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 |
|---|---|---|---|---|---|---|---|
P19838 | P04150 | 0 | transcriptional regulation | down-regulates quantity by repression | 0.6 | We have described how the receptor uses several means to achieve repression of the genes regulated by AP-1 and NF-KB proteins | SIGNOR-251680 |
P63027 | P08247 | 0 | binding | up-regulates quantity | 0.6 | Synaptophysin I interacts with VAMP2 and controls its subcellular distribution. On the SV membrane, VAMP2 is engaged in a complex with synaptophysin I, which is mutually exclusive with the formation of fusogenic SNARE complexes. This model implicates synaptophysin I in escorting VAMP2 to the sites where exocytosis must take place exclusively after the arrival of the appropriate stimulus. We show that, at early stages along the secretory pathway, synaptophysin I directs sorting of VAMP2 to vesicles exhibiting limited availability for constitutive exocytosis. | SIGNOR-264102 |
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 |
P55011 | Q9UEW8 | 0 | phosphorylation | up-regulates activity | 0.6 | This phosphorylation event activates PASK, which in turn phosphorylates and activates NKCC1 | SIGNOR-264642 |
P25490 | O15379 | 0 | deacetylation | down-regulates activity | 0.6 | Previous studies have established that YY1 interacts with histone acetyltransferases p300 and CREB-binding protein (CBP) and histone deacetylase 1 (HDAC1), HDAC2, and HDAC3. Here, we present evidence that the activity of YY1 is regulated through acetylation by p300 and PCAF and through deacetylation by HDACs. YY1 was acetylated in two regions: both p300 and PCAF acetylated the central glycine-lysine-rich domain of residues 170 to 200, and PCAF also acetylated YY1 at the C-terminal DNA-binding zinc finger domain. Acetylation of the central region was required for the full transcriptional repressor activity of YY1 and targeted YY1 for active deacetylation by HDACs. | SIGNOR-268837 |
P01112 | Q5VWQ8 | 0 | gtpase-activating protein | down-regulates activity | 0.6 | The GAP domain of DAB2IP is homologous to other Ras-GAPs, such as GAP120 and neurofibromin (NF1), and can stimulate the GTPase activity of RAS proteins both in vitro and in cancer cell lines. DAB2IP is able to stimulate in vitro and in vivo the GTPase activity of RAS proteins (H-Ras, K-Ras, and N-Ras) facilitating GTP hydrolysis to GDP. | SIGNOR-254745 |
Q14765 | Q16539 | 0 | phosphorylation | up-regulates | 0.599 | All stats are phosphorylated on at least one serine residue in their tad specifically, ser727 in stats 1 and 3 and ser721 in stat4. Stat serine kinases have been identified through the use of inhibitors, dominant-negative alleles, and in vitro kinase assays. They include mapk (p38mapk: stats 1, 3, 4;erk: stat3, 5;jnk: stat3), pkc_ (stat1, stat3), mtor (stat3), nlk (stat3 (42)), and camkii and ikk_ (stat1 (39, 40, 43)).STAT Serine phosphorylation regulates transcriptional activity (see below). | SIGNOR-154787 |
Q14344 | P25116 | 0 | binding | up-regulates | 0.599 | The protease-activated receptors (PAR)2 are a class of G protein-coupled receptors (GPCR) that are activated by the proteolysis of the N-terminal exodomain. Upon proteolysis, the newly formed n terminus acts as a tethered ligand that activates the receptor and initiates signaling cascades through multiple g proteins (galfaq, galfai, and galfa12/13). | SIGNOR-196006 |
O00238 | Q13253 | 0 | binding | down-regulates activity | 0.599 | Noggin binds the domain that is re-quired for bmp-7 to interact with bmp type i and type ii receptors.Noggin Inhibits bmp by blocking the molecular interfaces of the binding epitopes for both type i and type ii receptors (pmid 12478285) | SIGNOR-192802 |
Q13131 | Q15831 | 0 | phosphorylation | up-regulates activity | 0.599 | The AMP-activated protein kinase (AMPK) is a critical regulator of energy balance at both the cellular and whole-body levels. Two upstream kinases have been reported to activate AMPK in cell-free assays, i.e., the tumor suppressor LKB1 and calmodulin-dependent protein kinase kinase. | SIGNOR-139297 |
Q12888 | P06493 | 0 | phosphorylation | down-regulates activity | 0.599 | Nuclear import of 53BP1 is required for proper localization of 53BP1 and maintenance of genome integrity. 53BP1 has a classical bipartite nuclear localization signal (NLS) of sequence 1666-GKRKLITSEEERSPAKRGRKS-1686. Ser1678 within the 53BP1 NLS can be phosphorylated by CDK1/cyclin B, and a phosphomimetic substitution of Ser1678 with aspartate has been shown to negatively regulate nuclear import of 53BP1. | SIGNOR-264412 |
P46734 | Q99683 | 0 | phosphorylation | up-regulates activity | 0.599 | Ask1 is a member of a mapkkk family and functions as an upstream kinase engaged in c-jun nh2-terminal kinase (jnk)/p38 signaling via the phosphorylation and activation of mapkks, such as mkk3, -4, -6, and -7 | SIGNOR-161763 |
P53350 | Q96GD4 | 0 | phosphorylation | up-regulates activity | 0.599 | Aurora B phosphorylates PLK1 on Thr210 to activate its kinase activity at the kinetochores during mitosis.|Thus, we conclude that Aurora B indirectly promotes the phosphorylation of MCAK on Ser715 at the kinetochores through phosphorylation of PLK1 at Thr210 and its ensuing activation. | SIGNOR-279358 |
P04275 | Q76LX8 | 0 | cleavage | down-regulates activity | 0.599 | Proteolytic degradation of VWF by ADAMTS-13 downregulates the proinflammatory potential of VWF. | SIGNOR-251966 |
Q13535 | P00519 | 0 | phosphorylation | up-regulates | 0.599 | C-abl can phosphorylate atr on y291 and y310 and this phosphorylation appears to have a positive role in atr activation under genotoxic stress. | SIGNOR-167632 |
Q14145 | Q9NY33 | 0 | cleavage | down-regulates quantity by destabilization | 0.599 | The influence of DPP3 on the Keap1-Nrf2/ARE signal pathway suggest a direct involvement of DPP3 in the oxidative stress response [8,14,31,53,99,100]. It was shown that DPP3 competes with Nrf2 through the ETGE motif to bind to Keap1 and consequently enhances the translocation of Nrf2 to the nucleus, thereby driving the expression of an array of genes encoding antioxidative enzymes [99]. More specifically, binding of DPP3 to Keap1 releases Nrf2, and thus, prevents its degradation through the 26S proteasome | SIGNOR-268464 |
P56945 | Q13882 | 0 | phosphorylation | up-regulates | 0.599 | Protein-tyrosine kinase 6 promotes peripheral adhesion complex formation and cell migration by phosphorylating p130 crk-associated substrate. Tyrosine residues 165 and 664 of p130cas were both phosphorylated by ptk6 in vitro | SIGNOR-177242 |
O43541 | Q99717 | 0 | transcriptional regulation | up-regulates quantity | 0.599 | 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-268940 |
P35222 | Q05513 | 0 | phosphorylation | down-regulates quantity by destabilization | 0.599 | Yap and β-catenin are direct substrates of PKCζ. Similar MS/MS analysis to map the sites phosphorylated in β-catenin by PKCζ identified S45 and several sites of low abundance that included S552 and S675 (Figure S3C). | SIGNOR-276880 |
P01024 | P08311 | 0 | cleavage | up-regulates activity | 0.599 | Plasma membrane elastase and cathepsin G from U937 cells cleave C3 into C3a- and C3b-like fragments; further incubation leads to C3c- and C3dg-like fragments, as judged from SDS-PAGE analysis of the digests. Sequencing of the C3b-like fragment purified by reverse phase chromatography indicates that initial cleavage of C3 by purified cathepsin G occurs at two positions in the amino-terminal part of the alpha-chain, at a Arg-Ser bond located between residues 748 and 749 and at a Leu-Asp bond between residues 751 and 752. | SIGNOR-256348 |
P60484 | P42685 | 0 | phosphorylation | up-regulates quantity by stabilization | 0.599 | Rak phosphorylates PTEN on Tyr 336 to prevent its protein degradation. In this study, we demonstrate that the Rak tyrosine kinase physically interacts with PTEN and phosphorylates PTEN on Tyr336. Knockdown of Rak enhanced the binding of PTEN to its E3 ligase NEDD4-1 and promoted PTEN polyubiquitination, leading to PTEN protein degradation. | SIGNOR-275458 |
P62136 | Q9UD71 | 0 | binding | down-regulates activity | 0.599 | DARPP-32 (dopamine and cyclic AMP-regulated phospho-protein, relative molecular mass 32,000) is converted into an inhibitor of protein phosphatase 1 when it is phosphorylated by protein kinase A (PKA) at threonine 34.‚ | SIGNOR-264957 |
P61020 | Q5S007 | 0 | phosphorylation | up-regulates activity | 0.599 | Using recombinant proteins, we show here that LRRK2 phosphorylates Rab5b at its Thr6 residue in in vitro kinase assays with mass spectrophotometry analysis. Phosphorylation of Rab5b by LRRK2 on the threonine residue was confirmed by western analysis using cells stably expressing LRRK2 G2019S. The phosphomimetic T6D mutant exhibited stronger GTPase activity than that of the wild-type Rab5b. In addition, phosphorylation of Rab5b by LRRK2 also exhibited GTPase activity stronger than that of the unphosphorylated Rab5b protein. | SIGNOR-276873 |
Q00987 | Q13263 | 0 | binding | up-regulates activity | 0.598 | we present evidence that MDM2 interacts with the nuclear corepressor KAP1. MDM2 interaction with nuclear corepressor KAP1 contributes to p53 inactivation. | SIGNOR-240405 |
P15498 | O15524 | 0 | binding | down-regulates quantity by destabilization | 0.598 | SOCS1 stimulates the polyubiquitination of VAV proteins in vivo, which was stabilized by proteasomal inhibitors. These results suggest that SOCS1 programs VAV degradation by acting as a substrate-specific recognition component of a VCB-like ubiquitin ligase complex. | SIGNOR-272559 |
O15360 | Q13535 | 0 | phosphorylation | up-regulates | 0.598 | The s1449a mutant failed to completely correct a variety of fa-associated phenotypes. The dna damage response is coordinated by phosphorylation events initiated by apical kinases atm (ataxia telangectasia mutated) and atr (atm and rad3-related), and atr is essential for proper fa pathway function. Serine 1449 is in a consensus atm/atr site | SIGNOR-182953 |
O95997 | P06493 | 0 | phosphorylation | up-regulates | 0.598 | Hpttg is phosphorylated by cdc2 at ser165 these results suggest that hpttg is induced by, and may have a role in, regulatory pathways involved in the control of cell proliferation. | SIGNOR-74619 |
P07550 | O14745 | 0 | binding | up-regulates activity | 0.598 | The Na+/H+ exchanger regulatory factor (NHERF) binds to the tail of the beta2-adrenergic receptor and plays a role in adrenergic regulation of Na+/H+ exchange. NHERF contains two PDZ domains, the first of which is required for its interaction with the beta2 receptor. | SIGNOR-262598 |
O14950 | O75116 | 0 | phosphorylation | up-regulates activity | 0.598 | In addition, an in vitro kinase assay with mixed recombinant GST-ROCK2 and MLC2 revealed that ROCK2 phosphorylated WT MLC2, but not MLC2 S15A mutant, indicating that it phosphorylates MLC2 at S15 in vitro (XREF_FIG). | SIGNOR-279103 |
O14640 | Q9ULV1 | 0 | binding | up-regulates activity | 0.598 | Through study of FZD4 and its associated ligand Norrin, we report that a minimum of three residues distal to the KTXXXW motif in the C-terminal tail of Frizzled-4 are essential for DVL recruitment and robust Lef/Tcf-dependent transcriptional activation in response to Norrin. | SIGNOR-258955 |
P01116 | Q13671 | 0 | binding | up-regulates | 0.598 | We demonstrate that the ras effector protein rin1 binds to activated ras with an affinity (k(d), 22 nm) similar to that observed for raf1. | SIGNOR-113970 |
P35222 | Q13616 | 0 | ubiquitination | down-regulates quantity by destabilization | 0.598 | These results indicate that the cul1/skp1/beta-trcp complex forms a ubiquitin ligase that mediates the degradation of beta-catenin. | SIGNOR-64499 |
Q9H1Y0 | Q8IZQ1 | 0 | binding | up-regulates quantity | 0.598 | Alfy is recruited to intracellular inclusions and scaffolds a complex between p62(SQSTM1)-positive proteins and the autophagic effectors Atg5, Atg12, Atg16L and LC3. Alfy directly interacts with Atg5 and can be found in a complex with Atg5, Atg12 and Atg16L | SIGNOR-266791 |
P17676 | P84022 | 0 | binding | down-regulates activity | 0.597 | Thus, repression of the activity of C/EBPs by Smad3/4 at C/EBP binding sites inhibited transcription from the PPAR2 and leptin promoters | SIGNOR-250567 |
P49841 | Q05513 | 0 | phosphorylation | down-regulates | 0.597 | Phospho-gsk3b-specific antibodies also revolved that lkb1 regulates gsk3b phosphorylation at a known inhibitory site, serine-9. This localized phosphorylation is cdc42 and pkc-zeta-dependent. | SIGNOR-119889 |
P53667 | Q8WYL5 | 0 | dephosphorylation | down-regulates activity | 0.597 | In addition to its cofilin\u2013phosphatase activity, SSH1 can also dephosphorylate LIMK1 and LIMK2, although LIMK1 is a better substrate than LIMK2 [63] .|SSH1 suppresses the kinase activity of LIMK1 toward cofilin by dephosphorylation at Thr 508 in the kinase catalytic domain and other autophosphorylated residues [63]. | SIGNOR-277096 |
Q08828 | P04899 | 0 | binding | down-regulates activity | 0.597 | Adenylate cyclase is regulated by stimulatory hormones through Gs(alpha s beta gamma) and inhibitory hormones through Gi(alpha i beta gamma) | SIGNOR-256499 |
P49336 | Q92585 | 0 | binding | up-regulates | 0.597 | Mastermind recruits cycc:cdk8 to phosphorylate the notch icd and coordinate activation with turnover | SIGNOR-130715 |
O15350 | P0C2W1 | 0 | binding | down-regulates quantity by destabilization | 0.597 | The F-box protein FBXO45 promotes the proteasome-dependent degradation of p73.Importantly, SCFFBXO45 ubiquitylates p73 both in vivo and in vitro. Expression of Cul1 dominant negative mutant, but not Cul2, Cul3, Cul4 and Cul5 dominant negative mutants, increased p73 levels (Figure 1c) to an extent similar to that observed in the ts41 cell line at not permissive temperature, suggesting that a Cul1-associated activity is required for p73 protein stability. | SIGNOR-271876 |
P84022 | Q9Y6X2 | 0 | binding | up-regulates activity | 0.597 | We have further shown that PIAS3, Smad3, and p300 can form a ternary complex, which is significantly increased by TGF-_ treatment. Taken together, these results suggest that PIAS3 stimulates Smad transcriptional activity through formation of a complex with Smad proteins and p300/CBP. | SIGNOR-217725 |
Q07869 | P19793 | 0 | binding | up-regulates | 0.597 | Although the three ppar subtypes are closely related and bind to similar dna response elements as heterodimers with the 9-cis retinoic acid receptor rxr, each subserves a distinct physiology | SIGNOR-105345 |
O43586 | P00519 | 0 | phosphorylation | up-regulates activity | 0.597 | PSTPIP1 was phosphorylated by c-Abl. Tyr-344 is a major c-Abl phosphorylation site.PSTPIP1 was able to bridge c-Abl to the PEST-type PTPs. | SIGNOR-251431 |
Q05655 | P06241 | 0 | phosphorylation | up-regulates activity | 0.597 | In conclusion, our in vitro data and previous report ( xref ) demonstrate that Fyn phosphorylation of Y311 on PKC\u03b4 activates the apoptotic signaling cascade in DAergic neurons in response to neurotoxic insults. | SIGNOR-279737 |
Q99683 | P53041 | 0 | dephosphorylation | down-regulates activity | 0.597 | After exposure of cells to H2O2, ASK1 is transiently activated by autophosphorylation at Thr845. The protein then associates with PP5 (protein serine/threonine phosphatase 5), which inactivates ASK1 by dephosphorylation of Thr845. | SIGNOR-248540 |
P11166 | P04637 | 0 | transcriptional regulation | down-regulates quantity by repression | 0.597 | P53 regulates basal expression of AIF and SCO2 and facilitates oxidative phosphorylation. The expression of GLUT1, GLUT4, and HK2 is negatively regulated by p53, whereas TIGAR expression is induced by p53. The net result of p53-mediated regulation of these glycolytic enzymes is the suppression of glycolysis. In addition, p53 directly binds and inhibits G6PD activity and downregulates the pentose phosphate pathway. | SIGNOR-267464 |
P50148 | Q9HBW0 | 0 | binding | up-regulates activity | 0.597 | 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-257382 |
O43318 | Q12933 | 0 | ubiquitination | up-regulates activity | 0.597 | Tumor necrosis factor receptor-associated factors 2 and 6 (traf2 and -6) act as the ubiquitin e3 ligases to mediate lys63-linked tak1 polyubiquitination at the lys158 residue in vivo and in vitro. Lys(63)-linked TAK1 polyubiquitination at the Lys(158) residue is required for TAK1-mediated IKK complex recruitment. | SIGNOR-162638 |
P23443 | P28482 | 0 | phosphorylation | up-regulates | 0.596 | Erk phosphorylates multiple cytoplasmatic and cytoskeletal proteins, including mapk-activated protein kinases and the ribosomal p70-s6 kinase | SIGNOR-28800 |
P62136 | Q9UQ13 | 0 | binding | up-regulates activity | 0.596 | Using a proteomics approach, we have identified a complex comprised of Shoc2/Sur-8 and the catalytic subunit of protein phosphatase 1 (PP1c) as a highly specific M-Ras effector. M-Ras targets Shoc2-PP1c to stimulate Raf activity by dephosphorylating the S259 inhibitory site | SIGNOR-251647 |
P40763 | Q05655 | 0 | phosphorylation | up-regulates | 0.596 | Abrogation of pkcdelta activity inhibited insulin-induced stat3 phosphorylation, pkcdelta-stat3 association and nuclear translocation. | SIGNOR-143828 |
P10636 | Q9UQM7 | 0 | phosphorylation | down-regulates activity | 0.596 | We found that when tau was first phosphorylated by A-kinase, C-kinase, cdk5, or CaM kinase II and then by GSK-3, its binding to microtubules was inhibited by 45, 61, 78, and 79%, respectively. Further, the kinase combinations cdk5/GSK-3 and CaM kinase II/GSK-3 rapidly phosphorylated the sites Thr 231 and Ser 235. When these sites were individually replaced by Ala and the phosphorylation experiments repeated, tau binding to microtubules was inhibited by 54 and 71%, respectively. By comparison, when Ser 262 was replaced by Ala, tau binding to microtubules was inhibited by only 8% after phosphorylation by CaM kinase II. | SIGNOR-249315 |
Q9HBY8 | O15530 | 0 | phosphorylation | up-regulates activity | 0.596 | SGK2 and SGK3 are activated in vitro by PDK1, albeit more slowly than SGK1, and their activation is accompanied by the phosphorylation of Thr(193) and Thr(253) respectively. The PDK1-catalysed phosphorylation and activation of SGK2 and SGK3, like SGK1, is greatly potentiated by mutating Ser(356) and Ser(419) respectively to Asp, these residues being equivalent to the C-terminal phosphorylation site of PKB. | SIGNOR-250277 |
P50548 | P28482 | 0 | phosphorylation | up-regulates | 0.596 | The experiments presented here indicate that erf is regulated during nuclear import and/or export and that this process depends on its phosphorylation by erks our analysis indicates that in addition to t526 (position 7), s161 (position 2), s246 (position 3), and s251 (position 4) are also phosphorylated in vitro by erk2 and in vivo after mitogenic stimulation (fig. 3a). | SIGNOR-67524 |
P36894 | Q6KF10 | 0 | binding | up-regulates | 0.596 | We found that transfection of small hairpin rna for bmprii and actriia in mc3t3 cells suppressed the signaling of gdf6, gdf7, and bmp10. | SIGNOR-139090 |
Q9C0D5 | P78352 | 0 | binding | up-regulates activity | 0.596 | In the present study, we provide evidence that TANC1 and its close relative TANC2 regulate dendritic spines and excitatory synapses. our results indicate that TANC-dependent spine/synapse maintenance requires TANC binding to PSD-95, which promotes synaptic localization of TANC proteins. Thus, it is likely that interaction with PSD-95 concentrates TANC proteins at synapses, where they play a role in mediating PSD-95-dependent maintenance of spines and synapses. | SIGNOR-266894 |
P78352 | Q96PV0 | 0 | binding | up-regulates activity | 0.596 | The reversible removal of AIDA-1 from the PSD core under excitatory conditions is similar to the redistribution of another abundant PSD protein, SynGAP. Both SynGAP-alpha1 and AIDA-1 are known to bind PSD-95. | SIGNOR-264229 |
Q13322 | Q6Y7W6 | 0 | binding | up-regulates activity | 0.596 | We demonstrated that, in cultured cells and mammalian brains, GIGYF2 interacts and colocalises with Grb10, promoting ligand‐induced ubiquitination of IGF‐1R, and thereby regulates receptor degradation | SIGNOR-260057 |
P15884 | Q02363 | 0 | binding | down-regulates activity | 0.596 | All three Ids bound with high affinity to E proteins .Each Id was able to disrupt the ability of E protein-MyoD complexes to transactivate from a muscle creatine kinase reporter construct in vivo. | SIGNOR-241376 |
Q6UVJ0 | Q66GS9 | 0 | binding | up-regulates activity | 0.596 | In this study, we demonstrate that the human microcephaly protein, CEP135, directly interacts with hSAS-6 via its carboxyl-terminus and with MTs via its amino-terminus. Unexpectedly, CEP135 also interacts with another microcephaly protein CPAP via its amino terminal domain. Depletion of CEP135 not only perturbed the centriolar localization of CPAP, but also blocked CPAP-induced centriole elongation. We propose that CEP135 may serve as a linker protein that directly connects the central hub protein, hSAS-6, to the outer MTs, and suggest that this interaction stabilizes the proper cartwheel structure for further CPAP-mediated centriole elongation. | SIGNOR-269676 |
P11912 | P06241 | 0 | phosphorylation | up-regulates activity | 0.596 | Lyn and Fyn phosphorylated the CD79a cytoplasmic portion of the fusion proteins well, with >80% of phosphorylation occurring at Y182. CD79a and CD79b function as transducers of B cell antigen receptor signals via a cytoplasmic sequence, termed the immunoreceptor tyrosine-based activation motif (ITAM). | SIGNOR-251153 |
Q12888 | P53350 | 0 | phosphorylation | down-regulates activity | 0.596 | 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 |Addition of the inhibitors for PLK1 and the p38 MAPK leads to a complete loss of pT1609/pS1618 signal within 3 hr in mitotic cells | SIGNOR-264413 |
P40763 | Q12778 | 0 | binding | down-regulates activity | 0.596 | FoxO1, which is up-regulated during early stages of diet-induced leptin resistance, directly interacts with STAT3 and prevents STAT3 from binding to specificity protein 1 (SP1)-pro-opiomelanocortin (POMC) promoter complex, and thereby inhibits STAT3-mediated regulation of POMC transcription. | SIGNOR-263496 |
P00533 | Q9Y6I3 | 0 | relocalization | down-regulates | 0.596 | Epsin 1 is involved in recruitment of ubiquitinated egf receptors into clathrin-coated pits this supports the contention that epsin 1 promotes endocytosis of the ubiquitinated egfr. | SIGNOR-182562 |
O14920 | Q13233 | 0 | phosphorylation | up-regulates activity | 0.595 | These results suggested that IKK\u03b2 was a likely substrate for MEKK1 and that MEKK1 phosphorylation of IKK\u03b2 increased its kinase activity. | SIGNOR-279339 |
Q8IVP5 | O75385 | 0 | phosphorylation | up-regulates activity | 0.595 | Here, we show that ULK1 is upregulated and translocates to fragmented mitochondria upon mitophagy induction by either hypoxia or mitochondrial uncouplers. At mitochondria, ULK1 interacts with FUNDC1, phosphorylating it at serine 17, which enhances FUNDC1 binding to LC3. | SIGNOR-273606 |
O43524 | P27361 | 0 | phosphorylation | down-regulates quantity by destabilization | 0.595 | Phosphorylation of foxo3a by erk1/2 at residues ser 294, ser 344 and ser 425 increases foxo3amdm2 interaction and enhances foxo3a degradation via an mdm2-dependent ubiquitin-proteasome pathway | SIGNOR-184569 |
O75197 | O14905 | 0 | binding | up-regulates | 0.595 | Wnt proteins bind to the frizzled receptors and lrp5/6 co-receptors, and through stabilizing the critical mediator betBeta-catenin, initiate a complex signaling cascade that plays an important role in regulating cell proliferation and differentiation. | SIGNOR-132114 |
Q12778 | Q13043 | 0 | phosphorylation | up-regulates | 0.595 | Bonni and coworkers demonstrated that mst1 can phosphorylate foxo3 (and subsequently, foxo1) principally ser207 (ser212 in foxo1), a conserved site in the forkhead domain. This phosphorylation interdicts 14-3-3 binding, promotes foxo nuclear residence and transcriptional activity. The other major signaling modules that directly regulate the activity of the foxo factors include the stress-activated jun-n-terminal kinase (jnk), the mammalian ortholog of the ste20-like protein kinase (mst1), and the deacetylase sirt1. | SIGNOR-191847 |
P62166 | Q9NZN1 | 0 | binding | up-regulates activity | 0.595 | IL1 receptor accessory protein like, a protein involved in X-linked mental retardation, interacts with Neuronal Calcium Sensor-1 and regulates exocytosis. our data show that IL1RAPL interacts only with NCS-1 through its specific C-terminal domain. The functional relevance of IL1RAPL activity was further supported by the inhibitory effect on exocytosis in PC12 cells overexpressing IL1RAPL. Taken together, our data suggest that IL1RAPL may regulate calcium-dependent exocytosis and provide insight into the understanding of physiopathological mechanisms underlying cognitive impairment resulting from IL1RAPL dysfunction. | SIGNOR-263962 |
P11388 | P68400 | 0 | phosphorylation | down-regulates quantity by destabilization | 0.595 | This study also reports the novel finding that topoIIα may be a target of GSK3β phosphorylation. Evidence suggests that CK2 serves as a priming kinase, through phosphorylation at Ser1365, for GSK3β-mediated phosphorylation at Ser1361. | SIGNOR-276300 |
Q8ND76 | P06493 | 0 | phosphorylation | down-regulates activity | 0.595 | Therefore, CDK1 may trigger CFP1 degradation through some indirect mechanisms rather than CFP1 phosphorylation.|This result suggests that, although CDK1 triggers both phosphorylation and degradation of CFP1 protein, phosphorylation of CFP1 by CDK1 is not a prerequisite for its degradation during cell division. | SIGNOR-279012 |
Q14534 | Q12772 | 0 | transcriptional regulation | up-regulates quantity by expression | 0.595 | The processed SREBP2, designated nuclear SREBP2 (nSREBP2), then enters the nucleus as a homodimer, binds to the sterol regulatory element (SRE) sequence in the promoters of target genes, including HMGCR and SQLE (encoding squalene monooxygenase), and upregulates their transcription | SIGNOR-265162 |
Q05397 | P00533 | 0 | phosphorylation | up-regulates | 0.595 | In this study, we demonstrate that growth factor receptors including hepatocyte growth factor receptor met, epidermal growth factor receptor, and platelet-derived growth factor receptor directly phosphorylate fak on tyr194 in the ferm domain collectively, this study provides the first example to explain how fak is activated by receptor tyrosine kinases. | SIGNOR-167646 |
P37173 | Q9HAU4 | 0 | ubiquitination | down-regulates activity | 0.595 | Smurf1 and smurf2 are e3 ubiquitin ligases known to suppress tgf-beta signaling through degradation of smads and receptors for tgf-beta and bmps. | SIGNOR-195681 |
Q08828 | P08754 | 0 | binding | down-regulates | 0.595 | Concentration-dependent inhibition of adenylyl cyclases by purified Gi alpha subunits is described. Activated Gi alpha but not G(o) alpha was effective, and myristoylation of Gi alpha was required | SIGNOR-38029 |
P46527 | P00519 | 0 | 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 |
P03372 | P23443 | 0 | phosphorylation | up-regulates | 0.595 | Serine 167 is the major phosphorylation site on the human estrogen receptor. Phosphorylation is mediated by casein kinase ii. | SIGNOR-34117 |
P12755 | Q6ZNA4 | 0 | ubiquitination | down-regulates | 0.595 | On tgf-beta treatment, the e3 ubiquitin ligase arkadia mediates degradation of ski in a smad-dependent manner | SIGNOR-178598 |
P62714 | O43815 | 0 | binding | up-regulates activity | 0.595 | The striatin family proteins interact with the structural (A) and catalytic (C) subunits of the protein phosphatase, PP2A, and are also termed the B‴ family of PP2A subunits (4). Within heterotrimeric PP2A complexes, striatins function as one of many regulatory B subunits thought to be responsible for substrate selection and localization of PP2A isoforms | SIGNOR-261700 |
Q06609 | P24941 | 0 | phosphorylation | down-regulates quantity by destabilization | 0.595 | Phosphorylation of the BRCA2 C-terminal RAD51 binding site by CDK2 promotes RAD51 filament disassembly, leading to nucleolitic cleavage of newly synthesized DNA and compromised fork integrity. | SIGNOR-280213 |
P24385 | Q13309 | 0 | binding | down-regulates quantity by destabilization | 0.594 | We show that SK-UT-1B cells express a novel splice variant of Skp2 that localizes to the cytoplasm and that cyclin D1 ubiquitination takes place in the nucleus. We propose that the translocation of Skp2 into the nucleus is required for the ubiquitination of cyclin D1 and that the absence of the SCF(Skp2) complex in the nucleus of SK-UT-1B cells is the mechanism underlying the ubiquitination defect observed in this cell line. | SIGNOR-272575 |
Q02556 | P17947 | 0 | binding | up-regulates activity | 0.594 | We found that tyrosine phosphorylated ICSBP activates CYBB and NCF2 transcription, during late myeloid differentiation, by interacting with PU.1, IRF1 and CBP. | SIGNOR-222880 |
Q9BUB5 | P28482 | 0 | phosphorylation | up-regulates | 0.594 | We have identified a new subfamily of murine serine/threonine kinases, whose members, map kinase-interacting kinase 1 (mnk1) and mnk2, bind tightly to the growth factor-regulated map kinases, erk1 and erk2erk and p38 phosphorylate mnk1 and mnk2, which stimulates their in vitro kinase activity toward a substrate, eukaryotic initiation factor-4e (eif-4e). | SIGNOR-48298 |
P16220 | Q9UQM7 | 0 | phosphorylation | down-regulates | 0.594 | Phosphorylation of creb1 at ser142 and ser143 is selectively activated by ca(2+) influx;phosphorylation of ser142 and ser143, disrupts the interaction of creb with its cofactor cbp. Phosphorylation of serine 142 in creb by camkii leads to dissociation of the creb dimer. | SIGNOR-82501 |
O14733 | Q99683 | 0 | phosphorylation | up-regulates | 0.594 | Ask1 is a member of a mapkkk family and functions as an upstream kinase engaged in c-jun nh2-terminal kinase (jnk)/p38 signaling via the phosphorylation and activation of mapkks, such as mkk3, -4, -6, and -7 | SIGNOR-161766 |
Q9Y4K3 | Q01638 | 0 | binding | up-regulates activity | 0.594 | As shown in Figure 3D, MyD88, IRAK, IRAK4, and TRAF6 are all recruited to ST2 upon IL-33 stimulation. | SIGNOR-277707 |
Q15910 | P31749 | 0 | phosphorylation | down-regulates activity | 0.594 | Enhancer of zeste homolog 2 (ezh2) is a methyltransferase that plays an important role in many biological processes through its ability to trimethylate lysine 27 in histone h3. Here, we show that akt phosphorylates ezh2 at serine 21 and suppresses its methyltransferase activity by impeding ezh2 binding to histone h3 | SIGNOR-141043 |
P55957 | P45983 | 0 | phosphorylation | up-regulates activity | 0.594 | (b) Phosphorylation of Bid at Thr59 by JNK1 and JNK2 (in vitro kinase assay). | SIGNOR-279076 |
P45985 | P31749 | 0 | phosphorylation | down-regulates | 0.594 | Akt phosphorylated sek1 on serine 78. | SIGNOR-236494 |
Q12772 | Q14703 | 0 | cleavage | up-regulates activity | 0.594 | We present evidence that SKI-1 processes peptides mimicking the cleavage sites of the SKI-1 prosegment, pro-brain-derived neurotrophic factor, and the sterol regulatory element-binding protein SREBP-2 | SIGNOR-267496 |
P17947 | Q99684 | 0 | binding | down-regulates activity | 0.594 | Our data demonstrate that GFI-1 physically interacts with PU.1, repressing PU.1-dependent transcription. This repression is functionally significant, as GFI-1 blocked PU.1-induced macrophage differentiation of a multipotential hematopoietic progenitor cell line. | SIGNOR-256043 |
Q9UDT6 | Q7Z460 | 0 | binding | up-regulates activity | 0.594 | CLIP-associating protein (CLASP) 1 and CLASP2 are mammalian microtubule (MT) plus-end binding proteins, which associate with CLIP-170 and CLIP-115.|We demonstrate that the middle part of CLASPs binds directly to EB1 and to MTs. | Both EB1- and cortex-binding domains of CLASP are required to promote MT stability. | SIGNOR-265092 |
P08151 | Q13547 | 0 | deacetylation | up-regulates activity | 0.594 | Here, we identify a mechanism whereby Hh signalling is regulated, in which acetylation of Gli1 at Lys 518 represents a transcriptional inhibitory switch, while its HDAC1-mediated deacetylation is responsible for transcriptional activation. | SIGNOR-253544 |
P30989 | P34947 | 0 | phosphorylation | up-regulates activity | 0.594 | Here we report the unique phosphorylation\nof NTSR1 by GRK2 and GRK5, which belong to the GRK2 and GRK4 subfamilies,\nrespectively. | SIGNOR-278234 |
P43405 | P09769 | 0 | phosphorylation | up-regulates activity | 0.594 | Fgr associates with Fc\u03b5RI and phosphorylates Syk in antigen-stimulated mast cells.|The overexpression of Fgr stimulates Syk, Syk dependent signaling molecules, and degranulation in RBL-2H3 cells and BMMCs. | SIGNOR-279332 |
Q8IZQ1 | Q9BXW4 | 0 | binding | up-regulates activity | 0.594 | Here, we show that ALFY binds selectively to LC3C and the GABARAPs through a LIR in its WD40 domain. Binding of ALFY to GABARAP is indispensable for its recruitment to LC3B-positive structures and, thus, for the clearance of certain p62 structures by autophagy. | SIGNOR-266795 |
Q15796 | Q9GZV5 | 0 | binding | up-regulates | 0.593 | Taz has been shown to interact with smad2 and smad3 through its coiled-coil region, and to be important in maintaining the nuclear localization of smad2 and smad3 as well as the expression of their target genes in response to tgf-b signaling and, thus, in the maintenance of human esc self-renewal. | SIGNOR-169835 |
P46937 | P31749 | 0 | phosphorylation | down-regulates | 0.593 | One protein that associates with 14-3-3 in an akt-dependent manner is shown here to be the yes-associated protein (yap), which is phosphorylated by akt at serine 127, leading to binding to 14-3-3. Akt promotes yap localization to the cytoplasm, resulting in loss from the nucleus where it functions as a coactivator of transcription factors including p73. | SIGNOR-252593 |
Q8NHV4 | O00444 | 0 | phosphorylation | up-regulates activity | 0.593 | We found that PLK4-mediated phosphorylation of NEDD1 at its S325 amino acid residue directly promotes both NEDD1 binding to SAS-6 and recruiting SAS-6 to the centrosome. |Collectively, our results demonstrate that PLK4-regulated NEDD1 facilitates initiation of the cartwheel assembly and of daughter centriole biogenesis in mammals. | SIGNOR-272996 |
P45984 | P45983 | 0 | phosphorylation | up-regulates | 0.593 | Our studies revealed a novel mechanism in which phosphorylation of jnk2 is mediated by jnk1 before phosphorylation of p53, and then p53 is directly phosphorylated by jnk2 at ser6. | SIGNOR-155205 |
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