IdA stringlengths 6 21 | IdB stringlengths 6 21 | labels float64 0 2 | mechanism stringclasses 40 values | effect stringclasses 10 values | score float64 0.1 0.99 ⌀ | sentence stringlengths 10 1.63k ⌀ | signor_id stringlengths 12 14 |
|---|---|---|---|---|---|---|---|
Q5VZV1 | P55072 | 1 | methylation | up-regulates activity | 0.308 | We reveal that METTL21C trimethylates p97 on the Lys315 residue and found that loss of this modification reduced p97 hexamer formation and ATPase activity in vivo. | SIGNOR-255918 |
Q13557 | Q14571 | 1 | phosphorylation | down-regulates activity | 0.308 | Phopho-specific antibodies demonstrate that InsP(3)R2 Ser-150 is phosphorylated in vivo by CaMKIIδ. The results of this study show that serine 150 of the InsP(3)R2 is phosphorylated by CaMKII and results in a decrease in the channel open probability. | SIGNOR-262692 |
P16220 | P98177 | 1 | binding | down-regulates activity | 0.308 | We provide evidence that the acetyltransferase creb-binding protein (cbp) binds foxo resulting in acetylation of foxo. This acetylation inhibits foxo transcriptional activity | SIGNOR-124711 |
Q9UGL1 | Q9H9S0 | 1 | transcriptional regulation | down-regulates quantity by repression | 0.308 | Phosphorylation of KDM5B at Ser1456 attenuated the occupancy of KDM5B on the promoters of pluripotency genes. | SIGNOR-273451 |
P45983 | Q15672 | 1 | phosphorylation | up-regulates | 0.308 | Phosphorylation of serine 68 of twist1 by mapks stabilizes twist1 protein and promotes breast cancer cell invasiveness. | SIGNOR-173417 |
P45983 | O43561 | 1 | phosphorylation | down-regulates | 0.308 | Lat, an adapter protein essential for t-cell signaling, is phosphorylated at its thr 155 by erk in response to t-cell receptor stimulation. Thr 155 phosphorylation reduces the ability of lat to recruit plcgamma1 and slp76, leading to attenuation of subsequent downstream events such as [ca2+]i mobilization and activation of the erk pathway.Mutational analysis revealed that t155 but not t94 or t140 is the site of jnk-mediated phosphorylation (figure 2b). Erk also phosphorylated lat at t155 (figure 2c), whereas p38, which was able to phosphorylate atf2, failed to induce threonine phosphorylation of lat (figure 2d). These results indicate that lat is directly phosphorylated by erk and jnk at the same site, t155. | SIGNOR-125774 |
P40424 | P42771 | 1 | transcriptional regulation | up-regulates quantity by expression | 0.308 | We show that the Pbx1 and Meis2 homeodomain proteins interact with Klf4 and can be recruited to DNA elements comprising a Klf4 site or G C box, with adjacent Meis and Pbx sites. Meis2d and Pbx1a activate expression of p15(Ink4a) and E-cadherin, dependent on the Meis2d transcriptional activation domain. We suggest a model in which genes with Klf4 sites can be cooperatively activated by Meis2/Pbx1 and Klf4, dependent primarily on recruitment by Klf4. | SIGNOR-267239 |
Q9BVN2 | Q9Y6K9 | 1 | null | up-regulates quantity by stabilization | 0.308 | NESCA interacts with the IKK complex by the N-terminal region of NEMO. This experiment revealed that the overexpression of NESCA completely abolished the TRAF6-mediated polyubiquitination of NEMO, as it appears by using either anti-HA (Fig. 5A) or anti-NEMO (Fig. 5B) antibodies on immunoprecipitated extracts. | SIGNOR-272775 |
P05412 | P98066 | 1 | transcriptional regulation | up-regulates quantity by expression | 0.308 | Tumor necrosis factor (TNF)-stimulated gene 6 (TSG-6) encodes a protein expressed during inflammation. We have previously shown that transcription factors of the NF-IL6 and AP-1 families cooperatively modulate activation of the TSG-6 gene by TNF or interleukin 1 (IL-1) through a promoter region that contains an NF-IL6 site (-106 to -114) and an AP-1 element | SIGNOR-254052 |
Q09472 | Q6DJT9 | 1 | acetylation | up-regulates | 0.308 | Plag1 and plagl2 are also regulated by acetylation. They are acetylated and activated by p300 and deacetylated and repressed by hdac7. | SIGNOR-140915 |
O96013 | P62826 | 1 | phosphorylation | up-regulates | 0.308 | We show that ran is a substrate for p21-activated kinase 4 (pak4) and that its phosphorylation on serine-135 increases during mitosis.Altogether, our findings strongly suggest that pak4-mediated phosphorylation of gdp- or gtp-bound ran modulates the assembly of complexes that are required at specific subcellular localizations for ran to carry out its functions during mitotic progression. | SIGNOR-167667 |
Q96JM2 | P40424 | 1 | binding | down-regulates activity | 0.308 | We demonstrated that ZFPIP is expressed in embryonic female genital tract but also in other PBX1 expression domains such as the developing head and the limb buds. We further showed that ZFPIP is able to bind physically and in vivo to PBX1 and moreover, that it prevents the binding of HOXA9/PBX complexes to their consensus DNA site. We suggest that ZFPIP is a new type of PBX1 partner that could participate in PBX1 function during several developmental pathways. | SIGNOR-264477 |
O14842 | P63096 | 1 | binding | up-regulates activity | 0.307 | 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-257071 |
Q96EP1 | Q96GM5 | 1 | polyubiquitination | down-regulates quantity by destabilization | 0.307 | Here we report that CHFR interacts with BRG1, SNF5, and BAF60a of the SWI/SNF-like BAF complex and ubiquitinates them to target for degradation through a proteasome-mediated pathway, and that SRG3/mBAF155 stabilizes these components by blocking their interaction with CHFR. These results suggest that CHFR enhances the degradation of the components of the SWI/SNF-like BAF complex by inducing their poly-ubiquitination. | SIGNOR-271459 |
P17252 | Q9UJY1 | 1 | phosphorylation | up-regulates activity | 0.307 | Hsp22 is phosphorylated by protein kinase c (at residues ser(14) and thr(63)) and by p44 mitogen-activated protein kinase (at residues ser(27) and thr(87)). Concerning the possible function of hsp22, no definitive conclusions can be drawn with the available data, although its function might be to bind to and modulate the activity of hsp27.Some Studies claimed that phosphorylation is required for the translocation | SIGNOR-107688 |
Q05655 | Q16820 | 1 | phosphorylation | down-regulates quantity | 0.307 | These findings suggest that activation of a protein kinase, presumably PKC, mediates PMA-induced hmeprinβ shedding. By labeling COS-1 cells transfected with mutant constructs lacking the potential phosphorylation sites, we identified Ser687 as the main 32P-acceptor. These data provide evidence that the cytoplasmic domain of hmeprinβ can function as a PKC substrate. | SIGNOR-263171 |
P19784 | Q92915 | 1 | phosphorylation | up-regulates activity | 0.307 | Bioluminescence-based screening of small molecule modulators of the FGF14:Nav1.6 complex identified 4,5,6,7 -: tetrabromobenzotriazole (TBB), a potent casein kinase 2 (CK2) inhibitor, as a strong suppressor of FGF14:Nav1.6 interaction. Inhibition of CK2 through TBB reduces the interaction of FGF14 with Nav1.6 and Nav1.2 channels. Mass spectrometry confirmed direct phosphorylation of FGF14 by CK2 at S228 and S230, and mutation to alanine at these sites modified FGF14 modulation of Nav1.6-mediated currents. | SIGNOR-275741 |
P06493 | O00399 | 1 | phosphorylation | up-regulates activity | 0.307 | Here, we show that the p27/p25 heterodimer undergoes mitotic phosphorylation by cyclin‐dependent kinase 1 (Cdk1) at a single site, p27 Thr186, to generate an anchoring site for polo‐like kinase 1 (Plk1) at kinetochores. | SIGNOR-264777 |
P19784 | Q01892 | 1 | phosphorylation | down-regulates quantity by destabilization | 0.307 | Phosphorylation of the Spi-B transcription factor reduces its intrinsic stability. | Serine residues 37 in the transactivation domain and 129, 144 and 146 in the PEST domain of Spi-B are phosphorylated by CKII in vitro | The CKII phosphorylation sites mapped in vitro are phosphorylated in vivo | SIGNOR-251042 |
Q07912 | O00401 | 1 | phosphorylation | up-regulates activity | 0.307 | Because TNK2 phosphorylation of WASL increases its actin nucleation activity ( xref ), we reasoned that it might be possible to complement the TNK2 deficiency by overexpression of WASL.|For NCK1, based on its reported binding to WASL and TNK2, we hypothesized that its function is to recruit WASL to TNK2, which could then activate WASL via phosphorylation ( xref ; xref ). | SIGNOR-280155 |
P26583 | Q03052 | 1 | binding | up-regulates activity | 0.307 | HMG2 and Oct2 interact via their HMG domains and POU homeodomains, respectively. This interaction is not restricted to Oct2, as other members of the octamer transcription factor family like Oct1 and Oct6 also interact with HMG2. The interaction with HMG2 results in a marked increase in the sequence-specific DNA binding activity of the Oct proteins | SIGNOR-240148 |
P68400 | P41236 | 1 | phosphorylation | up-regulates activity | 0.307 | Recombinant wild-type I-2 and the Ala-120/121 mutant were phosphorylated synergistically by GSK-3 and casein kinase II. The Thr-72 and Ser-86 mutants, however, did not undergo this synergistic phosphorylation. Our studies indicate that Thr-72 is the only GSK-3 site and that Ser-86 is the casein kinase II site required for the potentiation of GSK-3 action. | SIGNOR-250929 |
P49674 | Q13114 | 1 | phosphorylation | up-regulates activity | 0.307 | CK1ɛ interacted with and phosphorylated TRAF3 at Ser349, which thereby promoted the Lys63 (K63)-linked ubiquitination of TRAF3 and subsequent recruitment of the kinase TBK1 to TRAF3. | SIGNOR-277212 |
Q15139 | Q92934 | 1 | phosphorylation | down-regulates | 0.307 | Pkcs phosphorylate bad under in vitro conditions, and the association of phosphorylated bad with pkc-mu or pkc-epsilon, as shown by immunoprecipitation, indicated direct involvement of pkcs in bad phosphorylation. To confirm these results, cells overexpressing pegfp-n1, wt-bad, or bad with a single site mutated (ser112ala;ser136ala;ser155ala), two sites mutated (ser(112/136)ala;ser(112/155)ala;ser(136/155)ala), or the triple mutant were tested. Igf-i protected completely against rapamycin-induced apoptosis in cells overexpressing wt-bad and mutants having either one or two sites of phosphorylation mutated | SIGNOR-163920 |
Q13177 | P08670 | 1 | phosphorylation | down-regulates activity | 0.307 | In vitro analyses revealed that vimentin served as an excellent substrate for PAK. This phosphorylated vimentin lost the potential to form 10 nm filaments. We identified Ser25, Ser38, Ser50, Ser65 and Ser72 in the amino-terminal head domain as the major phosphorylation sites on vimentin for PAK. | SIGNOR-250243 |
P68400 | P13349 | 1 | phosphorylation | up-regulates activity | 0.307 | Here, we report that Myf-5 protein constitutes a substrate for phosphorylation in vitro by protein kinase CK2. We identified two potential phosphorylation sites at serine49 and serine133, both of which seem to be necessary for Myf-5 activity. | SIGNOR-250922 |
P49137 | Q14134 | 1 | phosphorylation | up-regulates activity | 0.307 | ATDC was phosphorylated directly by MAPKAP kinase 2 (MK2) at Ser550 in an ATM-dependent manner. Phosphorylation at Ser-550 by MK2 was required for the radioprotective function of ATDC. | SIGNOR-273675 |
P49841 | Q9NZQ7 | 1 | phosphorylation | down-regulates quantity by destabilization | 0.307 | We show that glycogen synthase kinase 3β (GSK3β) interacts with PD-L1 and induces phosphorylation-dependent proteasome degradation of PD-L1 by β-TrCP. | SIGNOR-277275 |
P17612 | P25054 | 1 | phosphorylation | down-regulates activity | 0.307 | Changing a serine residue (Ser(2054)) to aspartic acid mutated the potential protein kinase A site adjacent to NLS2(APC), resulting in both inhibition of the NLS2(APC)-mediated nuclear import of a chimeric beta-galactosidase fusion protein and a reduction of full-length APC nuclear localization. | SIGNOR-250335 |
Q9H093 | O95835 | 1 | phosphorylation | down-regulates | 0.307 | Phosphorylation at ser-464 by nuak1 and nuak2 leads to decreased protein level and is required to regulate cellular senescence and cellular ploidy | SIGNOR-161796 |
Q13283 | P19525 | 1 | binding | up-regulates activity | 0.307 | We show that G3BP1 can activate effectors of the innate immune transcriptional program, culminating in enhanced expression of a set of cytokines. We demonstrate that a subset of PKR is recruited to SGs, that close-proximity interactions between G3BP1 and PKR complexes increase in response to stress and PKR activation, that once activated PKR no longer associates with SGs, and that the PXXP domain of G3BP1 is essential for PKR recruitment to SGs and PKR activation in cells. Together, these findings suggest that G3BP1 plays an important role in the recruitment of PKR to SGs and suggest that activation of PKR can take place at the SG. | SIGNOR-260750 |
P22694 | Q92917 | 1 | phosphorylation | up-regulates activity | 0.307 | Using yeast two-hybrid screening with the PKA Cβ2 subunit as bait we identified GPKOW, also known as MOS2 homolog or T54 protein, as an interaction partner for Cβ2.PKA phosphorylates GPKOW at S27 and T316 in vitro. GPKOWs ability to bind RNA is sensitive to mutations of its PKA phosphorylation sites. | SIGNOR-266298 |
P17252 | O60479 | 1 | phosphorylation | down-regulates activity | 0.307 | Dlx3 is primarily phosphorylated by PKC alpha. By deletion and mutational analysis, we show that the serine residue S(138), located in the homeodomain of Dlx3 protein, was specifically phosphorylated by PKC. The phosphorylation of purified Dlx3 proteins by PKC partially inhibited formation of complexes between Dlx3 protein and DNA. These results suggest that Dlx3 protein can be directly phosphorylated by PKC and this affects the DNA binding activity of Dlx3. | SIGNOR-249096 |
P17612 | Q14978 | 1 | phosphorylation | up-regulates | 0.307 | Here we demonstrate that protein kinase a (pka)-dependent phosphorylation of nopp140 at ser 627, together with c/ebpbeta, induces agp gene expression synergistically. | SIGNOR-91186 |
Q9UBX2 | P78337 | 1 | transcriptional regulation | up-regulates quantity by expression | 0.307 | DUX4, a candidate gene of facioscapulohumeral muscular dystrophy, encodes a transcriptional activator of PITX1 | SIGNOR-261590 |
P35680 | P18846 | 1 | binding | up-regulates activity | 0.307 | The mammalian two-hybrid system showed that the region aa 393 to 476 of LFB3 is involved in the interaction with CREB or ATF1. The importance of this region for mediating cAMP induction was confirmed in transient transfection assays. | SIGNOR-241320 |
Q8N5S9 | Q8TDC3 | 1 | phosphorylation | up-regulates activity | 0.307 | In transfected COS-7 cells, kinase activity and Thr (189) phosphorylation of overexpressed SAD-B were significantly enhanced by coexpression of constitutively active CaMKKalpha (residues 1-434) in a manner similar to that observed with coexpression of LKB1, STRAD, and MO25.|Taken together, these results indicate that CaMKKalpha is capable of activating SAD-B through phosphorylation of Thr (189) both in vitro and in vivo and demonstrate for the first time that CaMKK may be an alternative activating kinase for SAD-B. | SIGNOR-280202 |
P17612 | P36382 | 1 | phosphorylation | up-regulates activity | 0.307 | Gap junction channels formed of Cx40 are modulated by protein-kinase-A-mediated phosphorylation. Macroscopic conductance and permeability of Cx40 gap junctions is strongly increased by cAMP. two serine residues that can be phosphorylated by PKA, S120 and S345 | SIGNOR-249982 |
Q96RG2 | P61964 | 1 | phosphorylation | up-regulates activity | 0.307 | Pask directly interacts with and phosphorylates Wdr5 at Ser49.|We therefore believe that differentiation cues act, at least in part, to drive the myogenic transcriptional program via Pask activation and phosphorylation of Wdr5. | SIGNOR-278266 |
P68400 | P12259 | 1 | phosphorylation | down-regulates activity | 0.307 | Factor Va, the essential cofactor for prothrombinase, is phosphorylated on the acidic COOH terminus of the heavy chain of the cofactor, at Ser692, by a platelet membrane-associated casein kinase II (CKII). | The phosphorylated cofactor has increased susceptibility to inactivation by activated protein C, since phosphorylated factor Va was found to be inactivated approximately 3-fold faster than its native counterpart. | SIGNOR-250862 |
P26583 | P14859 | 1 | binding | up-regulates activity | 0.307 | HMG2 and Oct2 interact via their HMG domains and POU homeodomains, respectively. This interaction is not restricted to Oct2, as other members of the octamer transcription factor family like Oct1 and Oct6 also interact with HMG2. The interaction with HMG2 results in a marked increase in the sequence-specific DNA binding activity of the Oct proteins | SIGNOR-240151 |
P23470 | P12931 | 1 | dephosphorylation | down-regulates activity | 0.307 | PTPRG activation by the P1-WD peptide affected the tyrosine phosphorylation of several signaling molecules. Data analysis identified 31 molecules whose phosphorylation was modified in a statistically significant manner (Table I). inhibition of ABL1, BMX, BTK, DAB1, ITGB1, JAK2, KDR, KIT, LIMK1, MET, PDGFRB, SHC1, and VCL correlates with tyrosine dephosphorylation. In contrast, SRC inhibition correlates with hyperphosphorylation of the inhibitory Tyr530 residue and with dephosphorylation of the activatory Tyr419. Moreover, CDK2 and CTTN inhibition correlates with a hyperphosphorylation of the inhibitory Tyr15 and Tyr470, respectively. In contrast, a subgroup of 13 proteins, including BLNK, DOK2, ERBB2, GRIN2B, INSR, PDGFRA, PRKCD, PXN, STAT1, STAT2, STAT3, STAT5A, and ZAP70, appears to be activated by PTPRG activity. | SIGNOR-254725 |
Q9UJT9 | O15392 | 1 | binding | down-regulates quantity by destabilization | 0.307 | Fbxl7 targets survivin for polyubiquitylation and proteasomal degradation.these data suggest that the Skp1·Cul1·F-box protein complex subunit Fbxl7 modulates mitochondrial function by controlling the cellular abundance of survivin. These results suggest that both Lys-90 and Lys-91 are critical for Fbxl7-mediated polyubiquitylation. | SIGNOR-272436 |
P17612 | P27708 | 1 | phosphorylation | down-regulates | 0.307 | Protein kinase a phosphorylation at thr456 of the multifunctional protein cad antagonizes activation by the map kinase cascade. | SIGNOR-151816 |
P68400 | P49810 | 1 | phosphorylation | up-regulates activity | 0.307 | In vitro the large hydrophilic loop of PS-2 between transmembrane domains 6 and 7 can be phosphorylated by casein kinase-1 (CK-1) and CK-2, but not by PKA or PKC. Quantitative analysis of in vitro phosphorylation demonstrates the presence of two phosphorylation sites for CK-1 and a single site for CK-2. A deletion analysis revealed that the CTF of PS-2 is phosphorylated in vivo within an acidic sequence containing three potential phosphorylation sites for CKs (serines 327, 330, and 335). These data suggest that CK type protein kinases phosphorylate the CTF of PS-2 within its hydrophilic loop domain in vivo. Interestingly, the potential phosphorylation sites are located directly adjacent to the recently identified caspase cleavage sites. | SIGNOR-250934 |
Q8WVD3 | Q9UJU2 | 1 | polyubiquitination | down-regulates quantity by destabilization | 0.307 | Here, we show that NARF induces the ubiquitylation of TCF/LEF in vitro and in vivo, and functions as an E3 ubiquitin-ligase that specifically cooperates with the E2 conjugating enzyme E2-25K. We found that NLK augmented NARF binding and ubiquitylation of TCF/LEF, and this required NLK kinase activity. The ubiquitylated TCF/LEF was subsequently degraded by the proteasome. | SIGNOR-271595 |
P17612 | Q92917 | 1 | phosphorylation | up-regulates activity | 0.307 | PKA phosphorylates GPKOW at S27 and T316 in vitro. GPKOWs ability to bind RNA is sensitive to mutations of its PKA phosphorylation sites. | SIGNOR-266309 |
P17612 | P52888 | 1 | phosphorylation | up-regulates activity | 0.307 | PKA phosphorylation is suggested to play a regulatory role in EP24.15 enzyme activity. Mutation analysis of each putative PKA site, in vitro phosphorylation, and phosphopeptide mapping indicated serine 644 as the phosphorylation site. The most dramatic change upon PKA phosphorylation was a substrate-specific, 7-fold increase in both K(m) and k(cat) for GnRH. | SIGNOR-250060 |
P17252 | P15382 | 1 | phosphorylation | down-regulates activity | 0.307 | Inhibition of the current was not seen in channels in which Ser103 was replaced by Ala, although other properties of the current were unchanged. These results indicate that inhibition of the potassium current results from direct phosphorylation of the channel subunit protein at Ser103. | SIGNOR-248852 |
Q16539 | Q9H3D4 | 1 | phosphorylation | down-regulates quantity by destabilization | 0.307 | P38α phosphorylates and destabilizes p63. | SIGNOR-277414 |
P60484 | P35813 | 1 | binding | up-regulates | 0.307 | Upon complex formation with pten, ppm1a is protected from degradation induced by the tgf-? Signaling. this study establishes a novel role for nuclear pten in the stabilization of ppm1a. | SIGNOR-178643 |
Q13535 | Q86YC2 | 1 | phosphorylation | up-regulates activity | 0.307 | ATR promotes PALB2 accumulation at DNA damage sites.|In the context of PALB2 regulation, the phosphorylation of PALB2 by ATR plays a positive role in PALB2 recruitment. | SIGNOR-279588 |
Q9Y458 | P56178 | 1 | transcriptional regulation | down-regulates quantity by repression | 0.307 | the main function of TBX22 as shown in misexpression experiments is to decrease proliferation. We subsequently uncovered three targets of TBX22, DLX5, MSX2, and TBX22 itself. All are downregulated in the presence of viral-derived hTBX22. | SIGNOR-265566 |
Q05655 | P48048 | 1 | null | up-regulates activity | 0.307 | To determine whether this channel is a substrate for PKA, ROMK tagged with the hemagglutinin epitope was transiently transfected into HEK293 cells. In vitro labeling of immunoprecipitated proteins from transfected cells showed that ROMK could be phosphorylated by PKA. | Taken together, these results provide strong evidence that direct phosphorylation of the channel polypeptide by PKA is involved in channel regulation and PKA-dependent phosphorylation is essential for ROMK channel activity. | SIGNOR-248943 |
P53004 | P05771 | 1 | phosphorylation | up-regulates | 0.307 | Human biliverdin reductase, a previously unknown activator of protein kinase c ?II the phosphorylation of thr500 was confirmed by immunoblotting of hbvr.pkc betaii immunocomplex. | SIGNOR-152181 |
Q9UQM7 | Q9NQC7 | 1 | phosphorylation | up-regulates activity | 0.307 | NMDA treatment of cultured hippocampal neurons causes recruitment of CYLD, as well as CaMKII, to the postsynaptic density (PSD), as shown by immunoelectron microscopy, […] Purified CaMKII phosphorylates CYLD on at least three residues (S-362, S-418, and S-772 on the human CYLD protein Q9NQC7-1) and promotes its deubiquitinase activity. | SIGNOR-266442 |
Q8TF68 | P03956 | 1 | transcriptional regulation | up-regulates quantity by expression | 0.307 | Luciferase activity driven by the MMP-1 promoter also increased by 2.5- to 3-fold. In contrast, CIZ had no effect on the luciferase activity from the MMP-1 promoter that was mutated at the CIZ binding consensus sequence. These results show that the CIZ transactivates the MMP-1 promoter through this sequence. | SIGNOR-266229 |
Q9Y4K3 | Q53ET0 | 1 | ubiquitination | down-regulates quantity | 0.307 | Consistently, TRAF6 reduced G6pase gene expression or reporter activity induced by wild-type CRTC1 and CRTC2 but not TRAF6-interaction-defective CRTC1 and CRTC2 (XREF_FIG and XREF_SUPPLEMENTARY).|Indeed, TRAF6, the E3 ubiquitin ligase activated by IL-1beta associates with and ubiquitinates CRTC2. | SIGNOR-278725 |
P17252 | Q06210 | 1 | phosphorylation | down-regulates activity | 0.307 | Phosphorylation of human glutamine:fructose-6-phosphate amidotransferase by cAMP-dependent protein kinase at serine 205 blocks the enzyme activity. | SIGNOR-249040 |
P17252 | P05114 | 1 | phosphorylation | down-regulates | 0.307 | Protein kinases that phosphorylate hmg-14 17 at the major sites have been implicated from previous in vitro studies. Protein kinase c and a similar calcium phospholipid-dependent kinase have been reported to phosphorylate both proteins in vitro, where the phosphorylation of hmg-17 occurs predominantly at ser24 and to a lesser degree at ser28. Phosphorylation of hmg-14 at ser6 by camp- or cgmp-dependent kinases has also been reported. Thus, other kinases may contribute to phosphorylation at ser6 in response to oa. Ser88 and ser98 on hmg-14 are also phosphorylated by casein kinase ii in vitro. we conclude that the correlation we observe reflects a causal relationship, in which phosphorylation somehow facilitates the redistribution of hmg-14 and -17 toward non-nuclear pools. | SIGNOR-76286 |
P17612 | O95295 | 1 | phosphorylation | up-regulates activity | 0.307 | PKA-phosphorylation of Snapin significantly increases its binding to synaptosomal-associated protein-25 (SNAP-25). Mutation of Snapin serine 50 to aspartic acid (S50D) mimics this effect of PKA phosphorylation | SIGNOR-250053 |
P17612 | P05114 | 1 | phosphorylation | down-regulates activity | 0.307 | PKA preferentially phosphorylates serine 6 in human HMGN1. specific phosphorylation of the NBD of HMGN proteins serves to prevent the interaction of these proteins with their chromatin targets during mitosis. | SIGNOR-249993 |
P68400 | P00736 | 1 | phosphorylation | down-regulates activity | 0.307 | We provide evidence that this kinase phosphorylates Clr at the level of Ser189. | Accessibility of Ser189 was low in intact C1r, due in part to the presence of one of the oligosaccharides borne by the alpha region, further reduced in the presence of calcium, and abolished when C1r was incorporated into the C1s-C1r-C1r-C1s tetramer or the C1 complex. | SIGNOR-250833 |
P63096 | O14939 | 1 | binding | down-regulates | 0.307 | The results of this study suggest that membrane phospholipase d activity can be negatively regulated via gi | SIGNOR-48256 |
P19784 | P13349 | 1 | phosphorylation | up-regulates activity | 0.307 | Here, we report that Myf-5 protein constitutes a substrate for phosphorylation in vitro by protein kinase CK2. We identified two potential phosphorylation sites at serine49 and serine133, both of which seem to be necessary for Myf-5 activity. | SIGNOR-251016 |
P19784 | P41236 | 1 | phosphorylation | up-regulates activity | 0.307 | Recombinant wild-type I-2 and the Ala-120/121 mutant were phosphorylated synergistically by GSK-3 and casein kinase II. The Thr-72 and Ser-86 mutants, however, did not undergo this synergistic phosphorylation. Our studies indicate that Thr-72 is the only GSK-3 site and that Ser-86 is the casein kinase II site required for the potentiation of GSK-3 action. | SIGNOR-251021 |
P17612 | Q12809 | 1 | phosphorylation | up-regulates | 0.307 | Deletion of protein kinase a phosphorylation sites in the herg potassium channel inhibits activation shift by protein kinase afour consensus pka phosphorylation sites (s283a, s890a, t895a, s1137a) | SIGNOR-70726 |
O15550 | P31273 | 1 | transcriptional regulation | up-regulates quantity by expression | 0.307 | 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-260029 |
Q8IYU2 | P24385 | 1 | ubiquitination | down-regulates quantity by destabilization | 0.307 | Mechanistically, the tumor-suppressor function of HACE1 is dependent on its E3 ligase activity and HACE1 controls adhesion-dependent growth and cell cycle progression during cell stress through degradation of cyclin D1. | SIGNOR-271405 |
P17612 | P60983 | 1 | phosphorylation | up-regulates activity | 0.307 | Protein kinase A (PKA)-phosphorylated GMF is a potent inhibitor of extracellular signal-regulated kinase (ERK) and enhancer of p38; both are subfamilies of mitogen-activated protein (MAP) kinase, suggesting GMF as a bifunctional regulator of the MAP kinase cascades. PKA is capable of phosphorylating threonine 26 and serine 82. | SIGNOR-249983 |
Q9NRD5 | Q01954 | 1 | relocalization | up-regulates activity | 0.307 | we found that the PDZ domain-containing protein PICK1 (protein interacting with C kinase) interacts specifically with the C-termini of BNC1 and ASIC. Our studies showing association of recombinant PICK1 with ASIC and BNC1, and the presence of both PICK1 and ASIC in the synaptosomal fraction | SIGNOR-223414 |
Q06330 | P38936 | 1 | transcriptional regulation | up-regulates quantity by expression | 0.307 | Induction of the p21WAF1/Cip1 gene by Notch 1 activation in differentiating keratinocytes is associated with direct targeting of the RBP-J_ protein to the p21 promoter. | SIGNOR-252032 |
Q99558 | P19634 | 1 | phosphorylation | up-regulates activity | 0.307 | The Nck-interacting kinase (NIK) phosphorylates the Na+-H+ exchanger NHE1 and regulates NHE1 activation by platelet-derived growth factor.|We now show that NIK binds to and divergently activates the plasma membrane Na(+)-H(+) exchanger NHE1. | SIGNOR-279632 |
P12004 | O95944 | 1 | binding | down-regulates activity | 0.307 | NK cells play an important role in the early immune response to cancer. The NKp44 activating receptor is the only natural cytotoxicity receptor that is expressed exclusively by primate NK cells, yet its cellular ligands remain largely unknown. | SIGNOR-260043 |
Q9UII4 | P22392 | 1 | ubiquitination | up-regulates quantity by stabilization | 0.307 | HERC5 is required for ubiquitination of Nm23B. In summary, Nm23B ubiquitination is mediated by HERC5. Stable Nm23B protein in presence of HERC5 as well as proteasome-independent ubiquitination suggest that ubiquitination of Nm23B serves a different purpose than marking it for degradation. | SIGNOR-271778 |
P05771 | Q99418 | 1 | phosphorylation | down-regulates activity | 0.307 | ARNO is phosphorylated in vivo by PKC on a single serine residue, S392, located within the carboxy-terminal polybasic domain. Mutation of S392 to alanine does not prevent ARNO-mediated actin rearrangements, suggesting that phosphorylation does not lead to ARNO activation [6]. Here, we report that phosphorylation negatively regulates ARNO exchange activity through a 'PH domain electrostatic switch'. | SIGNOR-249024 |
P17096 | Q03052 | 1 | binding | up-regulates activity | 0.307 | Direct contacts were identified between the POU domain of Tst-1/Oct-6 and a short stretch of 10 amino acids in the central portion of HMG-I/Y. In the presence of HMG-I/Y, Tst-1/Oct-6 exhibited an increased affinity for this AT-rich element. | SIGNOR-240155 |
O15552 | P09471 | 1 | binding | up-regulates activity | 0.307 | 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-257075 |
Q05655 | O15350 | 1 | phosphorylation | up-regulates | 0.307 | The results show that pkcdeltacf phosphorylates the p73beta transactivation and dna-binding domains. pkcdeltacf-mediated phosphorylation of p73beta is associated with accumulation of p73beta and induction of p73beta-mediated transactivation. | SIGNOR-90279 |
P17252 | Q99418 | 1 | phosphorylation | down-regulates activity | 0.307 | ARNO is phosphorylated in vivo by PKC on a single serine residue, S392, located within the carboxy-terminal polybasic domain. Mutation of S392 to alanine does not prevent ARNO-mediated actin rearrangements, suggesting that phosphorylation does not lead to ARNO activation [6]. Here, we report that phosphorylation negatively regulates ARNO exchange activity through a 'PH domain electrostatic switch'. | SIGNOR-249023 |
Q92794 | Q13950 | 1 | binding | up-regulates | 0.307 | Moz and morf both interact with runx2 / while morf does not acetylate runx2, its sm domain potentiates runx2-dependent transcriptional activation. | SIGNOR-117332 |
Q13555 | P28329 | 1 | phosphorylation | up-regulates activity | 0.307 | Using mass spectrometry, we identified threonine 456 as a new phosphorylation site in choline acetyltransferase from A beta-(1-42)-treated cells and in purified recombinant ChAT phosphorylated in vitro by calcium/calmodulin-dependent protein kinase II (CaM kinase II). | This phosphorylation combination was observed in choline acetyltransferase from A beta-(1-42)-treated cells. Treatment of cells with A beta-(1-42) resulted in two phases of activation of choline acetyltransferase, the first within 30 min and associated with phosphorylation by protein kinase C and the second by 10 h and associated with phosphorylation by both CaM kinase II and protein kinase C. | SIGNOR-250693 |
P78527 | P52945 | 1 | phosphorylation | down-regulates quantity by destabilization | 0.307 | The interaction of PDX-1 with Ku subunits and its phosphorylation on threonine 11 by the DNA-PK appear to be implicated in its degradation by the proteosome. | SIGNOR-225542 |
Q9H1B7 | P01210 | 1 | transcriptional regulation | down-regulates quantity by repression | 0.307 | EAP1 encoded a nuclear protein expressed in neurons involved in the inhibitory and facilitatory control of reproduction. EAP1 transactivated genes required for reproductive function, such as GNRH1, and repressed inhibitory genes, such as preproenkephalin. It contained a RING finger domain of the C3HC4 subclass required for this dual transcriptional activity.These results suggest that EAP1 is a transcriptional regulator that, acting within the neuroendocrine brain, contributes to controlling female reproductive function. | SIGNOR-267155 |
P05771 | P56537 | 1 | phosphorylation | down-regulates activity | 0.307 | Our results show that release of eIF6 from 60S subunits may operate, in mammalian cells, through a RACK1–PKC betaII pathway. |Loading 60S subunits with eIF6 caused a dose-dependent translational block and impairment of 80S formation, which were reversed by expression of RACK1 and stimulation of PKC in vivo and in vitro. PKC stimulation led to eIF6 phosphorylation, and mutation of a serine residue in the carboxy terminus of eIF6 impaired RACK1/PKC-mediated translational rescue. |S235A eIF6 inhibits ribosomal joining in the presence of RACK1–PKCbetaII | SIGNOR-249245 |
P67870 | Q86VB7 | 1 | phosphorylation | up-regulates activity | 0.307 | Interaction of CD163 with the regulatory subunit of casein kinase II (CKII) and dependence of CD163 signaling on CKII and protein kinase C. | Inhibition studies using specific kinase inhibitors reveal that both CKII and PKC are involved in the CD163 signaling mechanism resulting in the secretion of proinflammatory cytokines. | SIGNOR-251056 |
P13010 | P52945 | 1 | binding | down-regulates quantity by destabilization | 0.307 | The interaction of PDX-1 with Ku subunits and its phosphorylation on threonine 11 by the DNA-PK appear to be implicated in its degradation by the proteosome. | SIGNOR-225537 |
P54646 | P05549 | 1 | phosphorylation | up-regulates activity | 0.307 | Inhibition of AMPKalpha2 with either siRNA or compound C significantly suppressed the AngII- or nicotine enhanced AP-2alpha activity and the binding of AP-2alpha to DNA.|We report that nicotine, a major component of cigarette smoke, activates AMPK in VSMCs and that AMPKalpha2 phosphorylates AP-2alpha at serine 219 resulting in aberrant expression of MMP2 and consequent AAA formation. | SIGNOR-279648 |
P14174 | P00441 | 1 | relocalization | down-regulates quantity by destabilization | 0.307 | Here, we show that MIF inhibits mutant SOD1 nuclear clearance when overexpressed in motor neuron-like NSC-34 cells|SOD1WT is evenly distributed between the cytoplasm and the nucleus while mutant SOD1G93A shows predominantly cytoplasmic distribution (Fig. 1a, b). Expression of MIF in cells expressing SOD1WT had no effect on the distribution of the SOD1WT–EGFP protein. However, expression of MIF together with the mutant SOD1G93A–EGFP, inhibited the nuclear clearance of misfolded SOD1 resulting in a more wild-type-like distribution of the mutant SOD1 protein | SIGNOR-262797 |
P05129 | Q16625 | 1 | phosphorylation | up-regulates activity | 0.307 | Protein kinase C regulates the phosphorylation and cellular localization of occludin. Ser(338) of occludin was identified as an in vitro protein kinase C phosphorylation site using peptide mass fingerprint analysis and electrospray ionization tandem mass spectroscopy. Both the phosphorylation of occludin and its incorporation into tight junctions induced by calcium switch were markedly inhibited by the PKC inhibitor GF-109203X. | SIGNOR-249107 |
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 |
P12931 | Q9H2X6 | 1 | phosphorylation | up-regulates activity | 0.307 | Using mass spectrometry we identified 9 Src-mediated Tyr-phosphorylation sites within HIPK2, 5 of them positioned in the kinase domain.|We demonstrate that ectopic expression of Src increases the half-life of HIPK2 by interfering with Siah-1-mediated HIPK2 degradation. | SIGNOR-278989 |
Q9UQM7 | O14713 | 1 | phosphorylation | up-regulates activity | 0.307 | The point mutation T38D localized within the optimal CaMKII recognition motif of ICAP-1alpha results in a strong defect in cell spreading which cannot be overcome by the inhibition of the endogenous CaMKII. This fact strongly suggests that the phosphorylation of Threonine 38 by CaMKII modulates the alpha5beta1 integrin function. Conversely, the mutation T38A produces an analog of ICAP-1alpha that cannot be phosphorylated and that stimulates cell spreading on fibronectin to a similar extent when CaMKII is inhibited. | SIGNOR-250632 |
Q9Y4K3 | Q99538 | 1 | polyubiquitination | up-regulates quantity by stabilization | 0.307 | We demonstrate that TRAF6 ubiquitinates the proform of AEP through K63-linked polyubiquitin, reversible by USP17, and forms a complex with HSP90α to subsequently promote pro-AEP intracellular stability as well as secretion. We now present evidence that AEP is a substrate for TRAF6 ubiquitination, resulting in AEP/TRAF6/HSP90α complex formation. | SIGNOR-272853 |
P00533 | P61925 | 1 | phosphorylation | up-regulates | 0.307 | The difference in inhibitory potency between pki_ and pki_ has been attributed to the absence of a tyrosine residue (tyr7) in pki_ that is present in the nh2-terminal region of pki_. This suggests that the absence of a single amino acid residue can result in variations in how the catalytic subunit of camp-dependent protein kinase interacts with pki which ultimately can result in alterations in pki inhibitory potency. | SIGNOR-22455 |
P68400 | P05549 | 1 | phosphorylation | up-regulates | 0.307 | Ck2 phosphorylates ap-2_ and increases its transcriptional activity | SIGNOR-175130 |
P17612 | Q14847 | 1 | phosphorylation | down-regulates activity | 0.306 | Lasp-1 binds to non-muscle filamentous (F) actin in vitro in a phosphorylation-dependent manner. Phosphorylation of recombinant lasp-1 with recombinant PKA increased the Kd and decreased the Bmax for lasp-1 binding to F-actin. PKA-dependent phosphorylation sites in rabbit lasp-1 to S99 and S146 | SIGNOR-250074 |
Q00987 | Q13469 | 1 | ubiquitination | down-regulates quantity | 0.306 | MDM2 negatively regulates NFATc2 and T cell activation.|The E3 ubiquitin ligase MDM2 is known to induce NFATc2 ubiquitination in a breast cancer cell line 24. | SIGNOR-278657 |
P49842 | P01111 | 1 | phosphorylation | up-regulates activity | 0.306 | STK19 Phosphorylates NRAS Protein at Serine 89|STK19 phosphorylates NRAS to enhance its binding to its downstream effectors and promotes oncogenic NRAS-mediated melanocyte malignant transformation.| | SIGNOR-264566 |
Q13464 | Q99717 | 1 | phosphorylation | up-regulates activity | 0.306 | The results showed that SMAD5 was directly phosphorylated at Ser463/465 by ROCK1 (Fig.\u00a04g).|These data indicated that the activation of SMAD5 induced by TEM8 was mediated directly by the RhoC/ROCK1 pathway.To evaluate the effect of SMAD5 on the cellular functions of TEM8, SMAD5 was knockdown in TEM8-overexpressing cells. | SIGNOR-280107 |
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