnpp (tablei). Interestingly, many other ptps showed activity, namely dep-1, glepp-1, lar, ptp-?, -?, -?, And shp-1. | SIGNOR-75914 |
Q13131 | Q9GZY8 | 1 | phosphorylation | up-regulates activity | 0.2 | A screen for substrates of AMPK identified mitochondrial fission factor (MFF), a mitochondrial outer-membrane receptor for DRP1, the cytoplasmic guanosine triphosphatase that catalyzes mitochondrial fission. | SIGNOR-245953 |
P45983 | Q07817 | 1 | phosphorylation | down-regulates | 0.775 | By site-directed mutagenesis studies, we have identified that serine 62 is the necessary site for taxol- or 2-me-induced bcl-xl phosphorylation in prostate cancer cells. Further studies with the inhibitor of jun kinase (jnk) and phosphorylation mutant of bcl-xl reveal the augmentative role of jnk-mediated bcl-xl phosphorylation in apoptosis of prostate cancer cells. In summary, our studies suggest that the phosphorylation of bcl-xl by stress response kinase signaling might oppose the anti-apoptotic function of bcl-xl to permit prostate cancer cells to die by apoptosis | SIGNOR-99219 |
Q92831 | Q15796 | 1 | acetylation | up-regulates | 0.578 | We demonstrate that both smad2 and smad3 are acetylated by the coactivators p300 and cbp in a tgfbeta-dependent manner. Smad2 is also acetylated by p/caf. The acetylation of smad2 was significantly higher than that of smad3. Lys(19) in the mh1 domain was identified as the major acetylated residue in both the long and short isoform of smad2.....acetylation of the short isoform of smad2 improves its dna binding activity in vitro and enhances its association with target promoters in vivo, thereby augmenting its transcriptional activity | SIGNOR-150273 |
P00519 | Q9Y6W5 | 1 | phosphorylation | up-regulates activity | 0.698 | Furthermore, Abl phosphorylates WAVE2 on tyrosine 150, and WAVE2 deficient cells rescued with a Y150F mutant fail to regain their ability to ruffle and form microspikes, unlike cells rescued with wild-type WAVE2.|Together, these data show that c-Abl activates WAVE2 via tyrosine phosphorylation to promote actin remodeling in vivo and that Abi-1 forms the crucial link between these two factors. | SIGNOR-279390 |
P17676 | P24941 | 0 | phosphorylation | up-regulates | 0.395 | Mass spectrometric analysis revealed that cdk2/cyclina phosphorylates c/ebpbeta on thr(188) and is required for phosphorylation (on ser(184) or thr(179)) of c/ebpbeta by gsk3beta and maintenance of dna binding activity. | SIGNOR-196372 |
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 |
P68400 | Q14005 | 1 | phosphorylation | up-regulates activity | 0.326 | We now show that N-terminal to the NLS domain of pro-IL-16 are protein kinase CK2 substrate and cdc2 kinase substrate sites which, along with the NLS, constitute a dual phosphorylation-regulated CcN motif which regulates nuclear localization of pro-IL-16. In addition, we demonstrate that mutation of either site is associated with impairment of the N-terminal domain's ability to induce G(0)/G(1) cell cycle arrest. | Thus, we confirm that the N-terminal (42SLNEE46) sequence of pro-IL-16 is in fact a site for protein kinase CK2 phosphorylation. | SIGNOR-250905 |
P56178 | Q16539 | 0 | phosphorylation | up-regulates activity | 0.291 | We show that Dlx5 is a novel substrate for p38 MAPK in vitro and in vivo and that Ser-34 and Ser-217 are the sites phosphorylated by p38 | SIGNOR-255792 |
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 |
P24941 | O43379 | 0 | relocalization | up-regulates activity | 0.244 | Primary microcephaly (MCPH) associated proteins CDK5RAP2, CEP152, WDR62 and CEP63 colocalize at the centrosome. We found that they interact to promote centriole duplication and form a hierarchy in which each is required to localize another to the centrosome, with CDK5RAP2 at the apex, and CEP152, WDR62 and CEP63 at sequentially lower positions. MCPH proteins interact with distinct centriolar satellite proteins; CDK5RAP2 interacts with SPAG5 and CEP72, CEP152 with CEP131, WDR62 with MOONRAKER, and CEP63 with CEP90 and CCDC14. These satellite proteins localize their cognate MCPH interactors to centrosomes and also promote centriole duplication. Consistent with a role for satellites in microcephaly, homozygous mutations in one satellite gene, CEP90, may cause MCPH. The satellite proteins, with the exception of CCDC14, and MCPH proteins promote centriole duplication by recruiting CDK2 to the centrosome. | SIGNOR-271726 |
P49675 | P36776 | 0 | cleavage | down-regulates quantity by destabilization | 0.268 | Turnover of mitochondrial steroidogenic acute regulatory (StAR) protein by Lon protease: the unexpected effect of proteasome inhibitors | SIGNOR-265726 |
P12931 | Q9Y613 | 1 | phosphorylation | up-regulates activity | 0.306 | Our results show that only Src can efficiently phosphorylate FHOD1 at Y99 to enable the downstream activation by ROCK. | SIGNOR-276612 |
O00206 | Q9NWF9 | 0 | ubiquitination | down-regulates quantity by destabilization | 0.388 | Here we describe how a RING finger protein, Triad3A, acts as an E3 ubiquitin-protein ligase and enhances ubiquitination and proteolytic degradation of some TLRs. Triad3A overexpression promoted substantial degradation of TLR4 and TLR9 with a concomitant decrease in signaling, but did not affect TLR2 expression or signaling. | SIGNOR-271504 |
P63000 | P35125 | 1 | relocalization | up-regulates | 0.338 | In quiescent cells, tre17 is localized to intracellular filamentous and punctate structures in the cytoplasm, folded in an inactive conformation. Upon growth factor addition, cdc42 and rac1 become activated and recruit tre17 to the plasma membrane. Stable membrane localization of tre17 also requires polymerized actin. This recruitment process leads to a conformational change in tre17, such that the n-terminal portion of the molecule further stimulates the accumulation of cortical actin. | SIGNOR-98938 |
Q8TD19 | Q9GZQ8 | 1 | phosphorylation | down-regulates activity | 0.2 | LC3B is phosphorylated at Thr-50 within the LDS by serine/threonine kinase (STK) 3 and STK4. Here, we identified LIR motifs in STK3 and atypical protein kinase Cζ (PKCζ) and never in mitosis A (NIMA)-related kinase 9 (NEK9). All three kinases phosphorylated LC3B Thr-50 in vitro A phospho-mimicking substitution of Thr-50 impaired binding of several LIR-containing proteins, such as ATG4B, FYVE, and coiled-coil domain-containing 1 (FYCO1), and autophagy cargo receptors p62/sequestosome 1 (SQSTM1) and neighbor of BRCA1 gene (NBR1). | SIGNOR-273904 |
P53671 | Q99801 | 1 | phosphorylation | down-regulates activity | 0.2 | LIMK2 also downregulates NKX3.1 mRNA levels.|While WT-NKX3.1 was efficiently phosphorylated, the S185A mutant showed no phosphorylation ( xref A), confirming that LIMK2 only phosphorylates the S185 site in NKX3.1. | SIGNOR-278951 |
Q15139 | Q8WYL5 | 1 | phosphorylation | down-regulates | 0.479 | Pkd-mediated phosphorylation of serines 937 and 978 regulates ssh1l subcellular localization by binding of 14-3-3 proteins 14-3-3 proteins associate with ssh1l when phosphorylated at serines 937 and 978, thereby sequestering ssh1l in the cytoplasm and preventing translocation of the phosphatase to f-actin_rich membrane protrusions | SIGNOR-186471 |
Q9UQL6 | Q9BZL6 | 0 | phosphorylation | up-regulates activity | 0.295 | Histone deacetylase (HDAC) 5 and 7, two members of the class II of classical HDAC [62], are in vivo substrates of PKD3 and PKD [63]. In response to a variety of signals, including phorbol esters, T cell receptor engagement, vascular endothelial growth factor and angiotensin stimulation, the activity of HDAC5 and 7 are regulated by a mechanism that involves PKD3 and PKD-mediated phosphorylation of the highly conserved Ser259 and Ser498 residues that are located in N-terminus of class II HDACs [63–67]. | SIGNOR-275929 |
Q9P0W2 | O15344 | 0 | polyubiquitination | down-regulates quantity by destabilization | 0.244 | The E3 ubiquitin ligase MID1/TRIM18 promotes atypical ubiquitination of the BRCA2-associated factor 35, BRAF35. MID1 is implicated in BRAF35 ubiquitination promoting atypical poly-ubiquitination via K6-, K27- and K29-linkages. We found that MID1 depletion alters BRAF35 localization in these structures and increases BRAF35 stability affecting its cytoplasmic abundance | SIGNOR-272317 |
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