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 |
|---|---|---|---|---|---|---|---|
Q9UHD2 | Q14653 | 1 | phosphorylation | up-regulates activity | 0.822 | Virus-induced phosphoactivation of irf-3, thought to be mediated directly or indirectly by ikk? And/or tbk1 occurs in the c-terminal region of irf-3 at seven ser/thr residues, 385sslentvdlhisnshplslts405 (fig. 1a).Within This region, irf-3 has two phosphorylation sites: site 1 includes ser385 and ser386, whereas site 2 includes ser396, ser398, ser402, ser405, and thr404. | SIGNOR-178420 |
P51608 | O60524 | 2 | binding | up-regulates activity | 0.2 | MeCP2 interacts directly with Prpf3 and Sdccag1|MeCP2’s association with Prpf3, a major component of the spliceosome, supports MeCP2 as having a role in modulating mRNA splicing|Notably, Mecp2308/Y mice, which produce a truncated form of MeCP2 and reproduce many of the classical features of RTT [43], have been shown to have multiple genes that are abnormally spliced in the brain [23]. This suggests the C-terminal portion of MeCP2, which we have identified as the putative Sdccag1 interaction domain, plays a critical role in regulating alternative splicing. | SIGNOR-277692 |
P42336 | P09493 | 1 | phosphorylation | up-regulates activity | 0.2 | Here, we demonstrate a requirement for the protein kinase activity of PI(3)K in agonist-dependent beta-adrenergic receptor (betaAR) internalization. Using PI(3)K mutants with either protein or lipid phosphorylation activity, we identify the cytoskeletal protein non-muscle tropomyosin as a substrate of PI(3)K, which is phosphorylated in a wortmannin-sensitive manner on residue Ser 61. A constitutively dephosphorylated (S61A) tropomyosin mutant blocks agonist-dependent betaAR internalization, whereas a tropomyosin mutant that mimics constitutive phosphorylation (S61D) complements the PI(3)K mutant, with only lipid phosphorylation activity reversing the defective betaAR internalization. | SIGNOR-263027 |
O00429 | Q969V5 | 0 | sumoylation | up-regulates activity | 0.534 | Through a detailed analysis, we find that Drp1 interacts with the SUMO-conjugating enzyme Ubc9 via multiple regions and demonstrate that Drp1 is a direct target of SUMO modification by all three SUMO isoforms. | SIGNOR-274128 |
P60953 | Q9P2F6 | 0 | gtpase-activating protein | down-regulates activity | 0.447 | We therefore developed a screening-compatible live-cell imaging assay, using FRET-based biosensors for the prototype GTPases RHOA, RAC1 and CDC4215,19,20 (Extended Data Fig. 2 and Supplementary Note 1)|We found catalytic activities for 45/75 RhoGEFs and 48/63 RhoGAPs| Our data thus not only reveal extensive promiscuity among regulators, but also that the inactivating RhoGAPs are less selective than the activating RhoGEFs (p-value=0.02)(Supplementary Table 2). | SIGNOR-260474 |
P32245 | O95837 | 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-257392 |
P24941 | Q92698 | 1 | phosphorylation | down-regulates activity | 0.347 | Effect of CDK2 phosphorylation on the RAD54 activities. We find that the RAD54 N-terminal domain (NTD) is responsible for initiation of BM through two coupled, but distinct steps; specific binding to Holliday junctions and RAD54 oligomerization. Furthermore, we find that the RAD54 oligomeric state can be controlled by NTD phosphorylation at S49, a CDK2 consensus site, which inhibits RAD54 oligomerization and, consequently, BM. | SIGNOR-273599 |
P40259 | P07948 | 0 | phosphorylation | up-regulates activity | 0.678 | Y182 of CD79a appears to be the initial and preferred site of Ag receptor phosphorylation by Src family kinases. In vitro, Src family Lyn and Fyn predominantly phosphorylate this residue in CD79a, and Y195 does so in CD79b | SIGNOR-251398 |
P84022 | P17676 | 2 | 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 |
Q14527 | P12004 | 1 | ubiquitination | up-regulates activity | 0.78 | HLTF promotes the Lys-63-linked polyubiquitination of proliferating cell nuclear antigen (PCNA) that is required for maintaining genomic stability. | SIGNOR-278608 |
P48426 | P62330 | 0 | null | up-regulates activity | 0.338 | Effects of ARF6 upon Axonogenesis Are Mediated by Phosphatidyl-inositol-4-phosphate 5-Kinase α. activated ARF6 stimulates the lipid-modifying enzyme PI(4)P 5-Kinase, leading to local increases in plasma membrane PIP2 and changes in actin dynamics. Alternatively, activation of Rac1 by upstream Rac1 activators or indirectly by ARF6-GTP results in stimulation of actin polymerization. | SIGNOR-264911 |
P33176 | Q96N16 | 1 | relocalization | up-regulates activity | 0.2 | Marlin-1 is associated with kinesin-I and suggest that the movement of Marlin-1 is mediated by plus end microtubuledependent molecular motors | SIGNOR-260989 |
O14994 | P60709 | 2 | binding | up-regulates activity | 0.2 | Synapsins, a family of neuron-specific phosphoproteins, have been demonstrated to regulate the availability of synaptic vesicles for exocytosis by binding to both synaptic vesicles and the actin cytoskeleton in a phosphorylation-dependent manner. | SIGNOR-269183 |
P25490 | P12931 | 0 | phosphorylation | down-regulates activity | 0.284 | YY1 phosphorylation is mediated by Src family kinases. | SIGNOR-276940 |
P04637 | Q9H0M0 | 0 | ubiquitination | up-regulates activity | 0.319 | Unlike other E3 ligases, WWP1 increases p53 stability; inhibition of WWP1 expression or expression of a ligase-mutant form results in decreased p53 expression.|WWP1 associates with p53 and induces p53 ubiquitylation. | SIGNOR-278649 |
P40763 | O14543 | 1 | transcriptional regulation | up-regulates quantity by expression | 0.709 | We also found that the wild type SOCS-3 promoter construct has significantly greater activity in non-small-cell lung cancer cell lines than in normal cells in accordance with STAT3 disregulation in these cells | SIGNOR-253583 |
P16220 | P01189 | 1 | transcriptional regulation | up-regulates quantity by expression | 0.37 | Transcriptional activation of the proopiomelanocortin gene by cyclic AMP-responsive element binding protein|Further, expression of a dominant inhibitory mutant of CREB reduced cAMP stimulated transcription of the full length POMC promoter and the PTRE. | SIGNOR-268620 |
Q02952 | P06493 | 0 | phosphorylation | up-regulates activity | 0.322 | Mass spectrometry, molecular, and cellular approaches show that CDK1/Cyclin B1 phosphorylates Gravin on threonine 766 to prime the recruitment of the polo-like kinase Plk1 at defined phases of mitosis. | SIGNOR-271839 |
P61586 | O15068 | 0 | guanine nucleotide exchange factor | up-regulates activity | 0.619 | We therefore developed a screening-compatible live-cell imaging assay, using FRET-based biosensors for the prototype GTPases RHOA, RAC1 and CDC4215,19,20 (Extended Data Fig. 2 and Supplementary Note 1)|We found catalytic activities for 45/75 RhoGEFs and 48/63 RhoGAPs| Our data thus not only reveal extensive promiscuity among regulators, but also that the inactivating RhoGAPs are less selective than the activating RhoGEFs (p-value=0.02)(Supplementary Table 2). | SIGNOR-260559 |
P08047 | P06493 | 0 | phosphorylation | up-regulates | 0.463 | Moreover, we showed that sp1 is a novel mitotic substrate of cdk1/cyclin b1 and is phosphorylated by it at thr 739 before the onset of mitosis. | SIGNOR-163738 |
Q9H2X6 | Q15038 | 1 | phosphorylation | down-regulates activity | 0.2 | In response to DNA damage, HIPK2 phosphorylates DAZAP2 at several Ser/Thr residues including Ser77, which inhibits its HIPK2-degrading function and targets it to the cell nucleus. | SIGNOR-279335 |
P40763 | Q02156 | 0 | phosphorylation | up-regulates | 0.399 | Abrogation of pkcdelta activity inhibited insulin-induced stat3 phosphorylation, pkcdelta-stat3 association and nuclear translocation. | SIGNOR-143832 |
P42345 | Q13322 | 1 | phosphorylation | up-regulates | 0.412 | The adaptor protein grb10 was identified as an mtorc1 substrate that mediates the phosphoinositide 3-kinase. | SIGNOR-174071 |
Q9UGK3 | Q13882 | 0 | phosphorylation | up-regulates activity | 0.724 | Our previous studies revealed that STAP-2 binds to signal transducer and activator of transcription 3 (STAT3) and STAT5, and regulates the signaling pathways downstream of them. In the present study, we identified tyrosine-250 (Tyr250) in STAP-2 as a major site of phosphorylation by Brk, using a series of STAP-2 YF mutants and anti-phospho-STAP-2 Tyr250 antibody. Furthermore, overexpression of the STAP-2 Y250F mutant protein affected Brk-mediated STAT3 activation. | SIGNOR-247067 |
Q16816 | P10636 | 1 | phosphorylation | down-regulates activity | 0.313 | Muscle phosphorylase kinase phosphorylates Ser237, Ser262, Ser285, Ser305, and Ser352 of human tau. in vitro phosphorylation of tau on Ser262 alone strongly reduced the ability of tau to bind microtubules whereas the phosphorylation of many Ser/Thr-Pro motif sites of tau showed moderate effects on the binding of tau to microtubules | SIGNOR-250285 |
P07202 | P43699 | 0 | transcriptional regulation | up-regulates quantity by expression | 0.379 | TSH regulates TPO expression through the cAMP pathway and acts with thyroid-specific transcription factors such as TTF-1, TTF-2 and Pax-8. | SIGNOR-267278 |
P55085 | Q15661 | 2 | binding | up-regulates activity | 0.251 | Mast cells contribute to tissue repair in fibrous tissues by stimulating proliferation of fibroblasts through the release of tryptase which activates protease-activated receptor-2 (PAR-2).|Taken together, our data show that tryptase can stimulate myoblast proliferation and this effect is part of a signaling cascade dependent on PAR-2 activation and on the downstream activation of COX-2. | SIGNOR-251744 |
O14775 | Q08828 | 2 | binding | down-regulates activity | 0.456 | The D2-class dopamine receptors (D2, D3, and D4) couple to the Gi/o family of G proteins and thus induce inhibition of AC | SIGNOR-264996 |
P19086 | P25116 | 2 | binding | up-regulates activity | 0.447 | 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-257127 |
Q16539 | O15297 | 0 | dephosphorylation | down-regulates activity | 0.444 | Wip1 selectively inactivates p38 by specific dephosphorylation of its conserved threonine residue | SIGNOR-84793 |
P04180 | P02647 | 2 | binding | up-regulates activity | 0.782 | Activation of LCAT by apolipoprotein (apo) A-I on nascent (discoidal) high density lipoproteins (HDL) is essential for formation of mature (spheroidal) HDL during the antiatherogenic process of reverse cholesterol transport. After attachment of LCAT to discoidal HDL, the helix 5/5 domains in apoA-I form amphipathic presentation tunnels for migration of hydrophobic acyl chains and amphipathic UC from the bilayer to the phospholipase A2-like and esterification active sites of LCAT, respectively. | SIGNOR-252103 |
P23771 | Q15797 | 0 | transcriptional regulation | up-regulates quantity | 0.291 | 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-268938 |
Q9NZQ3 | P12931 | 0 | phosphorylation | up-regulates activity | 0.414 | These results indicate that phosphorylation of SPIN90 by Src is essential for its synaptic targeting. | SIGNOR-279387 |
P38435 | P22891 | 1 | carboxylation | up-regulates activity | 0.507 | Gamma-carboxylation is essential in the activation and proper functioning of multiple VK-dependent proteins (VKDP), the most well-known of which are involved in blood clotting, including coagulation factors (FII, FVII, FIX and FX) and natural anti-clotting agents (protein C, protein S (ProS; OMIM*176880) and protein Z | SIGNOR-265926 |
Q4VCS5 | Q9NRM7 | 0 | phosphorylation | up-regulates quantity by stabilization | 0.516 | Here low serum and high LATS1 activity are found to enhance the levels of the 130-kDa isoform of angiomotin (Amot130) through phosphorylation by LATS1/2 at serine 175, which then forms a binding site for 14-3-3. Such phosphorylation, in turn, enables the ubiquitin ligase atrophin-1 interacting protein (AIP)4 to bind, ubiquitinate, and stabilize Amot130 | SIGNOR-275846 |
Q07326 | Q5H8A4 | 2 | binding | up-regulates quantity by stabilization | 0.645 | We show that the human homolog of Gpi7p, termed hGPI7, binds to and is stabilized by PIG-F and that hGPI7 competes with PIG-O for binding to PIG-F. PIG-F Binds to and Stabilizes hGPI7 and PIG-O Independently. These results are consistent with the hypothesis that overexpression of hGPI7 decreases the biosynthetic activity of PIG-O by decreasing the available PIG-F, thereby destabilizing PIG-O. | SIGNOR-261358 |
P31947 | P45983 | 0 | phosphorylation | down-regulates | 0.338 | Jnk phosphorylates 14-3-3zeta_ at ser-184 and 14-3-3sigma_ at ser-187. | SIGNOR-124016 |
Q86TM6 | O15354 | 1 | polyubiquitination | down-regulates quantity by destabilization | 0.4 | We demonstrated that endogenous HRD1 interacts with Pael-R, and that HRD1 promotes the degradation of Pael-R and protects cell death caused by the accumulation of Pael-R. | SIGNOR-272631 |
P49841 | P13051 | 1 | phosphorylation | down-regulates quantity by destabilization | 0.2 | Here we show that glycogen synthase kinase 3 (GSK-3) interacts with and phosphorylates UNG2 at Thr60 and that Thr60 phosphorylation requires a Ser64 priming phosphorylation event.|phosphorylation of Thr60 and Ser64 creates a cyclin E/c-Myc-like phosphodegron that promotes polyubiquitylation and proteasome-mediated degradation | SIGNOR-264885 |
Q15022 | P53350 | 0 | phosphorylation | down-regulates quantity by destabilization | 0.362 | PLK1 and HOTAIR Accelerate Proteasomal Degradation of SUZ12 and ZNF198 during Hepatitis B Virus-Induced Liver Carcinogenesis|In SUZ12, residues 539, 541 and 546 phosphorylated by Plk1 in vitro | SIGNOR-275555 |
Q13315 | Q9UGP5 | 1 | phosphorylation | up-regulates activity | 0.354 | We show that Polλ is efficiently phosphorylated by DNA-PKcs in vitro and predominantly by ATM after DSB induction with ionizing radiation (IR) in vivo. We identify threonine 204 (T204) as a main target for ATM/DNA-PKcs phosphorylation on human Polλ, and establish that its phosphorylation may facilitate the repair of a subset of IR-induced DSBs and the efficient Polλ-mediated gap-filling during NHEJ. | SIGNOR-273836 |
P49841 | O00159 | 1 | phosphorylation | up-regulates activity | 0.2 | Here, we report that at early G1 the glycogen synthase kinase 3\u03b2 phosphorylates and stabilizes Nuclear myosin 1c, allowing for Nuclear myosin 1c association with the chromatin. | SIGNOR-279184 |
Q9BPZ7 | P23443 | 0 | phosphorylation | down-regulates activity | 0.565 | Consistently, we detected in vivo Sin1 phosphorylation triggered by S6K1 and to a lesser extent, Akt1, but not other characterized AGC kinases (XREF_FIG and XREF_SUPPLEMENTARY).|Here we report that phosphorylation of Sin1 at Thr 86 and Thr 398 suppresses mTORC2 kinase activity by dissociating Sin1 from mTORC2. | SIGNOR-279568 |
O75582 | P47712 | 1 | phosphorylation | up-regulates activity | 0.352 | Serine 727 phosphorylation and activation of cytosolic phospholipase A2 by MNK1-related protein kinases. | SIGNOR-249051 |
Q09472 | Q09472 | 2 | acetylation | up-regulates activity | 0.2 | Brd3 interacts with both IRF3 and p300, increases p300-mediated acetylation of IRF3, and enhances the association of IRF3 with p300 upon virus infection.|Brd3 enhances p300-mediated acetylation of IRF3|Importantly, Brd3 promotes the recruitment of IRF3/p300 complex to the promoter of Ifnb1, and increases the acetylation of histone3/histone4 within the Ifnb1 promoter, leading to the enhancement of type I interferon production. | SIGNOR-262045 |
Q9UQC2 | P06241 | 0 | phosphorylation | up-regulates activity | 0.605 | Our studies show that Gab2 is activated by Fyn kinase upon the engagement of ligand to TNFR1, IL-1R, or TLR4.|TNF\u03b1, IL-1\u03b2, and LPS induce Fyn kinase-mediated phosphorylation of Gab2. | SIGNOR-279984 |
P62166 | Q9NZN1 | 2 | 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 |
Q07912 | P10275 | 1 | phosphorylation | up-regulates activity | 0.545 | Ack1 interacted with and phosphorylated AR protein at Tyr 267 and Ack1 was shown to be required for optimal AR target gene expression and AR recruitment.|Two intracellular tyrosine kinases, Ack1 (activated cdc42 associated kinase) and Src, phosphorylate and enhance AR activity and promote prostate xenograft tumor growth in castrated animals. | SIGNOR-278194 |
P33981 | Q9Y5T5 | 1 | phosphorylation | down-regulates quantity by destabilization | 0.37 | Usp16 is a TTK phosphorylation substrate. | SIGNOR-277351 |
P99999 | Q9H3K2 | 0 | relocalization | down-regulates quantity | 0.255 | MICS1 was clearly coprecipitated with cytochrome c-3FLAG and the amount was DSP concentration-dependent (Figure 6A). Together with the finding that overexpression of exogenous MICS1 delayed the apoptotic release of cytochrome c in normal-serum level medium (Figure 4A), these results suggest that MICS1 helps to retain cytochrome c in the inner membrane, apart from the morphological changes. | SIGNOR-260294 |
P49841 | Q07812 | 1 | phosphorylation | up-regulates | 0.376 | Glycogen synthase kinase-3beta phosphorylates bax and promotes its mitochondrial localization during neuronal apoptosis. Gsk-3beta directly phosphorylated bax(alpha) on ser163 | SIGNOR-130141 |
P19438 | P28482 | 0 | phosphorylation | down-regulates activity | 0.5 | Phosphorylation of murine CD120a by p42(mapk/erk2) has been shown to inhibit its ability to initiate apoptosis while preserving signaling events such as NF-kappaB activation.|Additionally, we demonstrated that (i) the p42(mapk/erk2)-dependent phosphorylation of CD120a and DR3 occurred on Ser and Thr residues, (ii) p42(mapk/erk2) phosphorylated residues located in the membrane proximal regions but not the death domains of CD120a and DR3, (iii) Ser 253 is a preferred site of phosphorylation on CD120a | SIGNOR-249453 |
O14654 | P08069 | 0 | phosphorylation | up-regulates | 0.657 | Insulin-like growth factor i acting through its receptor was as effective as insulin in eliciting tyrosine phosphorylation of irs-4. | SIGNOR-56604 |
Q13118 | Q15582 | 1 | transcriptional regulation | up-regulates quantity by expression | 0.242 | Analyzing the mechanism of TGFBI up-regulation in clear cell carcinoma, we identified a novel VHL target, a Kruppel-like transcriptional factor 10 (KLF10). The TGFBI promoter, which we isolated and studied in Luc-reporter assay, was induced by KLF10 but not hypoxia. | SIGNOR-253212 |
Q9UEY8 | P17252 | 0 | phosphorylation | down-regulates quantity by destabilization | 0.334 | Results of in vitro experiments with recombinant alpha adducin demonstrated that PKC-phosphorylated adducin was proteolyzed by calpain more quickly than unphosphorylated adducin. | Phosphorylation of adducin by PKC may be a common mechanism for regulating adducin proteolysis by several proteases. | The antibody used in panel B is specific for the PKC-phosphorylated form of adducin. This antibody was raised against the phosphopeptide CKKFRTP[pS]FLKKNK, corresponding to amino acids 656-668 of human gamma adducin | SIGNOR-249143 |
Q96P48 | Q13882 | 0 | phosphorylation | up-regulates activity | 0.485 | ARAP1 associated with PTK6 in an EGF/EGF receptor (EGFR)-dependent manner. In addition, the SH2 domain of PTK6, particularly the Arg(105) residue that contacts the phosphate group of the tyrosine residue, was essential for the association. Moreover, PTK6 phosphorylated residue Tyr(231) in the N-terminal domain of ARAP1. Expression of ARAP1, but not of the Y231F mutant, inhibited the down-regulation of EGFR in HEK293 cells expressing PTK6. These results demonstrate that PTK6 enhances EGFR signaling by inhibition of EGFR down-regulation through phosphorylation of ARAP1 in breast cancer cells. | SIGNOR-263188 |
Q14790 | P28482 | 0 | phosphorylation | down-regulates | 0.757 | We demonstrate that perk 1/2 can phosphorylate pro-caspase-8 at s387 by knocking-down the endogenous pro-caspase-8 using rnai and replacing it with its non-phosphorylatable counterpart (s387a), a significant increase in caspase-8 activity | SIGNOR-203473 |
P53350 | Q9Y266 | 1 | phosphorylation | up-regulates activity | 0.73 | Here, we characterize the interaction between plk1 and nudc, show that plk1 phosphorylates nudc at conserved s274 and s326 residues in vitro, and present evidence that nudc is also a substrate for plk1 in vivo. Downregulation of nudc by rna interference results in multiple mitotic defects, including multinucleation and cells arrested at the midbody stage, which are rescued by ectopic expression of wild-type nudc, but not by nudc with mutations in the plk1 phosphorylation sites. | SIGNOR-103403 |
P55317 | O00712 | 2 | binding | up-regulates | 0.314 | Androgen receptor (ar) action throughout prostate development and in maintenance of the prostatic epithelium is partly controlled by interactions between ar and forkhead box (fox) transcription factors, particularly foxa1./ Foxa1 is capable of bringing ar and nfix into proximity, indicating that foxa1 facilitates the ar and nfi interaction by bridging the complex. | SIGNOR-205027 |
O15350 | Q9NYY3 | 0 | phosphorylation | down-regulates activity | 0.275 | PLK2 inhibits TAp73 translocation to the nucleus.|PLK2 phosphorylated TAp73 at residue Ser48 within the TA domain; phosphorylation of TAp73 was abolished by mutating this residue. | SIGNOR-278218 |
P25025 | P19876 | 2 | binding | up-regulates activity | 0.723 | CXCL2/3, also known as macrophage inflammatory protein-2α/2β (MIP-2α/MIP-2β), share the same receptor CXCR2 with CXCL1 and are able to activate neutrophils effectively | SIGNOR-277719 |
Q9UER7 | P25445 | 2 | binding | down-regulates | 0.703 | A c-terminal portion of daxx interacts with the fas death domain. The fas-binding domain of daxx is a dominant-negative inhibitor of both fas-induced apoptosis and jnk activation. | SIGNOR-49473 |
Q05397 | P51452 | 0 | dephosphorylation | down-regulates activity | 0.326 | Deficiency in VHR/DUSP3, a suppressor of focal adhesion kinase, reveals its role in regulating cell adhesion and migration.|In vitro assays proved that recombinant VHR directly dephosphorylated FAK and paxillin. | SIGNOR-277033 |
Q92626 | Q16236 | 0 | transcriptional regulation | up-regulates quantity by expression | 0.2 | PXDN expression in response to H2O2 and the Nrf2-specific inducers, tert-butylhydroquinone (tBHQ) and sulforaphane (SFN), was determined by western blotting and immunofluorescence microscopy, in HeLa and HEK293 cells.We found that Nrf2 binds to and increases luciferase reporter gene expression from the PXDN promoter via a putative Nrf2-binding site. In summary, we show that PXDN is a novel target of the redox sensitive transcription factor Nrf2. | SIGNOR-265248 |
P68400 | P09629 | 1 | phosphorylation | down-regulates activity | 0.344 | Thus, we concluded that CKII can phosphorylate HOXB7 in vitro and that this phosphorylation occurs at both of the CKII target sites, S133 and T204. | Wild-type HOXB7 inhibited the differentiation of 32D cells, whereas mutations in the Pbx-binding pentapeptide motif or the DNA-binding homeodomain, as well as internal deletions of the N-terminal unique region, blocked this effect. Interestingly, mutations eliminating two target sites for casein kinase II, the glutamate-rich C terminus, or the first 14 amino acids of HOXB7, led to enhanced 32D differentiation. | SIGNOR-250896 |
O95239 | Q96GD4 | 0 | phosphorylation | up-regulates activity | 0.517 | Using in vitro kinase assays, we found that active AMPK and Aurora B phosphorylated KIF4A at Ser801 and Thr799 respectively in a time-dependent manner (Figure 5D). KIF4A is phosphoregulated by AMPK and Aurora B. Although AMPK phosphorylation increased the ATPase activity of KIF4A, Aurora B phosphorylation resulted in a stronger increase (Figure 5I), which might be consistent with the more powerful kinase function of Aurora B during mitosis. | SIGNOR-265992 |
Q19QW5 | Q14974 | 1 | relocalization | down-regulates activity | 0.2 | ORF6 also retained KPNB1 at the ER/Golgi membrane in complex with KPNA2. Deletion of the N terminus of KPNA2, which binds KPNB1, no longer retained KPNB1 at the ER/Golgi membrane in the presence of ORF6 and did not antagonize STAT1 nuclear import in response to IFN-beta | SIGNOR-260275 |
Q9H0M0 | Q15583 | 2 | binding | up-regulates | 0.33 | We demonstrate that tiul1 degrades not only the activated type i receptor in association with smad7 but also smad2 in association with tgif.the steady-state levels of tgif are not affected by tiul1, but the interaction of tiul1 with tgif allows this ubiquitin ligase to target smad2 for degradation. | SIGNOR-128854 |
P17612 | O00141 | 1 | phosphorylation | up-regulates activity | 0.297 | In this publication, we demonstrate that cAMP can activate Sgk and that this effect is mediated by PKA, which directly phosphorylates Thr369 in Sgk. | SIGNOR-275972 |
Q04206 | Q99966 | 2 | binding | up-regulates | 0.2 | The transcriptional coactivator cpb/p300 associates with nf-kappa b p65 through two sites, an n-terminal domain that interacts with the c-terminal region of unphosphorylated p65, and a second domain that only interacts with p65 phosphorylated on serine 276. | SIGNOR-59054 |
P68400 | Q13428 | 1 | phosphorylation | up-regulates activity | 0.305 | Phosphorylated Thr 210 in Treacle is the major interaction site for NBS1|A purified GST fragment of this region was efficiently phosphorylated by CK2 in vitro (Supplementary Fig. 4; T-2) and this fragment pulled down the MRN complex from Hela nuclear extracts only when previously phosphorylated by CK2 | SIGNOR-265086 |
Q9HAU4 | Q13315 | 0 | phosphorylation | up-regulates activity | 0.2 | Using biochemical approaches and MS analysis, we show that upon the onset of the DNA-damage response, SMURF2 becomes phosphorylated at Ser384 by ataxia telangiectasia mutated (ATM) serine/threonine kinase, and this phosphorylation is required for its interaction with RNF20. | SIGNOR-277534 |
Q13972 | P17612 | 0 | phosphorylation | up-regulates | 0.519 | Phosphorylation of serine 916 of ras-grf1 contributes to the activation of exchange factor activity by muscarinic receptors. | SIGNOR-73202 |
P37198 | Q6UVJ0 | 2 | binding | up-regulates activity | 0.2 | Furthermore, we found interactions and co-localization with γ-tubulin and SAS-6. Our results also point to a potential role of Nup62 in targeting gamma-tubulin and SAS-6 to the centrioles. | SIGNOR-261256 |
Q16566 | Q8N5S9 | 0 | phosphorylation | up-regulates | 0.62 | Phosphorylation of ca(2+)/cam-bound camkiv on its activation loop threonine (residue thr(200) in human camkiv) by ca(2+)/calmodulin-dependent kinase kinase leads to increased camkiv kinase activity. | SIGNOR-134649 |
P55211 | Q9Y243 | 0 | phosphorylation | down-regulates | 0.518 | Akt phosphorylated recombinant casp9 in vitro on serine-196 and inhibited its protease activity | SIGNOR-61565 |
Q15303 | P22681 | 2 | binding | up-regulates | 0.572 | Erbb4 might not be able to directly recruit cbl, and therefore downregulation of this receptor is slow. | SIGNOR-147841 |
Q14249 | Q13490 | 0 | ubiquitination | up-regulates activity | 0.468 | Alternatively, cIAP1 may mediate a vital function of EndoG other than cell death.|Cellular inhibitor of apoptosis protein 1 ubiquitinates endonuclease G but does not affect endonuclease G-mediated cell death. | SIGNOR-278605 |
P13631 | P31749 | 0 | phosphorylation | up-regulates activity | 0.467 | S379 of RARγ is indispensable for the CLDN6-triggered cellular events. The most important finding of the present study is that the CLDN6/SFK/PI3K/AKT signaling controls the RARγ and ERα activities (Fig. 6). | SIGNOR-277492 |
P18846 | P68400 | 0 | phosphorylation | up-regulates | 0.296 | Camk ii phosphorylates only ser63 (corresponding to ser133 of creb), which is essential for the activation, and not ser72 (corresponding to ser142 of creb), which is a negative regulation site | SIGNOR-42565 |
Q8IYT8 | P42345 | 0 | phosphorylation | down-regulates | 0.777 | Mtor phosphorylates a mammalian homologue of atg13 and the mammalian atg1 homologues ulk1 and ulk2 | SIGNOR-183961 |
P53805 | Q13627 | 0 | phosphorylation | up-regulates | 0.562 | In the present study, dyrk1a is shown to directly interact with and phosphorylate rcan1 at ser112 and thr192 residues. Dyrk1a-mediated phosphorylation of rcan1 at ser112 primes the protein for the gsk3_-mediated phosphorylation of ser108. | SIGNOR-102290 |
P26022 | P08603 | 2 | binding | up-regulates activity | 0.398 | Our findings identify PTX3 as a unique FH ligand in that it can bind both of the two hot-spots of FH, namely SCR7 and SCR19-20 and indicate that PTX3 participates in the localization of functionally active FH. PTX3 binds FH without interfering with its complement inhibitory function. Therefore PTX3 may contribute to focusing FH regulatory action, prevent excessive complement activation, and thus exert an important function in the control of inflammation in response to tissue injury. | SIGNOR-252140 |
Q96Q89 | P06493 | 0 | phosphorylation | up-regulates activity | 0.41 | Here we report the identification of a novel KRP, termed KRMP1, which undergoes in vivo phosphorylation. The carboxyl-terminal globular tail domain is strongly phosphorylated by mitotic kinase activities almost attributed to cdc2 kinase, which is responsible for phosphorylation on residue Thr-1604 of KRMP1. | SIGNOR-262695 |
P84022 | P36896 | 0 | phosphorylation | up-regulates activity | 0.741 | ActRIIB, and then partners with a type I receptor, either activin receptor-like kinase 4 (ALK4 or ActRIB) or ALK5 (T²RI), to induce phosphorylation of Smad2/Smad3 and activate a TGF-²-like signaling pathway | SIGNOR-235160 |
P19525 | Q13283 | 2 | 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 |
P36406 | P37231 | 1 | ubiquitination | up-regulates quantity by stabilization | 0.2 | In this study, we showed that TRIM23 mediates atypical polyubiquitin conjugation including M1- and K27 linked ubiquitin chains to PPARgamma and that ubiquitination of PPARgamma by TRIM23 causes reduced recognition of PPARgamma by 26S proteasome. | SIGNOR-278577 |
Q03014 | Q01196 | 0 | transcriptional regulation | up-regulates quantity | 0.271 | We identified Hhex as a direct target of RUNX1 and FLT3-ITD stimulation and confirmed high HHEX expression in FLT3-ITD AMLs. HHEX could replace RUNX1 in cooperating with FLT3-ITD to induce AML. | SIGNOR-256305 |
P37840 | Q13627 | 0 | phosphorylation | up-regulates | 0.561 | In vitro kinase assay of anti-dyrk1a immunocomplexes demonstrated that dyrk1a could phosphorylate alpha-synuclein at ser-87. Furthermore, aggregates formed by phosphorylated alpha-synuclein have a distinct morphology and are more neurotoxic compared with aggregates composed of unmodified wild type alpha-synuclein. These findings suggest alpha-synuclein inclusion formation regulated by dyrk1a, potentially affecting neuronal cell viability. | SIGNOR-149393 |
P06493 | P04637 | 1 | phosphorylation | up-regulates activity | 0.579 | The N-terminus of E2F1 can interact directly with a region towards the C-terminus of p53, resulting in increased nuclear retention of p53 and p53-mediated transcription and apoptosis. This is inhibited by competition between p53 and cyclin A at the binding site within E2F19,10. The interaction between p53 and E2F1 is enhanced by phosphorylation of p53 on Ser315, a residue within the E2F1 binding region that is phosphorylated by cell cycle kinases such as cdk1, cdk2, cdk9 and Aurora kinase A | SIGNOR-167779 |
P17612 | P09874 | 1 | phosphorylation | up-regulates activity | 0.2 | In the presence of cAMP, recombinant PKA directly phosphorylated recombinant PARP1 on serines 465 (in the automodification domain) and 782 and 785 (both in the catalytic domain). | SIGNOR-276652 |
Q00839 | P01375 | 1 | post transcriptional regulation | up-regulates quantity by stabilization | 0.2 | In the present study, we show that hnRNP-U specifically enhances the expression of tumor necrosis factor alpha mRNA by increasing its stability, possibly through binding to the 3' untranslated region. We also show that hnRNP-U enhances the expression of several other genes as well, including GADD45A, HEXIM1, HOXA2, IER3, NHLH2, and ZFY, by binding to and stabilizing these mRNAs. | SIGNOR-262281 |
Q05513 | Q96RI1 | 1 | phosphorylation | up-regulates | 0.38 | The effect of fic1 on fxr phosphorylation and nuclear localization and its effects on bsep promoter activity could be blocked with protein kinase c zeta (pkc zeta) inhibitors (pseudosubstrate or small interfering rna silencing). Recombinant pkc zeta directly phosphorylated immunoprecipitated fxr. The mutation of threonine 442 of fxr to alanine yielded a dominant negative protein, | SIGNOR-179771 |
Q92963 | P55196 | 2 | binding | up-regulates activity | 0.2 | Rit and Rin were found to interact with the known Ras binding proteins RalGDS, Rlf, and AF-6/Canoe. These interactions were GTP and effector domain dependent and suggest that RalGDS, Rlf, and AF-6 are Rit and Rin effectors. | SIGNOR-220917 |
P53539 | P68400 | 0 | phosphorylation | up-regulates | 0.2 | Our findings indicate that ck2 activation increases deltafosb's transactivation potential, while ck2 inhibition decreases it. Further, we show that preventing ser27 phosphorylation by mutating the site to ala results in a significant decrease in deltafosb transactivation | SIGNOR-152403 |
P43146 | P12931 | 2 | binding | up-regulates activity | 0.535 | Here we show that different regions of the intracellular domain of DCC directly interacted with the tyrosine kinases Src and focal adhesion kinase (FAK). Netrin activated both FAK and Src and stimulated tyrosine phosphorylation of DCC. Inhibition of Src family kinases reduced DCC tyrosine phosphorylation and blocked both axon attraction and outgrowth of neurons in response to netrin. Mutation of the tyrosine phosphorylation residue in DCC abolished its function of mediating netrin-induced axon attraction. On the basis of our observations, we suggest a model in which DCC functions as a kinase-coupled receptor, and FAK and Src act immediately downstream of DCC in netrin signaling. | SIGNOR-268372 |
P47736 | P53350 | 0 | phosphorylation | down-regulates | 0.452 | Plk1 phosphorylates ser525 in conserved 524dsghvs529 degron of rap1gap and promotes its interaction with _-trcp. Together, these results further support a model in which plk1, but not cdk1 or gsk-3_-mediated phosphorylation of rap1gap is a prerequisite for mitotic degradation. | SIGNOR-205577 |
P78559 | Q13627 | 0 | phosphorylation | up-regulates activity | 0.2 | The phosphorylation of MAP1A and MAP2 by Dyrk1A was further confirmed by immunoprecipitating these proteins from the soluble fraction obtained after phosphorylating MTs (XREF_FIG). | SIGNOR-279032 |
Q96D31 | P05771 | 0 | phosphorylation | down-regulates | 0.2 | We propose that pkc suppresses soce and crac channel function by phosphorylation of orai1 at n-terminal serine residues ser-27 and ser-30. | SIGNOR-166040 |
Q14980 | Q71U36 | 2 | binding | up-regulates | 0.433 | Direct binding of numa to tubulin is mediated by a novel sequence motif in the tail domain that bundles and stabilizes microtubules. | SIGNOR-116640 |
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