IdA string | IdB string | labels int64 | mechanism string | effect string | score float64 | sentence string | signor_id string |
|---|---|---|---|---|---|---|---|
P06493 | P49459 | 1 | phosphorylation | up-regulates | 0.37 | Hhr6a is phosphorylated in vitro by cdk-1 and -2 on ser120, a residue conserved in all hhr6a homologues, resulting in a 4-fold increase in its ubiquitin-conjugating activity. | SIGNOR-116504 |
O96004 | Q15797 | 0 | transcriptional regulation | up-regulates quantity | 0.2 | Chromatin immunoprecipitation (ChIP) revealed a subset of the BIG (BMP4 induced genes) signature, including Satb2, Smad6, Hand1, Gadd45γ and Gata3, that was bound by Smad1/5 in the developing mandible, revealing direct Smad-mediated regulation | SIGNOR-268936 |
P62330 | Q99418 | 0 | guanine nucleotide exchange factor | up-regulates activity | 0.887 | Effects of ARNO upon Axonogenesis Are Mediated by Downstream Activation of ARF6. ARNO/ARF6 signaling pathways that could modulate actin reorganization in the axonal growth cone. ARNO stimulates GTP exchange on ARF6, thereby increasing the amount of active ARF6. | SIGNOR-264910 |
P17252 | Q96T49 | 1 | phosphorylation | down-regulates activity | 0.2 | PKCα phosphorylated the full length recombinant TIMAP in in vitro kinase assay and Ser331 of TIMAP was shown to be phosphorylated by PKC. Phosphorylation of TIMAP upon PKC activation in endothelial cells results in enrichment of TIMAP in the membrane, but no such change can be observed in PKC depleted cells. Phosphorylation state of TIMAP, through affecting PP1 activity, has a remarkable effect on endothelial barrier function. | SIGNOR-273802 |
Q92630 | O43255 | 1 | phosphorylation | up-regulates | 0.41 | In the present study, we identify the serine/threonine kinase dyrk2 as siah2 interaction partner that phosphorylates siah2 at five residues (ser16, thr26, ser28, ser68, and thr119). accordingly, phosphorylated siah2 is more active than the wild-type e3 ligase and shows an increased ability to trigger the hif-1?-Mediated transcriptional response and angiogenesis. | SIGNOR-198729 |
Q16665 | P28482 | 0 | phosphorylation | up-regulates | 0.586 | We show that at least two different nuclear protein kinases, one of them identified as p42/p44 mapk, can modify hif-1_. Analysis of in vitro phosphorylated hif-1_ by mass spectroscopy revealed residues ser-641 and ser-643 as possible mapk phosphorylation sites these data suggest that phosphorylation of ser-641/643 by mapk promotes the nuclear accumulation and transcriptional activity of hif-1_ | SIGNOR-178723 |
O43683 | Q12834 | 1 | phosphorylation | down-regulates activity | 0.992 | Bub1 directly phosphorylates Cdc20 in vitro and inhibits the ubiquitin ligase activity of APC/C(Cdc20) catalytically. A Cdc20 mutant with all six Bub1 phosphorylation sites removed is refractory to Bub1-mediated phosphorylation and inhibition in vitro. | SIGNOR-250606 |
Q13177 | P49593 | 0 | dephosphorylation | down-regulates | 0.261 | Pop x2, a pp 2c serine/threonine phosphatase, is known to dephosphorylate pak and downregulate its activity. | SIGNOR-162149 |
Q9NYV4 | P24928 | 1 | phosphorylation | up-regulates activity | 0.784 | Cyck/cdk12 can activate transcription and phosphorylate ser2 in the ctd of rnapii / phosphorylation of serine at position 2 (ser2) is thought to be responsible for productive transcriptional elongation and synthesis of full-length mature mrna | SIGNOR-176805 |
Q13315 | P48730 | 1 | phosphorylation | up-regulates activity | 0.34 | These results elucidated the specificity of this in vivo degradation assay, and further implicated that CKI\u03b4-dependent phosphorylation events is the major signaling route through which DNA damage-dependent activation of ATM might control timely turnover of Mdm2 during genotoxic stress. (A) ATM-mediated phosphorylation of CK1\u03b4 promotes CK1\u03b4 nuclear localization.|We further demonstrated that DNA damage-induced activation of ATM directly phosphorylated CKI\u03b4 at two well-conserved S/TQ sites, which promotes CKI\u03b4 nuclear localization to increase CKI\u03b4-mediated phosphorylation of Mdm2, thereby facilitating subsequent Mdm2 ubiquitination by SCF\u03b2-TRCP. | SIGNOR-279504 |
P10071 | P17612 | 0 | phosphorylation | down-regulates quantity | 0.468 | Ci/gli zinc finger proteins mediate the transcriptional effects of hedgehog protein signals. In drosophila, ci action as transcriptional repressor or activator is contingent upon hedgehog-regulated, pka-dependent proteolytic processingall six pka phosphorylation sites are required for processing of gli3. | SIGNOR-75359 |
P46934 | Q00987 | 1 | ubiquitination | up-regulates quantity by stabilization | 0.466 | NEDD4 promotes MDM2 ubiquitination in a dose- and time-dependent manner, whereas depletion of NEDD4 reduced the half-life of endogenous MDM2 [ xref ]. | SIGNOR-278769 |
P07333 | Q9H334 | 0 | transcriptional regulation | down-regulates quantity by repression | 0.296 | Overexpression of MFH/Foxp1 markedly attenuated phorbol ester-induced expression of c-fms, which encodes the M-CSF receptor and is obligatory for macrophage differentiation. | SIGNOR-269048 |
P46783 | O96006 | 0 | transcriptional regulation | up-regulates quantity by expression | 0.2 | HDRE-like sequences act as positive regulatory elements for RP gene promoter activities in vivo. | Cotransfection of a plasmid expressing hDREF increased luciferase expression directed by each RP gene promoter more than 30% compared with the values obtained without the hDREF-expressing plasmid. | SIGNOR-266083 |
O96013 | P17676 | 1 | phosphorylation | up-regulates activity | 0.2 | Importantly, we found that PAK4 enhanced CEBPB phosphorylation on Thr 235.|In summary, we showed that PAK4 mediated CEBPB activation upregulated CLDN4 expression to promote breast cancer cell migration and invasion. | SIGNOR-280055 |
P27361 | Q15788 | 1 | phosphorylation | up-regulates | 0.268 | Mapk also directly phosphorylates src-1 at thr1179 and ser1185. Phosphorylation of src-1 by mitogen-activated protein kinase (mapk) is required for optimal progesterone receptor-dependent transcription and for functional cooperation with camp response element-binding protein-binding protein | SIGNOR-91143 |
Q15910 | P31269 | 1 | transcriptional regulation | down-regulates quantity by repression | 0.396 | These data support the proposed regulatory impact of particular PRC2-proteins in expression of HOXA9 and HOXA10 in NK/T-cells. In mammalian cells knockdown of PRC2 components EZH2 or PHF1 led to upregulated HOXA gene expression. | SIGNOR-260068 |
Q96JC1 | Q13485 | 1 | relocalization | down-regulates activity | 0.318 | The data demonstrating binding of TLP to TGF-β and activin type II receptors and selective inhibition of Smad3/Smad4 complex formation by deregulated TLP suggest that TLP is involved in localizing these receptors and Smad4 to specific intracellular compartments, where it regulates formation of Smad3/Smad4 but not Smad2/Smad4 complexes. | SIGNOR-261377 |
O14920 | P12931 | 0 | phosphorylation | up-regulates | 0.362 | These results indicate that c-src can associate with ikkbeta and phosphorylate its tyrosine residues after tnf-alfa or tpa stimulation. | SIGNOR-99318 |
P09651 | P17252 | 0 | phosphorylation | down-regulates | 0.2 | A survey of seven protein kinases showed that a1 was heavily phosphorylated by protein kinase c (pkc) and also was phosphorylated by casein kinase iiamino acid sequencing revealed that these sites were ser95, ser192, and ser199;phosphorylation at ser192 was more abundant than at ser95 and ser199. Phosphorylation by pkc inhibited the strand annealing activity of a1. | SIGNOR-32291 |
P19174 | Q06187 | 0 | phosphorylation | up-regulates activity | 0.581 | Then, BTK and ITK are activated by Src kinases and proceed to phosphorylate the lipase PLCgamma2 / PLCgamma1, which cleaves PIP2 in the plasma membrane and generates the secondary messengers IP3 and DAG. | SIGNOR-279444 |
P26045 | P03372 | 1 | dephosphorylation | up-regulates activity | 0.2 | Our recent studies further demonstrated that PTPH1 dephosphorylates estrogen receptor at Y537, increases estrogen receptor stability and nuclear accumulation, and enhances breast cancer sensitivity to anti-estrogens [ ]. | SIGNOR-277127 |
Q13485 | Q92905 | 0 | ubiquitination | down-regulates | 0.433 | We report a novel mechanism of smad4 degradation. Jab1 interacts directly with smad4 and induces its ubiquitylation for degradation | SIGNOR-114697 |
Q13158 | Q9BV47 | 0 | dephosphorylation | down-regulates activity | 0.366 | This multi-functionality of fadd may depend primarily on its subcellular location. Fadd shuttles between the cytosol and the nucleus and this signal is unclear;however, fadd trafficking requires phosphorylation of the protein on ser194dusp26 suppresses cell proliferation by fadd dephosphorylation | SIGNOR-204559 |
O60260 | O43236 | 1 | ubiquitination | down-regulates quantity by destabilization | 0.2 | Thus, Parkin degrades ARTS in a proteasome dependent manner.|Together, these results suggest that Parkin specifically ubiquitinates and degrades ARTS, and that this degradation may be linked to the pro-apoptotic function of ARTS. | SIGNOR-278642 |
Q03933 | P35227 | 0 | sumoylation | down-regulates activity | 0.325 | MEL-18, in contrast to the polycomb protein PC2/CBX4, in which SUMO E3 activity stimulates sumoylation of certain proteins, actually functions like an anti-SUMO E3 protein, interacting with both HSF2 and the SUMO E2 UBC9 but acting to inhibit UBC9 activity and thereby decreasing sumoylation of a target protein, in this case that of HSF2. sumoylation of HSF2 is up-regulated during mitosis and is important for the interaction of this factor with a subunit of the condensin complex during the bookmarking process | SIGNOR-226245 |
Q9Y4A8 | P15559 | 1 | transcriptional regulation | down-regulates quantity by repression | 0.338 | Deletion mutation analysis revealed that Nrf3 repression of NQO1 gene expression required heterodimerization and DNA binding domains but not transcriptional activation domain of Nrf3. | SIGNOR-268976 |
Q9NQC7 | P20749 | 1 | deubiquitination | down-regulates | 0.512 | Cyld binds and deubiquitinates bcl-3in cyld+/+ keratinocytes, tpa or uv light triggers the translocation of cyld from the cytoplasm to the perinuclear region, where cyld binds and deubiquitinates bcl-3, thereby preventing nuclear accumulation of bcl-3 and p50/bcl-3- or p52/bcl-3-dependent proliferation. | SIGNOR-146774 |
P61586 | P35241 | 1 | phosphorylation | up-regulates activity | 0.47 | Rev-erbα interacted with OPHN-1, promoted RhoA activity and phosphorylation of ERM. etection of phosphorylated ezrin (Thr567)/radixin (Thr564)/moesin (Thr558)(p-ERM) in Rev-erbαfl/flCre− and Rev-erbαfl/flPF4Cre+ platelets using phospho-specific antibodies. | SIGNOR-268430 |
Q14012 | O00429 | 1 | phosphorylation | up-regulates activity | 0.333 | For example, protein kinase A (PKA) phosphorylation of Drp1S600 has been reported to decrease Drp1 GTPase activity in vitro (23, 24), whereas phosphorylation of the same conserved serine residue by Ca2+-calmodulin–dependent protein kinase Iα (CaMKIα) in Drp1 isoform 3 has been reported to cause a significant increase in mitochondrial fission | SIGNOR-262552 |
P09471 | P19474 | 1 | null | down-regulates | 0.2 | Mechanistically, GNAO1 recruited TRIM21 and facilitated TRIM21-mediated ubiquitination. | SIGNOR-278888 |
O00311 | O75475 | 1 | phosphorylation | up-regulates | 0.334 | We now report identification of the cdc7-activator of s-phase kinase (ask) heterodimer as a novel interactor of ledgf. the kinase phosphorylated ledgf in vitro, with ser-206 being the major target, and ledgf phosphorylated at this residue could be detected during s phase of the cell cycle. Ledgf potently stimulated the enzymatic activity of cdc7-ask, increasing phosphorylation of mcm2 in vitro by more than 10-fold. | SIGNOR-25763 |
Q99683 | Q9UNI6 | 0 | dephosphorylation | down-regulates activity | 0.25 | Our study showed that DUSP12 inhibited ASK1-JNK activation and DUSP12 can directly bind to and dephosphorylate ASK1. | SIGNOR-277032 |
Q12778 | O75874 | 1 | transcriptional regulation | up-regulates quantity by expression | 0.258 | We identify FOXOs as transcriptional activators of IDH1. FOXOs promote IDH1 expression and thereby maintain the cytosolic levels of α-ketoglutarate and NADPH. | SIGNOR-260101 |
Q9BZI1 | P28482 | 0 | phosphorylation | up-regulates activity | 0.2 | We tested the transcriptional properties of Irx2 by dividing it into amino- and carboxy terminal parts and found that Mek1-mediated phosphorylation activates and derepresses the amino and carboxyl parts, respectively. When Ser46 and Ser65 were mutated to alanine (S46A and S65A), phosphorylation was reduced, whereas substitution of Ser83 and Ser103 (S83A and S103A) did not affect phosphorylation. | SIGNOR-263052 |
P28482 | P30041 | 1 | phosphorylation | up-regulates | 0.693 | These results show that the mapks can mediate phosphorylation of prdx6 at thr-177 with a consequent marked increase in its aipla(2) activity. | SIGNOR-183379 |
Q13627 | P49418 | 1 | phosphorylation | down-regulates | 0.396 | Recent studies show that phosphorylation of amphiphysin1 prd by cdk5 inhibited the association of amphiphysin1 with ap-2 in synaptic vesicle endocytosis (7, 8) similar to that by mapk (present report). Cdk5 appears to phosphorylate amphiphysin1 at serines 261, 272, 276, and 285 and threonine 310, located in the prd | SIGNOR-126843 |
Q5S007 | P46734 | 1 | phosphorylation | up-regulates activity | 0.393 | LRRK2 phosphorylates MKK3 and MKK7 in vitro but has a relatively minor effect on MKK6 phosphorylation. | SIGNOR-279057 |
P13051 | O15297 | 0 | dephosphorylation | down-regulates activity | 0.377 | PPM1D dephosphorylation of UNG2 is correlated with reduced UNG2 activity on uracil-containing templates.|This result suggests that PPM1D specifically inhibits UNG2 and not other uracil DNA glycosylases. | SIGNOR-277156 |
P29320 | Q8NBZ7 | 1 | phosphorylation | up-regulates activity | 0.2 | However, it is possible that etk is a principal activator of Ugd.|The phosphorylation of the Ugd protein (a UDP-glucose dehydrogenase) by Etk increases Ugd dehydrogenase activity. | SIGNOR-280006 |
O43541 | P51817 | 0 | phosphorylation | up-regulates activity | 0.431 | In vitro phosphorylation assays demonstrated that PrKX phosphorylates Smad6 at a serine residue. | SIGNOR-279270 |
Q13535 | Q9NZC9 | 1 | phosphorylation | down-regulates activity | 0.538 | ATR phosphorylates SMARCAL1 on S652, thereby limiting its fork regression activities and preventing aberrant fork processing. Thus, phosphorylation of SMARCAL1 is one mechanism by which ATR prevents fork collapse, promotes the completion of DNA replication, and maintains genome integrity. | SIGNOR-273516 |
P18887 | P19784 | 0 | phosphorylation | up-regulates activity | 0.46 | XRCC1 is phosphorylated in vivo and in vitro by CK2, and CK2 phosphorylation of XRCC1 on S518, T519, and T523 largely determines aprataxin binding to XRCC1 though its FHA domain | In addition, we present data to show that the acute loss of aprataxin by small interfering RNA (siRNA) renders HeLa cells sensitive to MMS through a mechanism that destabilizes XRCC1. | SIGNOR-251050 |
P24385 | Q96PU4 | 0 | ubiquitination | down-regulates quantity by destabilization | 0.294 | We found that NIRF directly ubiquitinated cyclins D1 and E1, as evidenced by the appearance of the tail (Fig. 4B). In summary, the above findings suggest that NIRF tightly cooperates with the core cell cycle machinery and induces G1 arrest, which is accompanied by ubiquitination of cyclins D1 and E1. | SIGNOR-271885 |
O43521 | P27361 | 0 | phosphorylation | down-regulates quantity by destabilization | 0.731 | In vitro, bimel was phosphorylated by extracellular signal-regulated kinase on ser(69), which resides in the bimel-specific insert region. Using phosphospecific antibody against this site, we show that this residue is actually phosphorylated in cells. We also show that phosphorylation of ser(69) promotes ubiquitination of bimel. We conclude that mek inhibitors sensitize mda-mb231 and hbc4 cells to anoikis by blocking phosphorylation and hence degradation of bimel | SIGNOR-129878 |
P12882 | Q14814 | 0 | transcriptional regulation | up-regulates quantity by expression | 0.34 | 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-238751 |
Q00535 | P21860 | 1 | phosphorylation | up-regulates activity | 0.341 | We demonstrated that Cdk5 phosphorylated Ser-1176 in the neuregulin receptor ErbB2 and phosphorylated Thr-871 and Ser-1120 in the ErbB3 receptor. We identified the Ser-1120 sequence RSRSPR in ErbB3 as a novel phosphorylation consensus sequence of Cdk5. Finally, we found that Cdk5 activity is involved in neuregulin-induced Akt activity and neuregulin-mediated neuronal survival. | SIGNOR-250663 |
Q92985 | Q9Y4K3 | 0 | ubiquitination | up-regulates activity | 0.732 | We have shown that TRAF6 E3 ligase promotes IRF7 K63-linked ubiquitination that is required for EBV LMP1 activation of IRF7 [ xref ]; however, A20, a member with both E3 ligase and deubiquitinase activities in the OTU family, inhibits LMP1-stimulated IRF7 activity by acting as a deubiquitinase [ xref ]. | SIGNOR-278788 |
P17676 | P28482 | 0 | phosphorylation | up-regulates | 0.716 | Phosphorylation of cebpb at thr(235) peaked at 16 hours in il-1beta-stimulated cells. The mek inhibitor u0126 inhibited this phosphorylation and reduced mmp-1 gene induction. | SIGNOR-187798 |
P62136 | Q9BYX4 | 1 | dephosphorylation | up-regulates activity | 0.2 | Exogenous PP1alpha or PP1gamma substantially decreased the S88 phosphorylation of Flag-MDA5|we identified PP1alpha and PP1gamma as primary phosphatases responsible for MDA5 and RIG-I dephosphorylation, leading to their activation. | SIGNOR-264577 |
Q13085 | Q9NP71 | 0 | transcriptional regulation | up-regulates quantity by expression | 0.435 | The present study provides evidence for a direct and dominant role of ChREBP in the glucose regulation of two key liver lipogenic enzymes, acetyl-CoA carboxylase (ACC) and fatty acid synthase (FAS) | SIGNOR-267946 |
P00519 | P46527 | 1 | phosphorylation | down-regulates quantity | 0.595 | A conserved tyrosine residue (Y88) in the Cdk-binding domain of p27 can be phosphorylated by the Src-family kinase Lyn and the oncogene product BCR-ABL | SIGNOR-245293 |
O15117 | P06241 | 0 | phosphorylation | up-regulates activity | 0.2 | two tyrosines, Tyr595 and Tyr651, of FYB are major sites of phosphorylation by FYN-T and mediate binding to SLP-76 in Jurkat T cells. We further demonstrate that the loss of SLP-76 binding by mutation of these sites markedly reduced the ability of FYN-T-FYB-SLP-76 to up-regulate IL-2 transcription. | SIGNOR-251163 |
Q13322 | P42345 | 0 | phosphorylation | up-regulates | 0.412 | The adaptor protein grb10 was identified as an mtorc1 substrate that mediates the phosphoinositide 3-kinase. | SIGNOR-174071 |
Q15418 | P19634 | 1 | phosphorylation | up-regulates | 0.452 | The results indicate that p90rsk phosphorylates serine 703 of nhe-1, and this phosphorylation is required for growth factor stimulation of na+/h+ exchange. | SIGNOR-69171 |
Q9H410 | Q8IWV8 | 0 | ubiquitination | down-regulates quantity | 0.2 | Mub1 and Ubr2 mediate Dsn1 ubiquitylation and degradation.|The levels of WT Dsn1 were also increased in the mub1Delta and ubr2Delta strains, suggesting that Mub1 and Ubr2 mediate the degradation of WT Dsn1 protein. | SIGNOR-278795 |
P48729 | O00257 | 1 | phosphorylation | down-regulates quantity by destabilization | 0.2 | The phosphorylation of CBX4 at T437 by casein kinase 1α (CK1α) facilitated its ubiquitination at both K178 and K280 and subsequent degradation by CHIP, and this phosphorylation of CBX4 could be reduced by TNFα. | SIGNOR-277512 |
P05455 | P68400 | 0 | phosphorylation | up-regulates | 0.337 | Prior studies indicate that hla is activated by phosphorylation of serine-366 by protein kinase ck2, neutralizing a negative effect of a short basic motif (sbm) | SIGNOR-160761 |
O14920 | P19838 | 1 | phosphorylation | down-regulates quantity by destabilization | 0.853 | Ikkbeta phosphorylates p105 resulting in its degradation, which releases tpl2 resulting in activation of the pro-proliferative map kinase- pathway. | SIGNOR-70473 |
P52954 | O95863 | 1 | transcriptional regulation | up-regulates quantity by expression | 0.32 | Compared with the empty vector, LBX1 induced increased promoter activity of threefold to fourfold and fivefold to sixfold for ZEB1 and Snail1, respectively | SIGNOR-266053 |
P00533 | P09874 | 1 | phosphorylation | up-regulates activity | 0.394 | EGFR and MET heterodimer interacts with and phosphorylates PARP1. | SIGNOR-279169 |
Q9HC77 | O00444 | 0 | phosphorylation | up-regulates | 0.799 | Plk2 phosphorylates the s589 and s595 residues of cpap in vitro and in vivo. This phosphorylation is critical for procentriole formation during the centrosome cycle. Plk4 also phosphorylates s595 of cpap | SIGNOR-166007 |
P21127 | O96017 | 0 | phosphorylation | up-regulates activity | 0.2 | CHK2 kinase promotes pre-mRNA splicing via phosphorylating CDK11p110|Unexpectedly, CHK2 kinase constitutively phosphorylated CDK11(p110) in a DNA damage-independent manner. | SIGNOR-279458 |
Q96GD4 | O95239 | 1 | phosphorylation | up-regulates activity | 0.517 | Using in vitro kinase assays, we found that active AMPK and Aurora B phosphorylated KIF4A at Ser801 and Thr799 respectively in a time-dependent manner (Figure 5D). KIF4A is phosphoregulated by AMPK and Aurora B. Although AMPK phosphorylation increased the ATPase activity of KIF4A, Aurora B phosphorylation resulted in a stronger increase (Figure 5I), which might be consistent with the more powerful kinase function of Aurora B during mitosis. | SIGNOR-265992 |
P20810 | Q8TDC3 | 0 | phosphorylation | up-regulates activity | 0.2 | Here, we show that an AZ cytomatrix protein CAST and an AZ-associated protein kinase SAD-B coordinately regulate STD by controlling reloading of the AZ with release-ready synaptic vesicles. SAD-B phosphorylates the N-terminal serine (S45) of CAST, and S45 phosphorylation increases with higher firing rate. | SIGNOR-263051 |
Q02750 | O15530 | 0 | phosphorylation | up-regulates activity | 0.27 | In vitro kinase assay revealed that the direct targets of pdk1 in the mapk pathway were the upstream mapk kinases mek1 and mek2. The identified pdk1 phosphorylation sites in mek1 and mek2 are ser222 and ser226, respectively, and are known to be essential for full activation | SIGNOR-236633 |
P60953 | Q96P48 | 0 | gtpase-activating protein | down-regulates activity | 0.531 | 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-260452 |
P52789 | P01106 | 0 | transcriptional regulation | up-regulates quantity | 0.37 | Here, using the P493-6 Burkitt's lymphoma model with an inducible MYC, we demonstrate that HIF-1 cooperates with dysregulated c-Myc to promote glycolysis by induction of hexokinase 2, which catalyzes the first step of glycolysis, and pyruvate dehydrogenase kinase 1, which inactivates pyruvate dehydrogenase and diminishes mitochondrial respiration. | SIGNOR-259986 |
P14373 | O75385 | 1 | ubiquitination | down-regulates quantity | 0.2 | STK38L ubiquitination promotes its activation and phosphorylation of ULK1 at Ser495, rendering ULK1 in a permissive state for TRIM27-mediated hyper-ubiquitination | SIGNOR-270349 |
P15172 | Q09472 | 0 | acetylation | up-regulates | 0.681 | Our results provide direct evidence that myod acetylation functionally activates the protein and show that both pcaf and cbp/p300 are candidate enzymes for myod acetylation in vivo. | SIGNOR-81053 |
Q15746 | P28482 | 0 | phosphorylation | up-regulates activity | 0.478 | Inhibition of ERK2 impaired phosphorylation of MLCK and insulin stimulated glucose uptake.|These findings suggest that ERK2 activates MLCK which then mediates the phosphorylation of RLC of MyoIIA. | SIGNOR-279226 |
P84077 | Q9Y6D6 | 0 | guanine nucleotide exchange factor | up-regulates activity | 0.6 | Brefeldin A-inhibited guanine nucleotide-exchange protein 1 (BIG1) is an approximately 200-kDa brefeldin A-inhibited guanine nucleotide-exchange protein that preferentially activates ADP-ribosylation factor 1 (ARF1) and ARF3. | SIGNOR-272147 |
Q16621 | Q96J02 | 0 | ubiquitination | down-regulates activity | 0.413 | Itch regulates p45/NF-E2 in vivo by Lys63-linked ubiquitination| Interestingly, Itch suppressed the transactivation activity of p45/NF-E2 by adding a Lys63-linked polyubiquitin chain. Confocal microscopy revealed that ubiquitinated p45/NF-E2 became localized in the cytoplasm when Itch was over-expressed. Thus, Itch-mediated ubiquitination of p45/NF-E2 does not target the protein for proteasomal degradation, but instead retains p45/NF-E2 in the cytoplasm, where it cannot function as a transactivator. | SIGNOR-275553 |
P42229 | P18031 | 0 | dephosphorylation | down-regulates activity | 0.676 | A Cytosolic Protein-tyrosine Phosphatase PTP1B Specifically Dephosphorylates and Deactivates Prolactin-activated STAT5a and STAT5b | SIGNOR-248428 |
Q13153 | P16949 | 1 | phosphorylation | down-regulates | 0.374 | The hgf-induced wave2 transport, lamellipodia formation, stathmin/op18 phosphorylation at ser38 and binding to kinesin-wave2 complex, but not stathmin/op18 phosphorylation at ser25 and microtubule growth, were abrogated by pak1 inhibitor ipa-3 | SIGNOR-183503 |
P20340 | O43896 | 0 | relocalization | up-regulates quantity | 0.409 | Here, we identify Bicaudal-D-related protein 1 (BICDR-1) as an effector of the small GTPase Rab6 and key component of the molecular machinery that controls secretory vesicle transport in developing neurons. BICDR-1 interacts with kinesin motor Kif1C, the dynein/dynactin retrograde motor complex, regulates the pericentrosomal localization of Rab6-positive secretory vesicles and is required for neural development in zebrafish. In young neurons, BICDR-1 accumulates Rab6 secretory vesicles around the centrosome, restricts anterograde secretory transport and inhibits neuritogenesis. Later during development, BICDR-1 expression is strongly reduced, which permits anterograde secretory transport required for neurite outgrowth. These results indicate an important role for BICDR-1 as temporal regulator of secretory trafficking during the early phase of neuronal differentiation. | SIGNOR-266877 |
P14138 | P23276 | 0 | cleavage | up-regulates activity | 0.676 | These data demonstrate that the Kell blood group protein is a proteolytic enzyme that processes big ET-3, generating ET-3, a potent bioactive peptide with multiple biological roles. | SIGNOR-256354 |
O60729 | P25054 | 1 | dephosphorylation | up-regulates | 0.2 | The phosphatase cdc14b translocates from the nucleolus to the nucleoplasm and induces the activation of the ubiquitin ligase apc/ccdh1 | SIGNOR-179636 |
Q9BY78 | Q13501 | 1 | ubiquitination | up-regulates activity | 0.358 | SQSTM1 Is a Substrate for RNF26 and the DUB USP15. Catalytically competent RNF26 (light red) recruits SQSTM1 (blue) and mediates ubiquitin ligation (red), which serves to attract UBDs of specific vesicle-associated adaptors. | SIGNOR-269830 |
P46459 | P43378 | 0 | dephosphorylation | down-regulates | 0.413 | Our results suggest that the molecular mechanism by which ptp-meg2 promotes secretory vesicle fusion involves the local release of nsf from a tyrosine-phosphorylated, inactive state. | SIGNOR-128348 |
Q13535 | Q8IUQ4 | 1 | phosphorylation | down-regulates activity | 0.2 | We have also demonstrated that DNA damage triggers disruption of the HIPK2-Siah-1 complex, resulting in HIPK2 stabilization and activation. Disruption of the HIPK2-Siah-1 complex is mediated by the ATM/ATR pathway and involves ATM/ATR-dependent phosphorylation of Siah-1 at Ser 19. | SIGNOR-276167 |
P07948 | Q16827 | 0 | dephosphorylation | down-regulates activity | 0.325 | Both Lyn and ZAP70 were dephosphorylated by wild-type PTPROt, but not by its catalytic site mutant.|Lyn kinase and ZAP70 are substrates of PTPROt in B-cells: Lyn inactivation by PTPROt sensitizes leukemia cells to VEGF-R inhibitor pazopanib. | SIGNOR-277144 |
P12272 | P24941 | 0 | phosphorylation | down-regulates | 0.372 | Phosphorylation at the cyclin-dependent kinases site (thr85) of parathyroid hormone-related protein negatively regulates its nuclear localization | SIGNOR-68548 |
P15391 | P00519 | 0 | phosphorylation | up-regulates activity | 0.533 | The results revealed that only tyrosine (Y)490 of CD19 was phosphorylated by c-Abl. | SIGNOR-245283 |
Q8WV44 | P05771 | 1 | polyubiquitination | down-regulates quantity by destabilization | 0.317 | RINCK induces the ubiquitination of PKC both in vitro and in cells. Overexpression of RINCK reduces the levels of PKC in cells, whereas genetic knockdown of endogenous RINCK increases the levels of PKC. The RINCK-mediated ubiquitination is likely to be polyubiquitination, because the ubiquitinated PKCβII was detected as a high molecular weight smear. | SIGNOR-271667 |
Q9HCX3 | P42772 | 1 | transcriptional regulation | down-regulates quantity by repression | 0.28 | Finally, we show that ZNF304 also directs transcriptional silencing of INK4-ARF in human embryonic stem cells. | SIGNOR-266099 |
P09651 | Q13148 | 0 | post transcriptional regulation | up-regulates | 0.406 | TDP-43 regulates the alternative splicing of hnRNP A1 to yield an aggregation-prone variant in amyotrophic lateral sclerosis | SIGNOR-262824 |
P50750 | P10412 | 1 | phosphorylation | down-regulates activity | 0.2 | These data provide further evidence that CDK9 phosphorylates H1.4-S187, and that the level of pS187-H1.4 at genes is directly related to the extent of co-enrichment of CDK9.|that enrichment of pS187-H1.4 at genes is positively related to their transcription. | SIGNOR-279691 |
O14965 | Q96R06 | 1 | phosphorylation | up-regulates activity | 0.511 | We report here that Astrin acts as a mitotic phosphoprotein, and Aurora-A phosphorylates Astrin at Ser(115). The phosphorylation-deficient mutant Astrin S115A abnormally activates spindle assembly checkpoint and delays mitosis progression, decreases spindle stability, and induces chromosome misalignment. Mechanistic analyses reveal that Astrin phosphorylation mimicking mutant S115D, instead of S115A, binds and induces ubiquitination and degradation of securin, which sequentially activates Separase, an enzyme required for the separation of sister chromatids. | SIGNOR-276648 |
Q07955 | Q9HAZ1 | 0 | phosphorylation | up-regulates activity | 0.357 | In vitro, Clk/Sty efficiently phosphorylated the SR family member ASF/SF2 on serine residues located within its serine/arginine-rich region (the RS domain). Overexpression of the active Clk/Sty kinase caused a redistribution of SR proteins within the nucleus. These results suggest that Clk/Sty kinase directly regulates the activity and compartmentalization of SR splicing factors. | SIGNOR-273860 |
Q8N695 | P08047 | 0 | transcriptional regulation | up-regulates quantity by expression | 0.2 | Luciferase reporter assays of deletion mutants of SLC5A8 promoter demonstrated that a 295-bp region is essential for the basal promoter activity of the SLC5A8 gene. Further analysis indicated that the CCAAT boxes and GC boxes were involved in positive regulation of SLC5A8 promoter. Overexpression of two transcription factors, CCAAT/enhancer binding protein beta (C/EBPbeta) and specific transcription factor 1 (Sp1), upregulated the activities of the human SLC5A8 promoter and protein expression, suggesting that both C/EBPbeta and Sp1 transcription factors might have functions in SLC5A8 transcription. | SIGNOR-254059 |
P06493 | Q8NFH8 | 1 | phosphorylation | down-regulates activity | 0.34 | Phosphorylation of POB1 and Epsin by p34cdc2 kinase. Their phosphorylation sites (Ser411 of POB1 and Ser357 of Epsin) were determined. Phosphorylated Epsin and EpsinS357D formed a complex with α-adaptin less efficiently than wild type Epsin. | SIGNOR-262724 |
P23467 | P10912 | 1 | dephosphorylation | down-regulates | 0.295 | Inally, mrna tissue distribution of these ptps by rt-pcr analysis and coexpression of the wild-type ptps to test their ability to dephosphorylate ligand-activated ghr suggest ptp-h1 and ptp1b as potential candidates involved in ghr signaling. | SIGNOR-104580 |
Q5TA31 | Q9C029 | 0 | ubiquitination | up-regulates quantity by stabilization | 0.269 | Taken together, these data suggest that Trim7 directly ubiquitinates RACO-1. | SIGNOR-278536 |
P31269 | O00255 | 0 | methylation | up-regulates quantity by expression | 0.477 | Men1 excision causes reduction of Hoxa9 expression, colony formation by hematopoietic progenitors, and the peripheral white blood cell count. Menin directly activates Hoxa9 expression, at least in part, by binding to the Hoxa9 locus, facilitating methylation of H3K4, and recruiting the methylated H3K4 binding protein chd1 to the locus. | SIGNOR-255894 |
P51812 | Q99683 | 1 | phosphorylation | down-regulates activity | 0.2 | We provide evidence to show that RSK2 inhibits ASK1 by phosphorylating S83, T1109, and T1326 through a novel mechanism in which phospho-T1109/T1326 inhibits ATP binding to ASK1, while phospho-S83 attenuates ASK1 substrate MKK6 binding. | SIGNOR-276463 |
P08047 | P28906 | 1 | transcriptional regulation | up-regulates quantity by expression | 0.263 | Activation of the CD34 promoter by Sp1 requires the presence of a binding domain at -48 bp as well as the 5' untranslated region, which also binds Sp1 | SIGNOR-241481 |
P30291 | P53350 | 0 | phosphorylation | down-regulates quantity by destabilization | 0.642 | In the present study, we show that phosphorylation of S123 (pS123) by CDK promoted the binding of Wee1A to beta-TrCP through three independent mechanisms. S123 phosphorylation creates a PBD-binding motif and accelerates S53 phosphorylation by Plk1. | SIGNOR-276040 |
P78527 | P50876 | 0 | polyubiquitination | down-regulates quantity by destabilization | 0.568 | We show that RNF144A induces ubiquitination of DNA-PKcs in vitro and in vivo and promotes its degradation. | SIGNOR-272213 |
P27707 | P67775 | 0 | dephosphorylation | down-regulates activity | 0.2 | Protein phosphatase 2A regulates deoxycytidine kinase activity via Ser-74 dephosphorylation|Deoxycytidine kinase (dCK) is a critical enzyme for activation of anticancer nucleoside analogs. Its activity is controlled via Ser-74 phosphorylation. Here, we investigated which Ser/Thr phosphatase dephosphorylates Ser-74. In cells, the PP1/PP2A inhibitor okadaic acid increased both dCK activity and Ser-74 phosphorylation | SIGNOR-275803 |
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