IdA stringlengths 6 21 | IdB stringlengths 6 21 | labels int64 0 2 | mechanism stringclasses 40 values | effect stringclasses 10 values | score float64 0.1 0.99 ⌀ | sentence stringlengths 10 1.63k ⌀ | signor_id stringlengths 12 14 |
|---|---|---|---|---|---|---|---|
P67775 | O96017 | 1 | dephosphorylation | up-regulates activity | 0.432 | Protein phosphatase 2A interacts with Chk2 and regulates phosphorylation at Thr-68 after cisplatin treatment of human ovarian cancer cells|In response to DNA damage, Chk2 is initially phosphorylated at Thr-68, which leads to its full activation. | SIGNOR-248617 |
P19474 | Q9C035 | 1 | monoubiquitination | up-regulates quantity | 0.344 | Here, we show that TRIM5alpha functions as a RING-finger-type E3 ubiquitin ligase both in vitro and in vivo and ubiquitinates itself in cooperation with the E2 ubiquitin-conjugating enzyme UbcH5B. Thus, the ubiquitination of TRIM5alpha is catalyzed by itself and Ro52. Unexpectedly, although TRIM5alpha is ubiquitinated, our results have revealed that the proteasome inhibitors MG115 and MG132 do not stabilize it in HeLa cells, suggesting that the ubiquitination of TRIM5alpha does not lead to proteasomal degradation. Importantly, TRIM5alpha is clearly conjugated by a single ubiquitin molecule (monoubiquitination). Our monoubiquitin-fusion assay suggests that monoubiquitination is a signal for TRIM5alpha to translocate from cytoplasmic bodies to the cytoplasm. | SIGNOR-271672 |
P09874 | P04637 | 1 | relocalization | up-regulates activity | 0.559 | We identify the major poly(ADP-ribosyl)ated sites of p53 by PARP-1 and find that PARP-1-mediated poly(ADP-ribosyl)ation blocks the interaction between p53 and the nuclear export receptor Crm1, resulting in nuclear accumulation of p53. These findings molecularly link PARP-1 and p53 in the DNA-damage response, providing the mechanism for how p53 accumulates in the nucleus in response to DNA damage.|PARP-1 is super-activated by binding to damaged DNA, and poly(ADP-ribosyl)ates p53. Poly(ADP-ribosyl)ation probably induces a structural change that mask the NES, and thus Crm1 can no longer target p53 to the nuclear export machinery, resulting in accumulation of p53 in the nucleus. | SIGNOR-261321 |
P09619 | Q13237 | 0 | phosphorylation | down-regulates activity | 0.272 | Secretory PKG II inhibited PDGF‐BB ‐induced PDGFRβ activation via phosphorylating its Ser254. | SIGNOR-277577 |
P09211 | Q05513 | 0 | phosphorylation | up-regulates activity | 0.2 | Peptide phosphorylation analyses and both phosphorylation and enzyme kinetic studies with GSTP1 proteins mutated at candidate amino acid residues established Ser-42 and Ser-184 as putative phospho-acceptor residues for both kinases in the GSTP1 protein. Together, these findings show PKA- and PKC-dependent phosphorylation as a significant post-translational mechanism of regulation of GSTP1 function. Together, these results further support S42 and S184 as major phosphor-acceptor residues for PKA and PKC and suggest that the increased activity of the phospho-GSTP1 was not simply a consequence of the negative charge introduced in the GSTP1 protein by the phosphate group.All eight PKC isoforms, PKC-α, PKC-βI, PKC-βII, PKC-ε, PKC-γ, PKC-η, and PKC-ζ phosphorylated the GSTP1 protein efficiently | SIGNOR-276017 |
Q96D59 | O14763 | 1 | polyubiquitination | down-regulates quantity by destabilization | 0.2 | RNF183 mediated K63-linked ubiquitination and lysosomal degradation of DR5. | SIGNOR-272212 |
Q16650 | O14936 | 2 | binding | up-regulates | 0.458 | Here we report that, through its guanylate kinase domain, CASK interacts with Tbr-1, a T-box transcription factor that is involved in forebrain development. CASK enters the nucleus and binds to a specific DNA sequence (the T-element) in a complex with Tbr-1. CASK acts as a coactivator of Tbr-1 to induce transcription of T-element containing genes, including reelin, a gene that is essential for cerebrocortical development. | SIGNOR-266835 |
P27361 | P62136 | 0 | dephosphorylation | down-regulates | 0.444 | P-erk1/2 proteins were efficiently dephosphorylated in vitro by protein phosphatases 1 and 2a (pp1/2a) and mapk phosphatase 3 (mkp3). the dual specificity phosphatases that specifically dephosphorylate and inactivate the p-erk1/2 are called mapk phosphatases | SIGNOR-103155 |
Q92626 | O95863 | 0 | transcriptional regulation | down-regulates quantity by repression | 0.2 | TGF-β1 induced Snai1 binding to the PXDN promoter (as assessed by chromatin immunoprecipitation-PCR) and significantly repressed luciferase reporter gene expression, as did Snai1 overexpression. | SIGNOR-265249 |
P06493 | P26358 | 1 | phosphorylation | up-regulates | 0.3 | We report that cyclin-dependent kinases (cdks) 1, 2 and 5 can phosphorylate ser154 of human dnmt1 in vitro. Further evidence of phosphorylation of endogenous dnmt1 at position 154 by cdks is also found in 293 cells treated with roscovitine, a specific inhibitor of cdk1, 2 and 5 | SIGNOR-173677 |
P45984 | P16104 | 1 | phosphorylation | up-regulates | 0.2 | H2ax interacts with numerous proteins required for dna damage signaling and repair when phosphorylated on ser-140. Phosphorylation of ser-140 (h2ax139ph) in response to ionizing radiation is mediated by both atm and prkdc. Our data showed that h2ax is phosphorylated by uva-activated jnk. | SIGNOR-160210 |
Q05655 | P23470 | 0 | dephosphorylation | up-regulates activity | 0.2 | 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-254716 |
P16615 | P49841 | 0 | phosphorylation | down-regulates activity | 0.283 | GSK3β-dependent phosphorylation of SERCA2 at serine 663 in human and mouse hearts. Phosphorylation of SERCA2 at serine 663 regulates SERCA2 activity. | SIGNOR-277886 |
Q9H2X6 | P17096 | 1 | phosphorylation | down-regulates | 0.493 | Here, we found that hipk2 phosphorylates hmga1a at ser-35, thr-52, and thr-77, and hmga1b at thr-41 and thr-66. In addition, we demonstrated that cdc2, which is known to phosphorylate hmga1 proteins, could induce the phosphorylation of hmga1 proteins at the same ser/thr sites. we found that the hipk2-phosphorylated hmga1a reduced the binding affinity of hmga1a to human germ line promoter, and the drop in binding affinity induced by hipk2 phosphorylation was lower than that introduced by cdc2 phosphorylation. | SIGNOR-158620 |
Q13547 | P25490 | 1 | deacetylation | down-regulates activity | 0.798 | 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-268835 |
P05204 | P51812 | 0 | phosphorylation | down-regulates activity | 0.29 | We report here that the NBD of the HMGN1 and -N2 protein family is highly and specifically phosphorylated during mitosis and that this phosphorylation has a major functional consequence: it abolishes the interaction of the proteins with its chromatin targets. | SIGNOR-249102 |
O00238 | P43026 | 2 | binding | up-regulates activity | 0.774 | In contrast to other members of the TGF-beta superfamily, GDF-5 shows a pronounced specificity in type I receptor interaction in cross-link experiments binding only to BMP receptor IB (BMPR-IB). In mice, deletion of either GDF-5 or BMPR-IB results in a similar phenotype, indicating that GDF-5 signaling is highly dependent on BMPR-IB. | SIGNOR-256483 |
P04179 | Q9P275 | 0 | deubiquitination | up-regulates quantity by stabilization | 0.319 | Protein stability of mitochondrial superoxide dismutase SOD2 is regulated by USP36|Finally, USP36 was shown to be a specific deubiquitinating enzyme that reduces the ubiquitination level of SOD2 and was involved in SOD2 protein stability by extending its half-life. | SIGNOR-272280 |
Q9NY61 | P07288 | 1 | transcriptional regulation | up-regulates quantity by expression | 0.2 | Chromatin immunoprecipitation in combination with siRNA-mediated knockdown revealed that recruitment of AATF and ZIPK to the PSA enhancer was dependent on AR, whereas recruitment of TSG101 was dependent on AATF. | SIGNOR-253669 |
Q9BPV8 | P09471 | 2 | binding | up-regulates activity | 0.2 | 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-256749 |
P29353 | Q9UM73 | 0 | phosphorylation | up-regulates | 0.456 | Anaplastic lymphoma kinase (alk), which turned out to be one of these phosphoproteins, was constitutively activated and associated with the ptb domain of shcc in three neuroblastoma cells. In vitro kinase assay revealed that shcc is a potent substrate of the activated alk kinase. The alk gene locus was significantly amplified in both of these cell lines, suggesting that gene amplification leads to constitutive activation of the alk kinase, which results in hyperphosphorylation of shcc. | SIGNOR-91534 |
Q92570 | Q9BXH1 | 1 | transcriptional regulation | up-regulates quantity by expression | 0.2 | Over-expression of NR4A3 attenuated proliferation of cancer cells and promoted apoptosis by augmenting the expression of pro-apoptotic genes, PUMA and Bax. | SIGNOR-259396 |
O00566 | Q9NV31 | 2 | binding | up-regulates activity | 0.881 | Mpp10 represents a platform for the interaction of multiple factors within the 90S pre-ribosome. In eukaryotes, ribosome assembly is a highly complex process that involves more than 200 assembly factors that ensure the folding, modification and processing of the different rRNA species as well as the timely association of ribosomal proteins. One of these factors, Mpp10 associates with Imp3 and Imp4 to form a complex that is essential for the normal production of the 18S rRNA. | SIGNOR-261173 |
P19086 | O00398 | 2 | binding | up-regulates activity | 0.2 | 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-257121 |
P16298 | Q6VAB6 | 1 | dephosphorylation | up-regulates activity | 0.259 | These findings indicate that calcineurin modulates the phosphorylation state of KSR2, but not KSR1, and identifies S198, T287, and the S310 14-3-3 binding site as the KSR2 residues targeted by calcineurin.|the negative regulators 14-3-3 | SIGNOR-248381 |
Q99719 | O60260 | 0 | ubiquitination | down-regulates quantity | 0.2 | Furthermore, Parkin ubiquitinates and promotes the degradation of CDCrel-1.|Parkin functions as an E2-dependent ubiquitin- protein ligase and promotes the degradation of the synaptic vesicle-associated protein, CDCrel-1. | SIGNOR-278711 |
Q9HCE7 | Q9P2Y5 | 1 | ubiquitination | down-regulates activity | 0.2 | Here we report that UVRAG is ubiquitinated by SMURF1 at lysine residues 517 and 559, which decreases the association of UVRAG with RUBCN and promotes autophagosome maturation. However, the deubiquitinase ZRANB1 specifically cleaves SMURF1-induced K29 and K33-linked polyubiquitin chains from UVRAG, thereby increasing the binding of UVRAG to RUBCN and inhibiting autophagy flux. | SIGNOR-273652 |
O14640 | P63000 | 2 | binding | up-regulates activity | 0.584 | B-catenin-independent wnt signaling can activate rho family gtpases through at least two mechanisms: (1) direct activation of rac1 by dvl;and (2) activation of rhoa via dvl-associated activator of morphogenesis-1 (daam1), possibly through the weak-similarity guaninenucleotide exchange factor (wgef)1. | SIGNOR-185274 |
P08603 | P00751 | 2 | binding | down-regulates activity | 0.518 | As a regulator of the alternative pathway, FH binds to C3b and inhibits the binding of factor B to C3b, acts as a cofactor for the factor I-mediated cleavage of C3b to iC3b (cofactor activity), and accelerates the decay of C3bBb, the alternative pathway C3 convertase (decay-accelerating activity) | SIGNOR-252142 |
Q53EL6 | Q9UBS0 | 0 | phosphorylation | down-regulates | 0.438 | Both akt and p70(s6k) phosphorylate pdcd4, allowing for binding of the e3-ubiquitin ligase beta-trcp and consequently ubiquitylation. | SIGNOR-160992 |
Q9Y5I2 | Q9Y5F7 | 2 | binding | up-regulates activity | 0.2 | The clustered protocadherins comprise the largest subfamily of the cadherin superfamily and are predominantly expressed in the nervous system. Pcdh-alpha proteins interact with beta1-integrin to promote cell adhesion. They also form oligomers with Pcdh-gamma proteins at the same membrane sites. | SIGNOR-265715 |
Q15382 | Q14318 | 1 | gtpase-activating protein | down-regulates activity | 0.535 | Recent studies document that Rheb activates mTORC1 via direct, GTP-dependent interaction with the peptidyl-prolyl-cis/trans-isomerase FKBP38, which is proposed to act as an inhibitor of mTORC1. | SIGNOR-233568 |
Q9NPG1 | P56706 | 2 | binding | up-regulates | 0.647 | 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-131978 |
Q9UQM7 | Q14524 | 1 | phosphorylation | up-regulates activity | 0.398 | Among the sites identified, only six were previously suggested to be the targets for specific kinases using in silico and/or in vitro analyses: S36 and S525 were attributed to the regulation by PKA; S484 and S664 were assigned to the serum- and glucocorticoid-inducible kinase 3 (SGK3); and S516 and S571 were ascribed to CaMKII (reviewed in Marionneau and Abriel, 2015). In marked contrast, several previously described phosphorylation sites were not detected in the present study, including the PKA-dependent S528, the CaMKII-associated T594, the PKC-dependent S1506, the adenosine monophosphate–activated protein kinase (AMPK)–dependent T101 (Liu et al., 2019), and the six Fyn-dependent tyrosines (Ahern et al., 2005; Iqbal et al., 2018).|The simplest interpretation of these findings is that these three phosphorylation clusters, at positions S457-S460, S483-T486, and S664-S671, are likely involved in regulating the basal and/or gating properties of native cardiac NaV1.5 channels. Conversely, the other phosphorylation sites, with lower stoichiometries, may play spatially or temporally distinct roles in the physiological or more pathophysiological regulation of channel expression or gating. | Remarkably, this MS analysis also revealed that the vast majority of identified phosphorylation sites (at least 26) are clustered, suggesting concomitant phosphorylation and roles in regulating channel expression and/or function. Unexpectedly, however, except for S664, S667, and S671, no apparent effects of phosphomimetic or phosphosilent mutations were observed on heterologously expressed (in HEK-293 cells) NaV1.5 | SIGNOR-275772 |
Q16665 | P06493 | 0 | phosphorylation | up-regulates activity | 0.274 | In vitro kinase assays reveal that CDK1 directly phosphorylates HIF-1\u03b1 at a previously unidentified regulatory site, Ser668.|Overexpression of CDK1 and/or cyclin B1 is sufficient to stabilize HIF-1alpha under normoxic conditions, whereas inhibition of CDK1 enhances the proteasomal degradation of HIF-1alpha, reducing its half-life and steady-state levels. | SIGNOR-279599 |
P38405 | Q99705 | 2 | binding | up-regulates activity | 0.25 | 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-256905 |
Q69YH5 | P36873 | 2 | binding | up-regulates activity | 0.371 | This result demonstrates that the three sites of Repo-Man (Ser-543, Ser-977, and Ser-981) are phosphorylated by Aurora B in early mitosis. We uncover that PP1γ is recruited to mitotic chromosomes by its regulatory subunit Repo-Man in the absence of Aurora B activity and that Aurora B regulates dissociation of PP1γ by phosphorylating and disrupting PP1γ-Repo-Man interactions on chromatin. | SIGNOR-274003 |
O43603 | P08754 | 2 | binding | up-regulates activity | 0.45 | 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-256884 |
P31749 | P51812 | 1 | phosphorylation | down-regulates activity | 0.265 | Akt interacts with and phosphorylates RSK2 at S19. | SIGNOR-277548 |
P40763 | Q06124 | 0 | dephosphorylation | down-regulates activity | 0.77 | In addition, SHP-2 dephosphorylates tyrosine-phosphorylated Stat1/3/5A (Ohtani et al., 2000; Wu et al., 2002; Chen et al., 2003), and downregulates Stat3-mediated biological actions (Ohtani et al., 2000).|Inhibition of collagen-induced Stat3 tyrosine-705 (Stat3-p-Tyr) | SIGNOR-272404 |
P28482 | Q9NVD7 | 1 | phosphorylation | up-regulates activity | 0.259 | Actopaxin (alpha-parvin) is a paxillin, integrin-linked kinase, and F-actin binding focal adhesion protein with several serine phosphorylation sites in the amino terminus that contribute to the regulation of cell spreading and migration.|Actopaxin phosphorylation of Ser4/8 enhances cell migration whereas a nonphosphorylatable (Quint) mutant suppresses migration in U2OS osteosarcoma cells (7). | SIGNOR-265759 |
Q9UN86 | Q00987 | 2 | binding | down-regulates activity | 0.3 | G3BP2 binds to MDM2 and decreases its E3 ligase activity. The G3BP2 isoform additionally associated with murine double minute 2 (MDM2), a negative regulator of p53. G3BP2 expression resulted in significant reduction in MDM2-mediated p53 ubiquitylation and degradation. | SIGNOR-278892 |
P58400 | Q8N0W4 | 2 | binding | up-regulates activity | 0.77 | Pre- and postsynaptic plasma membranes are always precisely aligned, and are separated by a synaptic cleft of ~20 nm. The cleft contains an undefined proteinaceous material in the middle, and is presumably bridged by synaptic cell-adhesion molecules such as Nrxns and Nlgns that align the pre- and postsynaptic elements and mediate trans-synaptic signaling.|Nlgns bind to both alpha- and beta-Nrxns with nanomolar affinities; binding involves the sixth LNS-domain of alpha-Nrxns which corresponds to the only LNS-domain of beta-Nrxns52. The binding affinities differ characteristically between various pairs of Nlgns and Nrxns, and are controlled by alternative splicing of both Nrxns and Nlgns (Figure 1c) | SIGNOR-264150 |
O60296 | O60282 | 2 | binding | up-regulates activity | 0.549 | Trafficking kinesin proteins (TRAKs) are kinesin adaptors. They bind the cargo binding domain of kinesin-1 motor proteins forming a link between the motor and their cargoes. This supports the idea that the KIF5A–TRAK2 interaction is multivalent and could act to ensure stable motor-cargo interaction during intracellular trafficking; dimerization of both motor and adaptor molecules further enhances this stability (Fig. 6). A similar multivalent profile was found for the TRAK2 binding site within the kinesin-1 isoform, KIF5C. | SIGNOR-264064 |
O95644 | Q86V86 | 0 | phosphorylation | up-regulates activity | 0.246 | In addition to PIM1, also PIM2 and PIM3 were able to phosphorylate WT, but not MM NFATC1 in vitro (Fig. (Fig.22c). | SIGNOR-276773 |
Q92985 | O15111 | 0 | phosphorylation | up-regulates | 0.688 | Ikkalfa associated with and phosphorylated and activate interferon regulatory factor-7 (irf7), which is required for interferon-alfa (ifnalfa) production. | SIGNOR-146116 |
P51149 | O14818 | 2 | binding | up-regulates activity | 0.343 | Rab7 Forms a Complex with the Proteasome -Subunit XAPC. In this study the proteasome alpha-subunit XAPC7 (also known as PSMA7, RC6-1, and HSPC in mammals) was identified to interact specifically with Rab7 and was recruited to multivesicular late endosomes through this interaction. | SIGNOR-261303 |
Q9BXW4 | O95352 | 2 | binding | up-regulates activity | 0.789 | Lc3-i is activated by the same atg7 involved in atg12 conjugation, transferred to atg3, a second e2-like enzyme, and finally conjugated to pe | SIGNOR-191540 |
P06493 | Q9C0C7 | 1 | phosphorylation | up-regulates activity | 0.2 | CDK1 phosphorylates AMBRA1 at T1209 and S1223. |CDK1-mediated phosphorylation primes PLK1 phosphorylation on AMBRA1|In this work, we show that AMBRA1 is sequentially phosphorylated at mitosis by CDK1 and PLK1 on multiple sites. In particular, CDK1 is responsible for the early phosphorylations on T1209 and S1223, and it promotes additional late phosphorylation events by PLK1 on AMBRA1. Altogether, these phosphorylation events are critical for proper spindle function and orientation. Indeed, phosphorylated AMBRA1 can interact with NUMA1 and is responsible for NUMA1 proper localization at the cell cortex. Moreover, we observe that loss of AMBRA1 leads to PLK1 protein stabilization and to an increase in phospho-NUMA1 levels which, in turn, contributes to spindle orientation defects. | SIGNOR-272968 |
Q13200 | Q86V86 | 0 | phosphorylation | up-regulates activity | 0.2 | Seven of these kinases (PIM1/2/3, MAP4K1/2, PKA, and NEK6) directly and robustly phosphorylated recombinant GST-Rpn1 at S361 in vitro (Fig. 3D and SI Appendix, Fig. S3 A and B). | SIGNOR-273897 |
Q15418 | O14745 | 1 | phosphorylation | up-regulates activity | 0.33 | In summary, these results demonstrate that Ras-RSK1 signaling promotes nuclear localization of EBP50.|Specifically, RSK1 phosphorylates EBP50 at threonine 156 (T156) residue in a cell cycle dependent manner, which is important for nuclear translocation of EBP50 to facilitate cellular proliferation and transformation. | SIGNOR-278290 |
Q8IXH7 | P12931 | 0 | phosphorylation | down-regulates activity | 0.336 | Here we show that c-Src interacts with TH1 by GST-pull down assay, coimmunoprecipitation and confocal microscopy assay. The interaction leads to phosphorylation of TH1 at Tyr-6 in vivo and in vitro. Phosphorylation of TH1 decreases its association with A-Raf and PAK1. | SIGNOR-276402 |
P32121 | Q92835 | 2 | binding | up-regulates activity | 0.2 | We identified a new adaptor beta-arrestin 2 that associates with phosphorylated TIGIT and mediates recruitment of inositol phosphatase SHIP1 through the ITT-like motif (Fig. 7). Finally, SHIP1 impairs TRAF6 autoubiquitination to abolish NF-kappaB activation, leading to inhibition of IFN- gamma production in NK cells. | SIGNOR-261428 |
P45984 | P19793 | 1 | phosphorylation | down-regulates activity | 0.246 | Under stress conditions, hyperphosphorylated by activated jnk on ser-56, ser-70, thr-82 and ser-260. These findings indicate that inflammation-mediated cell signaling leads to rapid and profound reductions in nuclear rxralpha levels, via a multistep, jnk-dependent mechanism involving ser260, nuclear export, and proteasomal degradation. | SIGNOR-145301 |
Q9H4B4 | P30304 | 1 | phosphorylation | down-regulates | 0.383 | Here, we demonstrate that glycogen synthase kinase-3beta (gsk-3beta) phosphorylates cdc25a to promote its proteolysis in early cell-cycle phases. Phosphorylation by gsk-3beta requires priming of cdc25a, and this can be catalyzed by polo-like kinase 3 (plk-3) | SIGNOR-160228 |
Q14980 | Q9BUF5 | 2 | binding | up-regulates | 0.2 | Direct binding of numa to tubulin is mediated by a novel sequence motif in the tail domain that bundles and stabilizes microtubules. | SIGNOR-117109 |
Q13363 | P38398 | 1 | transcriptional regulation | down-regulates quantity by repression | 0.603 | Carboxyl-terminal binding protein 1 (CtBP1) is a transcriptional co-repressor with oncogenic potential. We found CtBP1 was recruited to the promoter regions of Brca1 and E-cadherin genes in breast cancer cells. | SIGNOR-259196 |
Q9Y2I7 | Q96BR1 | 0 | phosphorylation | up-regulates activity | 0.461 | The Western blot in XREF_FIG demonstrates that SGK3 as well as PKB phosphorylate PIKfyve at position S318, thereby indicating that PIKfyve could be a physiological target of SGK3.|We here identify a novel mechanism involving NMDA receptor triggered, SGK3 dependent stimulation of PIKfyve with subsequent formation of PI (3,5) P 2, which modulates RAB11A facilitated vesicle transport to the plasma membrane, leading to an increased abundance of GluA1 receptor subunits in the plasma membrane. | SIGNOR-279113 |
Q92466 | P00519 | 0 | phosphorylation | down-regulates | 0.458 | C-abl might act as a negative regulator of uv-ddb by phosphorylating ddb2 | SIGNOR-90446 |
P12931 | P31943 | 0 | post transcriptional regulation | up-regulates quantity by expression | 0.291 | HnRNP H is a component of a splicing enhancer complex that activates a c-src alternative exon in neuronal cells. | SIGNOR-261273 |
Q8NHM5 | Q99496 | 2 | binding | up-regulates activity | 0.609 | BcoR and Fbxl10/Jhdm1B are among the most abundant Ring1B/Rnf2 interactors identified with the highest confidence, and their association has been validated by coimmunoprecipitation studies; hence we call this the Fbxl10-BcoR complex. The assembly of Fbxl10-BcoR complex(es), the associations among its various subunits, and its functional significance remain to be characterized but are presently under investigation. | SIGNOR-252242 |
Q96EB6 | O43524 | 1 | deacetylation | up-regulates activity | 0.911 | Sirt1 increased foxo3's ability to induce cell cycle arrest and resistance to oxidative stress | SIGNOR-122405 |
P63092 | Q13639 | 2 | binding | up-regulates activity | 0.497 | 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 ‚â• -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 ‚â• -1.0 for defining true couplings. | The score associated to this interaction has a LogRAi ‚â• -1.0. | SIGNOR-256769 |
Q13705 | P84022 | 1 | phosphorylation | up-regulates activity | 0.69 | It has been suggested that binding of myostatin to the ActRIIB results in the phosphorylation of two serine residues of Smad2 or Smad3 at COOH domains | SIGNOR-254985 |
P41968 | Q96G30 | 2 | binding | down-regulates activity | 0.505 | We report that MRAP and MRAP2 can interact with all 5 MCRs. This interaction results in MC2R surface expression and signaling. In contrast, MRAP and MRAP2 can reduce MC1R, MC3R, MC4R, and MC5R responsiveness to [Nle4,D-Phe7]alpha-melanocyte-stimulating hormone (NDP-MSH). MRAP and MRAP2 can reduce the surface expression of MC4R and also the signaling of this receptor. we observed a significant decrease in the cell-surface expression of MC4R and MC5R in the presence of MRAP and MRAP2. It is interesting that MRAP and MRAP2 have opposite effects in the modulation of different MCR family members. | SIGNOR-252367 |
O60469 | Q9NP31 | 2 | binding | up-regulates activity | 0.2 | Our findings now further suggest that STAT3 and the adaptor protein SH2D2A interact with tyrosine‐containing motifs within the DSCAM/L1 ICDs. The SH2 domains of both STAT3 and SH2D2A are known to bind to phosphorylated tyrosine residues in the context of such motifs. Thus, the interactions between DSCAMs and SH2‐domain containing proteins seem to play a central and conserved role in Dscam signaling in the context of dynamic changes of tyrosine‐phosphorylation levels. | SIGNOR-264279 |
Q9NQ66 | P28482 | 0 | phosphorylation | up-regulates activity | 0.398 | coimmunoprecipitation detected a specific association between the activated erk and plc beta1 within the nucleus. In vitro studies revealed that recombinant plc beta1 could be efficiently phosphorylated by activated mitogen-activated protein kinase but not by pka. The erk phosphorylation site was mapped to serine 982 this result suggests that erk-evoked phosphorylation of plc beta1 at serine 982 plays a critical role in the activation of the nuclear pi cycle and is also crucial to the mitogenic action of igf-i. | SIGNOR-106561 |
P28482 | Q9UPT5 | 1 | phosphorylation | up-regulates | 0.331 | Erk1/2 phosphorylation enhances the binding of exo70 to other exocyst components and promotes the assembly of the exocyst complex in response to epidermal growth factor (egf) signaling. | SIGNOR-197543 |
Q9NXR1 | P06493 | 0 | phosphorylation | up-regulates activity | 0.654 | We found that Nudel and NudE were also phosphorylated in M phase (Fig. (Fig.22 and and3).3). First, Nudel and NudE were specifically phosphorylated in M phase. Moreover, both proteins were phosphorylated by Cdc2 and Erk2 in vitro.Due to conservation of the S/TP motifs, NudE may also be phosphorylated at similar sites by these kinases, though it contains an additional potential Cdk site at S282 (SPNR). | SIGNOR-274077 |
P46527 | Q15418 | 0 | phosphorylation | up-regulates activity | 0.393 | As for other PI3K effectors, RSK1 phosphorylates p27 at T198.|RSK1 overexpression increases p27pT198, p27-cyclin D1-Cdk4 complexes, and p27 stability. | SIGNOR-279653 |
P46934 | P27216 | 0 | relocalization | up-regulates quantity | 0.344 | Annexin XIII has two known isoforms, a and b, that are apically localized, although XIIIa is also found in the basolateral compartment. In vitro binding and coprecipitation experiments showed that the Nedd4-C2 domain interacts with both annexin XIIIa and b in the presence of Ca2+, and the interaction is direct and optimal at 1 μM Ca2+.These results suggest that the apical membrane localization of Nedd4 is mediated by an association of its C2 domain with the apically targeted annexin XIIIb. | SIGNOR-272571 |
Q13554 | P42224 | 1 | phosphorylation | up-regulates | 0.406 | 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-154771 |
Q14524 | Q96BR1 | 0 | phosphorylation | up-regulates activity | 0.275 | Among the sites identified, only six were previously suggested to be the targets for specific kinases using in silico and/or in vitro analyses: S36 and S525 were attributed to the regulation by PKA; S484 and S664 were assigned to the serum- and glucocorticoid-inducible kinase 3 (SGK3); and S516 and S571 were ascribed to CaMKII (reviewed in Marionneau and Abriel, 2015). In marked contrast, several previously described phosphorylation sites were not detected in the present study, including the PKA-dependent S528, the CaMKII-associated T594, the PKC-dependent S1506, the adenosine monophosphate–activated protein kinase (AMPK)–dependent T101 (Liu et al., 2019), and the six Fyn-dependent tyrosines (Ahern et al., 2005; Iqbal et al., 2018).|The simplest interpretation of these findings is that these three phosphorylation clusters, at positions S457-S460, S483-T486, and S664-S671, are likely involved in regulating the basal and/or gating properties of native cardiac NaV1.5 channels. Conversely, the other phosphorylation sites, with lower stoichiometries, may play spatially or temporally distinct roles in the physiological or more pathophysiological regulation of channel expression or gating. | Remarkably, this MS analysis also revealed that the vast majority of identified phosphorylation sites (at least 26) are clustered, suggesting concomitant phosphorylation and roles in regulating channel expression and/or function. Unexpectedly, however, except for S664, S667, and S671, no apparent effects of phosphomimetic or phosphosilent mutations were observed on heterologously expressed (in HEK-293 cells) NaV1.5 | SIGNOR-275767 |
Q13315 | Q16204 | 1 | phosphorylation | up-regulates | 0.274 | Phosphorylation of ccdc6 at thr434 by atm during dna damage response prevents fbxw7-mediated ccdc6 degradation. | SIGNOR-199276 |
P15923 | Q16539 | 0 | phosphorylation | up-regulates activity | 0.48 | Here we show that p38 mapk, whose activity is essential for myogenesis, regulates myod/e47 heterodimerization. Phosphorylation of e47 at ser140 by p38 induces myod/e47 association and activation of muscle-specific transcription | SIGNOR-134194 |
P34969 | P63096 | 2 | binding | up-regulates activity | 0.281 | 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-257055 |
Q9Y3Y4 | O00512 | 2 | binding | up-regulates | 0.907 | Here we report the identification of two segment polarity genes in drosophila, legless (lgs), and pygopus (pygo), and we show that their products are required for wnt signal transduction at the level of nuclear beta-catenin. Lgs encodes the homolog of human bcl9, and we provide genetic and molecular evidence that these proteins exert their function by physically linking pygo to beta-catenin. | SIGNOR-116577 |
Q13158 | O14733 | 0 | phosphorylation | down-regulates activity | 0.497 | The results clearly show that fadd phosphorylation at ser194 affects functions both upstream and downstream of the mekk1/mkk7/jnk1 pathway and is closely associated with chemosensitivity in prostate cancer cells | SIGNOR-123164 |
P27361 | P78536 | 1 | phosphorylation | up-regulates | 0.361 | Extracellular signal-regulated kinase phosphorylates tumor necrosis factor alpha-converting enzyme at threonine 735: a potential role in regulated sheddingwe show that extracellular signal-regulated kinase (erk) acts as an intermediate in protein kinase c-regulated trka cleavage. We report that the cytosolic tail of the tumor necrosis factor alpha-converting enzyme (tace) is phosphorylated by erk at threonine 735. In addition, we show that erk and tace associate. This association is favored by erk activation and by the presence of threonine 735. In contrast to the erk route, the p38 mapk was able to stimulate trka cleavage in cells devoid of tace activity, indicating that other proteases are also involved in trka shedding. | SIGNOR-89625 |
Q9GZQ8 | Q9NR19 | 0 | transcriptional regulation | up-regulates quantity by expression | 0.2 | As expected, we found that glucose deprivation induced the binding of TFEB (Figure S4C) and ACSS2 (Figure S4D) to the promoter regions of MAP1LC3B, ATG3, and WIPI-1 as well as mRNA (Figure 3H) and protein (Figure 3I) expression of these genes; | SIGNOR-276562 |
P05129 | O94768 | 1 | phosphorylation | down-regulates activity | 0.2 | These results suggest that phosphorylation of Ser350 plays an essential role in regulating translocation of DRAK2 to the nucleus from the cytoplasm, possibly by affecting the activity of the NLS. Ectopic expression of PKC-gamma induced cytoplasmic localization of DRAK2 and PKC-gamma phosphorylated Ser350 flanking the NLS. | SIGNOR-263178 |
Q8TB45 | P27361 | 0 | phosphorylation | up-regulates quantity by stabilization | 0.282 | Screening the DEPTOR interactome identified that the association of USP-7 deubiquitinase with DEPTOR was dependent upon S235 phosphorylation. Inhibition of USP-7 activity resulted in DEPTOR polyubiquitination and degradation. A scansite search suggested that ERK1 may be responsible for S235 phosphorylation, which was confirmed through the use of inhibitors, ERK1 knockdown, and an in vitro kinase assay. | SIGNOR-277587 |
P29597 | Q5VWK5 | 2 | binding | up-regulates | 0.582 | Il-23 activates the same jak-stat signaling molecules as il-12: jak2, tyk2, and stat1, -3, -4, and -5, but stat4 activation is substantially weaker and different dna-binding stat complexes form in response to il-23 compared with il-12. | SIGNOR-87841 |
P23771 | P23771 | 2 | null | up-regulates | 0.2 | Experimental data indeed supports the existence of a positive circuit involvingGATA-3 that excludes IL-4 and STAT-6, specifically in mouse cells | SIGNOR-254300 |
Q05655 | P11413 | 1 | phosphorylation | up-regulates | 0.2 | A pkc activator, significantly increased g6pd phosphorylation and activity, whereas single (s210a, t266a) and double (s210a/t266a) mutations at sites flanking the g6pd active site significantly inhibited phosphorylation, shifted the isoelectric point, and reduced enzyme activity. | SIGNOR-167053 |
Q9GZQ4 | P09471 | 2 | binding | up-regulates activity | 0.25 | 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-257010 |
Q9BZL6 | Q02156 | 0 | phosphorylation | up-regulates | 0.2 | In cells transfected with pkc? Or pkc? The phosphorylation of ser876 was markedly more pronounced than the phosphorylation of ser706/ser710 / the phosphorylation of ser706/ser710 in pkd2 reflects the activation of the kinase. | SIGNOR-89415 |
O95644 | P16298 | 0 | relocalization | up-regulates | 0.724 | The ca2+ dependent phosphatase calcineurin induces cardiac and skeletal muscle hypertrophy by a process that involves nf-at nuclear translocation, and activation of mef2c. | SIGNOR-84047 |
Q9UPQ9 | Q9UKV8 | 2 | binding | up-regulates activity | 0.796 | The assay showed that full-length TNRC6B binds full-length human AGO2. We have identified and molecularly dissected important sequence and structure features in the conserved Ago hooks of S. pombe Tas3 and human TNRC6B. The effect of Ago hook peptides from the shuttling P-body component TNRC6B in our miRNA-mediated translational repression assay (Fig. 5b), in particular, hints at a novel regulatory role of Ago hooks in miRNA-mediated gene repression mechanisms. | SIGNOR-269680 |
Q99683 | P31749 | 0 | phosphorylation | down-regulates activity | 0.729 | Akt phosphorylates and negatively regulates apoptosis signal-regulating kinase 1 akt decreased ask1 kinase activity stimulated by both oxidative stress and overexpression in 293 cells by phosphorylating a consensus akt site at serine 83 of ask1. | SIGNOR-252465 |
Q96DB2 | P25440 | 2 | binding | down-regulates activity | 0.339 | Ex vivo and cell-based assays revealed that HDAC11 catalytic activity suppresses the BAT transcriptional program, in both the basal state and in response to β-adrenergic receptor signaling, through a mechanism that is dependent on physical association with BRD2, a bromodomain and extraterminal (BET) acetyl-histone-binding protein. | SIGNOR-262058 |
P41229 | Q99814 | 0 | transcriptional regulation | up-regulates quantity by expression | 0.278 | To this end, we confirm that KDM3A, KDM4B, KDM4C, KDM5B, KDM5C, and KDM62 are direct targets of HIF-1a while extent the list of known targets to KDM2A, KDM2B, KDM4D, KDM5A, and KDM6A. The results demonstrated that majority of the KDMs were similarly induced (KDM2A, KDM2B, KDM3A, KDM4B, KDM4C, KDM4D, KDM5A, KDM5B, KDM5C, KDM6B, and KDM7A) or repressed (KDM NO66 and KDM1A) by both HIF-1a and HIF-2a. | SIGNOR-271579 |
P01106 | P24385 | 1 | transcriptional regulation | up-regulates quantity by expression | 0.496 | C-myc directly activates transcription of cyclin d1, cyclin d2 and cdk4, and leads to cdk 4/6 activation | SIGNOR-102731 |
P46527 | P49841 | 0 | phosphorylation | up-regulates quantity by stabilization | 0.389 | GSK-3\u03b2 phosphorylates p27 Kip1 at S160 and S161, resulting in increased p27 Kip1 stability [ xref ]. | SIGNOR-278938 |
Q12981 | Q96GF1 | 0 | polyubiquitination | up-regulates activity | 0.533 | RNF185 functions as a ubiquitin E3 ligase, enabling BNIP1-p62 interaction. Here we show that human RNF185 is a mitochondrial ubiquitin E3 ligase that regulates selective mitochondrial autophagy in cultured cells. Human BNIP1 colocalizes with RNF185 at mitochondria and is polyubiquitinated by RNF185 through K63-based ubiquitin linkage in vivo. The polyubiquitinated BNIP1 is capable of recruiting autophagy receptor p62, which simultaneously binds both ubiquitin and LC3 to link ubiquitination and autophagy. RNF185 interacts with BNIP1 and ATG5 | SIGNOR-271931 |
P02751 | P02679 | 2 | binding | down-regulates activity | 0.553 | Fibrinogen y-chain carboxyterminal (GQQHHLGGAKQAGDV) peptides inhibit fibrinogen, fibronectin (Fn), vitronectin, and von Willebrand factor (vWF) binding to the platelet glycoprotein Ilb-Illa complex (GP lIbII1a). | SIGNOR-251970 |
Q07812 | O43521 | 2 | binding | up-regulates activity | 0.832 | We have shown that the interaction of the bims and bimad isoforms with bax leads to a conformational change in this protein analogous to that triggered by the bh3-only protein bid.We find short peptides representing the alpha-helical bh3 domains of bid or bim are capable of inducing oligomerization of bak and bax to release cytochrome. | SIGNOR-87280 |
O75376 | P37231 | 1 | transcriptional regulation | down-regulates quantity by repression | 0.708 | In differentiated adipocyte cell lines, SIRT1 inhibits adipogenesis and enhances fat mobilization through lipolysis by suppressing the activity of PPARγ. SIRT1 achieves this by promoting the assembly of a corepressor complex, involving NCoR1 and SMRT, on the promoters of PPARγ target genes to repress their transcription. | SIGNOR-253507 |
P04234 | O60858 | 0 | polyubiquitination | down-regulates quantity by destabilization | 0.2 | RFP2, a gene frequently lost in various malignancies, encodes a protein with RING finger, B-box, and coiled-coil domains that belongs to the RBCC/TRIM family of proteins.Rfp2 Regulates the Stability of the ERAD Substrate CD3-δ. In summary, these experiments demonstrate that Rfp2 functions as a RING-dependent ERAD E3 ubiquitin ligase and regulates the degradation of the ER substrate, CD3-δ. | SIGNOR-271644 |
P49674 | Q6ZRV2 | 2 | binding | up-regulates quantity | 0.33 | We identified members of the FAM83 family of proteins as partners of CK1 in cells. All eight members of the FAM83 family (FAM83A–H) interacted with the α and α-like isoforms of CK1; FAM83A, -B, -E, and -H also interacted with the δ and ε isoforms of CK1. The intrinsic catalytic activity of CK1 is not affected by or required for the association of CK1 with FAM83 proteins. Our findings imply that the DUF1669 domains of FAM83 proteins anchor CK1 α, α-like, δ, and ε isoforms in specific subcellular compartments and potentially mediate their association with substrates. | SIGNOR-273764 |
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