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 |
|---|---|---|---|---|---|---|---|
O43614 | P08754 | 1 | binding | up-regulates activity | 0.264 | 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-256872 |
P49683 | Q14344 | 1 | binding | up-regulates activity | 0.264 | 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-257280 |
P17252 | P49768 | 1 | phosphorylation | up-regulates activity | 0.264 | A phosphorylation site at serine residue 346 was identified that is selectively phosphorylated by PKC but not by PKA. This site is localized within a recognition motif for caspases, and phosphorylation strongly inhibits proteolytic processing of PS1 by caspase activity during apoptosis. | SIGNOR-249236 |
P33981 | Q00987 | 1 | phosphorylation | up-regulates activity | 0.264 | (D and E) MDM2 was phosphorylated by hMps1 at Thr4, Thr306 and Ser307 in vitro.|In support, the MDM2 Ser307 to Ala mutant was less stable than the wild-type protein when coexpressed with hMps1 (Supplementary Figure S2B and C). hMps1 promotes MDM2-mediated H2B ubiquitination. (A) wild-type but not kinase-dead mutant hMps1 promotes MDM2-mediated H2B ubiquitination. 293T cells were transfected with the indicated plasmids and lysates were prepared for the Ni-NTA bead pulldown assay. 46999999="S307A"} | SIGNOR-279315 |
O60674 | Q9P0J1 | 1 | phosphorylation | down-regulates activity | 0.264 | Here we report that phosphorylation at another tyrosine residue, Tyr-94, inhibits PDP1 by reducing the binding ability of PDP1 to lipoic acid, which is covalently attached to the L2 domain of dihydrolipoyl acetyltransferase (E2) to recruit PDP1 to PDC. We found that multiple oncogenic tyrosine kinases directly phosphorylated PDP1 at Tyr-94, and Tyr-94 phosphorylation of PDP1 was common in diverse human cancer cells and primary leukemia cells from patients. | SIGNOR-276642 |
P35354 | P15172 | 1 | null | up-regulates | 0.264 | Furthermore, COX-2 inhibition reduced MyoD expression in regenerating muscle, suggesting a role for COX-2 in modulating muscle differentiation, as well as growth | SIGNOR-256214 |
Q05655 | P17096 | 1 | phosphorylation | down-regulates | 0.263 | In this study, we showed that the pkc-mediated phosphorylation of hmg-i exerted a very potent inhibition on the binding of this protein to the at-rich promoter regions of both pkc g and ng genes. The purified hmg-i can be phosphorylated by pkc a,b, g, and d but is poorly phosphorylated by pkc e and z. We have mapped two major sites of phosphorylation by pkc at ser44 and ser64 | SIGNOR-73610 |
P49840 | P52630 | 1 | phosphorylation | down-regulates quantity by destabilization | 0.263 | GSK3α/β are critical kinases to regulate STAT2 protein stability mediated by FBXW7.The 4-point mutant (STAT2-4A) of STAT2 at S381A/T385A/E389A/S393A inhibited GSK3α/β-mediated STAT2 phosphorylation. | SIGNOR-276761 |
P27361 | Q15648 | 1 | phosphorylation | up-regulates | 0.263 | Phosphorylation of transcriptional coactivator peroxisome proliferator-activated receptor (ppar)-binding protein (pbp). Stimulation of transcriptional regulation by mitogen-activated protein kinase | SIGNOR-93993 |
Q7Z6J0 | P15153 | 1 | binding | up-regulates | 0.263 | Posh interacts with the gtp form of rac but not the gdp form | SIGNOR-55811 |
Q96QT4 | P16885 | 1 | phosphorylation | up-regulates activity | 0.263 | We present data indicating that TRPM7 phosphorylates phospholipase C\u03b32 at position Ser1164 in the C2-domain, and at position Thr1045 in the linker between the catalytic region and the C2 domain. | SIGNOR-278460 |
Q86V86 | P61073 | 1 | phosphorylation | up-regulates quantity | 0.263 | Pim-1 and Pim-3 enhance phosphorylation and cell surface expression of CXCR4.|The intracellular tail of CXCR4 can be phosphorylated in vitro at Ser339 by Pim-1 kinase and by Pim-3, as shown here, but not by Pim-2. | SIGNOR-279092 |
Q9H1B7 | P01213 | 1 | transcriptional regulation | down-regulates quantity by repression | 0.263 | EAP1 encoded a nuclear protein expressed in neurons involved in the inhibitory and facilitatory control of reproduction. EAP1 transactivated genes required for reproductive function, such as GNRH1, and repressed inhibitory genes, such as preproenkephalin. It contained a RING finger domain of the C3HC4 subclass required for this dual transcriptional activity.These results suggest that EAP1 is a transcriptional regulator that, acting within the neuroendocrine brain, contributes to controlling female reproductive function. | SIGNOR-267156 |
O14920 | Q92934 | 1 | phosphorylation | down-regulates | 0.263 | Ikk phosphorylates bad at serine-26 (ser26) and primes it for inactivation. | SIGNOR-192614 |
Q9P278 | P08238 | 1 | binding | down-regulates activity | 0.263 | FNIP1 and FNIP2 facilitate FLCN binding to Hsp90 chaperone. Our results suggest that FNIP1 is a potent inhibitor of Hsp90 ATPase activity, as 200 nM of FNIP1 inhibits Hsp90 ATPase activity by 50-fold. FNIP2 also has shown inhibitory activity towards Hsp90; however, it required 1.6 μM of FNIP2 to inhibit the ATPase activity by eightfold. Although we use the term ‘inhibition' here, FNIPs seem only to be slowing the chaperone cycle. | SIGNOR-261416 |
P34995 | Q03113 | 1 | binding | up-regulates activity | 0.263 | 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-257278 |
Q9NUX5 | P35244 | 1 | binding | down-regulates activity | 0.263 | The current model for how telomeres repress ATR signaling proposes that POT1/TPP1 prevents the binding of RPA to the single-stranded telomeric DNA | SIGNOR-263326 |
P29274 | P08754 | 1 | binding | up-regulates activity | 0.263 | 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-257151 |
Q01484 | Q00975 | 1 | binding | up-regulates quantity | 0.263 | Here, we demonstrate that ankyrin-B associates with Cav2.1 and Cav2.2 in cortex, cerebellum, and brain stem. Additionally, using in vitro and in vivo techniques, we demonstrate that ankyrin-B, via its membrane-binding domain, associates with a highly conserved motif in the DII/III loop domain of Cav2.1 and Cav2.2. Collectively, our findings identify an interaction between ankyrin-B and both Cav2.1 and Cav2.2 at the amino acid level that is necessary for proper Cav2.1 and Cav2.2 targeting in vivo. | SIGNOR-266707 |
Q9BPZ7 | Q02156 | 1 | binding | up-regulates activity | 0.263 | In the present study, we have identified the mTORC2 subunit Sin1 as a direct binding partner of the PKC (protein kinase C) ε kinase domain and map the interaction to the central highly conserved region of Sin1. Exploiting the conformational dependence for PKC phosphorylation, we demonstrate that mTORC2 is essential for acute priming of PKC. | SIGNOR-276348 |
P42229 | Q06609 | 1 | transcriptional regulation | up-regulates quantity by expression | 0.263 | FLT3-ITD-TKD dual mutants induce hyperactivation of STAT5 and up-regulation of its downstream targets Bcl-x(L) and RAD51 in Ba/F3 cells | SIGNOR-261552 |
O15550 | P31270 | 1 | transcriptional regulation | up-regulates quantity by expression | 0.263 | Evidence for direct involvement of UTX in regulation of HOX gene activity was demonstrated through UTX knockdown experiments in HEK293T cells in which loss of UTX induced transcriptional repression of HOXA and HOXC clusters. | SIGNOR-260021 |
P23769 | P20396 | 1 | transcriptional regulation | up-regulates quantity by expression | 0.263 | The rat prepro-TRH gene is activated by GATA2. | SIGNOR-267259 |
Q16566 | P49841 | 1 | phosphorylation | down-regulates activity | 0.263 | CAMK4 phosphorylates GSK3\u03b2 at serine 9, which leads to its inactivation. xref Accordingly, we examined the levels of phosphorylated GSK3\u03b2 at serine 9 (pGSK3\u03b2-ser9) in podocytes exposed to IgG from TG patients and calculated the ratio of pGSK3\u03b2-ser9 to total GSK3\u03b2. | SIGNOR-279142 |
Q16584 | Q13526 | 1 | phosphorylation | up-regulates | 0.263 | Here we demonstrate that mixed-lineage kinase 3 (mlk3), a map3k family member, phosphorylates pin1 on a ser138 site to increase its catalytic activity and nuclear translocation. | SIGNOR-205586 |
P28482 | Q13625 | 1 | phosphorylation | up-regulates activity | 0.263 | Hence ASPP2 can be phosphorylated at serine 827 by MAPK1 in vitro.|Phosphorylation of ASPP2 by MAPK is required for RAS-induced increased binding to p53 and increased transactivation of pro-apoptotic genes. | SIGNOR-264414 |
Q01484 | O00555 | 1 | binding | up-regulates quantity | 0.263 | Here, we demonstrate that ankyrin-B associates with Cav2.1 and Cav2.2 in cortex, cerebellum, and brain stem. Additionally, using in vitro and in vivo techniques, we demonstrate that ankyrin-B, via its membrane-binding domain, associates with a highly conserved motif in the DII/III loop domain of Cav2.1 and Cav2.2. Collectively, our findings identify an interaction between ankyrin-B and both Cav2.1 and Cav2.2 at the amino acid level that is necessary for proper Cav2.1 and Cav2.2 targeting in vivo. | SIGNOR-266706 |
Q12899 | P78549 | 1 | ubiquitination | down-regulates quantity by destabilization | 0.263 | We also demonstrated that TRIM26 directly polyubiquitylates NTH1 in cells and that TRIM26 targets newly synthesized NTH1 protein for ubiquitylation dependent degradation. | SIGNOR-278733 |
Q14980 | P68363 | 1 | binding | up-regulates | 0.263 | Direct binding of numa to tubulin is mediated by a novel sequence motif in the tail domain that bundles and stabilizes microtubules. | SIGNOR-116472 |
P08047 | P28906 | 1 | transcriptional regulation | up-regulates quantity by expression | 0.263 | Activation of the CD34 promoter by Sp1 requires the presence of a binding domain at -48 bp as well as the 5' untranslated region, which also binds Sp1 | SIGNOR-241481 |
O14965 | P53667 | 2 | phosphorylation | up-regulates activity | 0.262 | Because Aur-A phosphorylates and activates LIMK1 , we examined the activation status of LIMK1 during mitosis in cells treated with MLN8237.|Because Aur-A phosphorylates and activates LIMK1 [ xref ], we examined the activation status of LIMK1 during mitosis in cells treated with MLN8237. | SIGNOR-279799 |
Q9HCE7 | Q5VWQ8 | 1 | ubiquitination | down-regulates quantity by destabilization | 0.262 | DAB2IP protein levels can be negatively regulated by the activity of the E3-ubiquitin ligases Fbw7, Skp2, and Smurf1 | SIGNOR-254776 |
P24588 | P48454 | 1 | relocalization | up-regulates activity | 0.262 | Using a viral-mediated molecular replacement strategy in rat hippocampal slices, we found that AKAP is required for NMDA receptor-dependent long-term depression solely because of its interaction with calcineurin | SIGNOR-261291 |
Q9H093 | Q9Y484 | 1 | phosphorylation | up-regulates activity | 0.262 | WIPI4 is stimulated by AMPK, NUAK2 and BRSK2. This finding is supported by the results of our kinome screening, which identified AMPK and the AMKP-related kinases NUAK2 and BRSK2, all of which function downstream of LKB1 (ref. 69) and stimulate the localization of WIPI4 to nascent autophagosomes. | SIGNOR-268481 |
P45983 | Q14451 | 1 | phosphorylation | down-regulates quantity by destabilization | 0.262 | Our data show that phosphorylation of Grb7 protein on the Ser194-Pro motif by c-Jun N-terminal kinase facilitates its binding with the WW domain of Pin1. Subsequently, Grb7 is degraded by the ubiquitin- and proteasome-dependent proteolytic pathway. I | SIGNOR-277280 |
P28482 | Q9H9Z2 | 1 | phosphorylation | down-regulates activity | 0.262 | Here we show that Lin28a is directly phosphorylated by ERK1/2 kinases at Ser-200. | SIGNOR-277338 |
P28827 | P40763 | 1 | dephosphorylation | down-regulates activity | 0.262 | Thus PTPRM suppresses STAT3 signaling in DDIAS-knockdown cells, suggesting that DDIAS promotes the IL-6\u2013mediated STAT3 signaling in malignant cancer cells by inhibiting the PTPRM function.|We report that PTPRM is a novel STAT3 tyrosine phosphatase and that it negatively regulates STAT3 activation by dephosphorylating Y705 of STAT3 in the presence of IL-6. | SIGNOR-277016 |
Q00535 | Q99490 | 1 | phosphorylation | up-regulates | 0.262 | Here, we demonstrate that cyclin dependent kinase 5 (cdk5), a protein known to function mainly in postmitotic neurons, directly phosphorylates pike-a at ser-279 in its gtpase domain in glioblastoma cells. This phosphorylation event stimulates pike-a gtpase activity and the activity of its downstream effector akt. | SIGNOR-178660 |
Q9NTX7 | O15234 | 1 | ubiquitination | down-regulates quantity by destabilization | 0.262 | Here, we identify RNF146, a RING-domain E3 ubiquitin ligase, as a positive regulator of Wnt signalling. RNF146 promotes Wnt signalling by mediating tankyrase-dependent degradation of axin. Mechanistically, RNF146 directly interacts with poly(ADP-ribose) through its WWE domain, and promotes degradation of PARsylated proteins. Using proteomics approaches, we have identified BLZF1 and CASC3 as further substrates targeted by tankyrase and RNF146 for degradation. | SIGNOR-263339 |
Q9UM11 | Q16875 | 1 | binding | down-regulates quantity by destabilization | 0.262 | We have recently discovered that the glycolysis-promoting enzyme 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase, isoform 3 (PFKFB3), is degraded by the E3 ubiquitin ligase APC/C-Cdh1, which also degrades cell-cycle proteins. Cdh1 promotes PFKFB3 degradation in the nucleus. | SIGNOR-271436 |
P15056 | P68104 | 1 | phosphorylation | down-regulates quantity by destabilization | 0.262 | Mass spectrometry identified in vitro S21 and T88 as phosphorylation sites mediated by B-Raf but not C-Raf on eEF1A1 whereas S21 was phosphorylated on eEF1A2 by both B- and C-Raf. | SIGNOR-276404 |
P12931 | P30411 | 1 | phosphorylation | up-regulates | 0.262 | Here we demonstrate that egf is capable of inducing src-mediated phosphorylation of the tyrosine residues 177 and 347 of bkr. Their replacement by phenylalanine led to bkr mutants which are unable to activate the camp pathway. | SIGNOR-141103 |
Q8IYW5 | P54132 | 1 | ubiquitination | up-regulates activity | 0.262 | Here, we demonstrate that the ubiquitin/SUMO-dependent DNA damage response (UbS-DDR), controlled by the E3 ligases RNF8/RNF168, triggers BLM recruitment to sites of replication fork stalling via ubiquitylation in the N-terminal region of BLM and subsequent BLM binding to the ubiquitin-interacting motifs of RAP80. | SIGNOR-272114 |
Q99835 | P19087 | 1 | binding | up-regulates | 0.262 | Consistent with its predicted topology, smo couples to a specific family of inhibitory g protein (gis) to regulate hh signaling. | SIGNOR-148534 |
Q99835 | P11488 | 1 | binding | up-regulates | 0.262 | Consistent with its predicted topology, smo couples to a specific family of inhibitory g protein (gis) to regulate hh signaling. | SIGNOR-148496 |
P53667 | O14965 | 2 | phosphorylation | up-regulates activity | 0.262 | Here, we report a novel functional cooperativity between Aur-A and LIMK1 through mutual phosphorylation. LIMK1 is recruited to the centrosomes during early prophase and then to the spindle poles, where it colocalizes with Aur-A. Aur-A physically associates with LIMK1 and activates it through phosphorylation, which is important for its centrosomal and spindle pole localization. Aur-A also acts as a substrate of LIMK1, and the function of LIMK1 is important for its specific localization and regulation of spindle morphology. | SIGNOR-276400 |
P19174 | P38936 | 1 | phosphorylation | up-regulates quantity by stabilization | 0.262 | Phosphorylation at Ser-146 by PKCδ increases p21 stability | SIGNOR-262962 |
P31749 | O60285 | 1 | phosphorylation | up-regulates | 0.262 | Ser(600) in ark5 was found to be phosphorylated by active akt resulting in the activation of kinase activity. | SIGNOR-252591 |
P58401 | Q14118 | 1 | binding | up-regulates activity | 0.262 | The DGC is potentially recruited to the postsynaptic membrane though a direct neurexin–dystroglycan interaction and an indirect interaction with NL2 via the synaptic scaffolding protein S-SCAM. | SIGNOR-265461 |
Q16539 | P49918 | 1 | phosphorylation | up-regulates | 0.262 | G1-s control by p38/hog1 sapks upon osmostress. Upon osmostress, activated p38 and hog1 sapks phosphorylate the s/cdk inhibitor p57 or sic1 respectively at one single residue. In mammalian cells (left panel), p57 phosphorylation on thr143 leads to an increase of the affinity of p57 towards the cyclin a/cdk2 complex leading to a g1 arrest. | SIGNOR-198390 |
Q9P2S2 | Q14118 | 1 | binding | up-regulates activity | 0.262 | The DGC is potentially recruited to the postsynaptic membrane though a direct neurexin–dystroglycan interaction and an indirect interaction with NL2 via the synaptic scaffolding protein S-SCAM. | SIGNOR-265460 |
P49674 | O75581 | 1 | phosphorylation | up-regulates | 0.262 | We find that ckiepsilon binds to lrp5 and lrp6 in vitro and in vivo and identify three ckiepsilon-specific phosphorylation sites in lrp6. Two of the identified phosphorylation sites, ser1420 and ser1430, influence wnt signaling in vivo, | SIGNOR-145049 |
P23470 | Q06187 | 1 | dephosphorylation | down-regulates activity | 0.262 | 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-254694 |
P53355 | P46821 | 1 | binding | up-regulates | 0.262 | Dapk-1 interacts with the microtubule-associated protein map1b, in particular in conditions of amino-acid starvation. | SIGNOR-181305 |
P21554 | O95837 | 1 | binding | up-regulates activity | 0.262 | 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-257211 |
Q9NR19 | P08236 | 1 | transcriptional regulation | up-regulates quantity by expression | 0.262 | Nucleus-Translocated ACSS2 Promotes Gene Transcription for Lysosomal Biogenesis and Autophagy|A chromatin immunoprecipitation (ChIP) assay with antibodies against TFEB or ACSS2 demonstrated that glucose deprivation results in the binding of TFEB (Figure 3D) and ACSS2 (Figure 3E) to the promoter regions of CTSA, GBA, GUSB, and LAMP1|These results indicated that TFEB and ACSS2 are mutually required for their binding to the promoter regions of lysosomal genes. In line with these findings, glucose deprivation induced mRNA (Figure 3F) and protein (Figure 3G) expression for these lysosomal genes, which was largely abrogated by knockin of ACSS2 mutants | SIGNOR-276554 |
Q96GD4 | Q9UKV0 | 1 | phosphorylation | down-regulates | 0.262 | We define the precise site of aurb-mediated phosphorylation as a conserved serine within the nuclear localization signals of hdac4, hdac5, and hdac9 at ser265, ser278, and ser242, respectivelyduring mitosis, aurb-mediated phosphorylation may localize class iia hdacs to a phosphorylation gradient at the spindle midzone, permitting temporal and spatial regulatory mechanisms altering hdac protein interactions | SIGNOR-198654 |
Q14774 | P18146 | 1 | transcriptional regulation | down-regulates quantity by repression | 0.262 | In this study, we have identified cell cycle regulatory genes as downstream targets of the homeobox gene HLX in cultured trophoblast cells, namely RB1, MYC, EGR1, CDKN1C, ELK1, CCNB1, and JUN. RB1 and MYC mRNA expression was increased with HLX inactivation, whereas EGR1, CDKN1C, ELK1, CCNB1, and JUN mRNA expression was decreased compared with mock-transfected control cells. | SIGNOR-261621 |
P17612 | P17655 | 1 | phosphorylation | down-regulates | 0.262 | Activation of m-calpain (calpain ii) by epidermal growth factor is limited by protein kinase a phosphorylation of m-calpain.These Data point to a novel mechanism of negative control of calpain activation, direct phosphorylation by pka. | SIGNOR-116248 |
Q5SQI0 | P68366 | 1 | acetylation | up-regulates quantity by stabilization | 0.262 | Alpha-Tubulin acetyltransferase (alphaTAT1) is the major α-tubulin lysine-40 (K40) acetyltransferase in mammals, nematodes, and protozoa, and its activity plays a conserved role in several microtubule-based processes.|The tubulin subunits of microtubules are acetylated, and lysine-40 (K40) of the alpha-tubulin subunit has been identified as an important conserved site of microtubule acetylation (6–8). This modification is considered a hallmark of stable, long-lived microtubules | SIGNOR-272249 |
Q9HCE7 | Q13243 | 1 | ubiquitination | down-regulates quantity by destabilization | 0.262 | K125 was also the major site of SRSF5 ubiquitylation mediated by Smurf1.|Smurf1 targets SRSF5 for degradation upon low glucose | SIGNOR-278665 |
P48454 | O00429 | 1 | dephosphorylation | up-regulates activity | 0.262 | When mitochondrial depolarization is associated with sustained cytosolic Ca(2+) rise, it activates the cytosolic phosphatase calcineurin that normally interacts with Drp1. Calcineurin-dependent dephosphorylation of Drp1, and in particular of its conserved serine 637, regulates its translocation to mitochondria as substantiated by site directed mutagenesis. | SIGNOR-248506 |
P31751 | Q13043 | 1 | phosphorylation | down-regulates | 0.262 | Full activation of mst1 requires an activation cleavage that is prevented by the phosphorylation of thr-387 by akt. | SIGNOR-201125 |
Q9Y5N1 | P09471 | 1 | binding | up-regulates activity | 0.261 | 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-256968 |
P06493 | O75170 | 1 | phosphorylation | down-regulates activity | 0.261 | We found that many interactions were abolished upon kinase inhibition; however, a subset was protected from phosphatase opposition or was unopposed, resulting in persistent interaction of the substrate with Plk1. This subset includes phosphoprotein phosphatase 6 (PP6), whose activity toward Aurora kinase A (Aurora A) was inhibited by Plk1. Our data suggest that this Plk1-PP6 interaction generates a feedback loop that coordinates and reinforces the activities of Plk1 and Aurora A during mitotic entry and is terminated by the degradation of Plk1 during mitotic exit. | SIGNOR-273587 |
Q96SB4 | Q9Y5S9 | 1 | phosphorylation | down-regulates | 0.261 | We demonstrate that y14 is phosphorylated at its repeated arginine/serine (rs) dipeptides, likely by sr protein-specific kinases. Phosphorylation of y14 abolished its interaction with ejc components as well as factors that function downstream of the ejc. | SIGNOR-139555 |
Q9NRW4 | P03372 | 1 | dephosphorylation | down-regulates activity | 0.261 | These results strongly suggest that DUSP22 acts as a negative regulator of the ERalpha-mediated signaling pathway|whereas E2-induced phosphorylation and activation of ERalpha was suppressed by overexpression of DUSP22 but not catalytically inactive mutants. | SIGNOR-248827 |
P49593 | Q13177 | 1 | dephosphorylation | down-regulates | 0.261 | Pop x2, a pp 2c serine/threonine phosphatase, is known to dephosphorylate pak and downregulate its activity. | SIGNOR-162149 |
Q05086 | P48436 | 1 | ubiquitination | down-regulates quantity by destabilization | 0.261 | We show that E6-AP ubiquitinates SOX9 in vitro and in vivo and that SOX9 levels are enhanced after addition of the proteasome inhibitor bortezomib. Similar, siRNA knockdown of E6-AP and the E2 ligase Ubc9 increased cellular SOX9 amounts, supporting the notion that SOX9 may be ubiquitinated in hypertrophic chondrocytes by E6-AP and degraded by proteasomes. | SIGNOR-272134 |
Q86Y01 | P50553 | 1 | binding | down-regulates | 0.261 | Through its binding to p300, dtx1 inhibited transcriptional activation by the neural-specific helix-loop-helix-type transcription factor mash1 | SIGNOR-110626 |
Q02750 | Q01538 | 1 | phosphorylation | down-regulates activity | 0.261 | Altogether our findings reveal that Myt1 is inactivated by MEK1 mediated phosphorylation to fragment the Golgi complex in G2 and for the entry of cells into mitosis.|MEK1 inactivates Myt1 to regulate Golgi membrane fragmentation and mitotic entry in mammalian cells. | SIGNOR-279052 |
P08047 | O43497 | 1 | transcriptional regulation | up-regulates quantity by expression | 0.261 | Consistent with this, Sp1 over-expression enhanced promoter activity while siRNA-mediated Sp1 silencing significantly decreased the level of CaV 3.1 protein and reduced the amplitude of whole-cell T-type Ca(2+) currents expressed in the N1E-115 cells. These results provide new insights into the molecular mechanisms that control CaV 3.1 channel expression. | SIGNOR-264034 |
Q9UKB1 | P84022 | 1 | ubiquitination | up-regulates | 0.261 | Here, we show that smad3 activated by tgf-beta is degraded by the ubiquitin-proteasome pathway. Smad3 interacts with a ring finger protein, roc1, through its c-terminal mh2 domain in a ligand-dependent manner. An e3 ubiquitin ligase complex roc1-scf(fbw1a) consisting of roc1, skp1, cullin1, and fbw1a (also termed betatrcp1) induces ubiquitination of smad3. | SIGNOR-108240 |
P20807 | Q15078 | 1 | cleavage | up-regulates activity | 0.261 | Calpains also modulate the activity of CDK5. Physiologically, CDK 5 is activated by p35 and its cleaved product p25. The latter has a longer half life than p35 and therefore it is a more potent activator of CDK5. The cleavage of p35 to p25 is mediated by calpain | SIGNOR-251604 |
Q9P1W9 | O95644 | 1 | phosphorylation | up-regulates activity | 0.261 | In addition to PIM1, also PIM2 and PIM3 were able to phosphorylate WT, but not MM NFATC1 in vitro (Fig. (Fig.22c). | SIGNOR-276772 |
O15530 | Q96PN8 | 1 | phosphorylation | up-regulates activity | 0.261 | We elucidated the mechanism of regulation of TSSK3 activity showing that autophosphorylation and PDK1 phosphorylation in the ‘activation loop’ are necessary for activation. | SIGNOR-260786 |
Q16665 | O94953 | 1 | transcriptional regulation | up-regulates quantity by expression | 0.261 | 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-271569 |
O00755 | P03956 | 1 | transcriptional regulation | up-regulates quantity by expression | 0.261 | Because MMP1 is also another direct target of the canonical Wnt pathway (22), Wnt7a overexpression upregulated MMP1/10 to degrade the extracellular matrix and to facilitate UBC cell invasion. | SIGNOR-278868 |
Q96PU5 | P35240 | 1 | ubiquitination | up-regulates activity | 0.261 | Merlin ubiquitination is mediated by the E3 ubiquitin ligase, NEDD4L, which requires a scaffold protein, AMOTL1, to approach Merlin. Several NF2-patient-derived Merlin mutations disrupt its binding to AMOTL1 and its regulation by the AMOTL1-NEDD4L apparatus. Lysine (K) 396 is the major ubiquitin conjugation residue. Disruption of Merlin ubiquitination by the K396R mutation or NEDD4L depletion diminishes its binding to Lats1 and inhibits Lats1 activation. These effects are also accompanied by loss of Merlin's anti-mitogenic and tumor suppressive properties. Thus, we propose that dephosphorylation and ubiquitination compose an intramolecular relay to activate Merlin functions in activating the Hippo pathway during growth control. | SIGNOR-263662 |
Q9Y243 | Q13043 | 1 | phosphorylation | down-regulates | 0.261 | Full activation of mst1 requires an activation cleavage that is prevented by the phosphorylation of thr-387 by akt. | SIGNOR-201129 |
Q02156 | Q96A00 | 1 | phosphorylation | up-regulates activity | 0.261 | A major kinase for GPCR‐induced CPI‐17 phosphorylation is PKC which is activated by the PLCbeta‐produced signaling messenger diacylglycerol (DAG). It phosphorylates CPI‐17 at Thr38 residue that directly docks at the active site of MLCP, thereby inhibiting its activity and promoting an increase of phosphorylation of myosin and of other MLCP. | SIGNOR-249258 |
P17252 | Q92793 | 1 | phosphorylation | down-regulates | 0.261 | The action of metformin was shown to be mediated through activation of apkc?/?, Which phosphorylates cbp at ser436, and disrupts the transcriptionally active creb-cbp-crtc2 complex, | SIGNOR-166368 |
Q12857 | A6NFN3 | 1 | transcriptional regulation | up-regulates quantity | 0.261 | For example, within the NFI targetome, we identified 6 collagen genes, 13 genes encoding potassium channel or glutamate receptor subunits and a range of factors related to axon guidance (e.g. Slit1, Robo1, Epha4, Epha5, Epha8) | SIGNOR-268911 |
Q8WZ73 | Q6MZQ0 | 1 | polyubiquitination | down-regulates quantity by destabilization | 0.261 | RFFL is an E3 ligase for PRR5L. | SIGNOR-271495 |
O96017 | Q9NQS7 | 1 | phosphorylation | up-regulates activity | 0.261 | Also, inhibition of Chk2 by Chk2 inhibitor II in cytokinesis after release of cells from a nocodazole-induced prometaphase block diminished INCENP localization to the midbody center in late midbodies (Fig. 1, M and N).|In turn, active Chk2 phosphorylates human INCENP at the newly identified site Ser91 to promote INCENP binding to Mklp2, resulting in recruitment of the INCENP\u2013Mklp2 complex to the midbody center through Mklp2\u2019s interaction with the midbody protein Cep55 to delay abscission. | SIGNOR-279695 |
P31751 | Q13188 | 1 | phosphorylation | down-regulates | 0.261 | Akt phosphorylates mst2 at thr117 in vitro and in vivo, which leads to mst2 cleavage and kinase activity as well as nuclear translocation. | SIGNOR-164302 |
Q12913 | P27986 | 1 | dephosphorylation | down-regulates | 0.261 | As reduction of pi3k activity by cd148 or shp-1 [32] is not large (2540%), it is likely that these ptps may function as modulators of the pi3k pathway rather than suppressors. | SIGNOR-178049 |
P31751 | Q04656 | 1 | phosphorylation | up-regulates quantity by stabilization | 0.261 | Akt2 (Protein Kinase B Beta) Stabilizes ATP7A, a Copper Transporter for Extracellular Superoxide Dismutase, in Vascular Smooth Muscle: Novel Mechanism to Limit Endothelial Dysfunction in Type 2 Diabetes Mellitus|Immunoprecipitation, in vitro kinase assay, and mass spectrometry analysis reveal that insulin stimulates Akt2 binding to ATP7A to induce phosphorylation at Ser1424/1463/1466 | SIGNOR-272268 |
Q15172 | P36897 | 1 | binding | up-regulates | 0.261 | In this report, we show that another wd-40 repeat protein, the balpha subunit of protein phosphatase 2a, associates with the cytoplasmic domain of type i tgf-beta receptors..[..] Furthermore, balpha enhances the growth inhibition activity of tgf-beta in a receptor-dependent manner | SIGNOR-60743 |
P49841 | Q9NR50 | 1 | binding | down-regulates | 0.261 | Akt also promotes protein synthesis by phosphorylating and inactivating gsk3b, thus releasing the gsk3b-dependent inhibition of the eukariotic translation initiation factor 2b (eif2b). | SIGNOR-175520 |
O14965 | Q9Y448 | 1 | phosphorylation | down-regulates activity | 0.261 | The protein astrin has been shown to remove Kif2b from kinetochores in metaphase through competitive binding of CLASP1 (Manning et al., 2010 blue right-pointing triangle). During prometaphase, Aurora B kinase activity prevents astrin from localizing to kinetochores (Manning et al., 2010 blue right-pointing triangle; Schmidt et al., 2010 blue right-pointing triangle). This permits Kif2b to localize to kinetochores to destabilize k-MT attachments to execute error correction through Plk1-dependent recruitment and activation. | SIGNOR-252052 |
P0DP24 | Q12756 | 1 | binding | up-regulates activity | 0.261 | To better understand how KIF1A-driven dense core vesicle (DCV) transport is regulated, we identified the KIF1A interactome and focused on three binding partners, the calcium binding protein calmodulin (CaM) and two synaptic scaffolding proteins: liprin-α and TANC2. We showed that calcium, acting via CaM, enhances KIF1A binding to DCVs and increases vesicle motility. In contrast, liprin-α and TANC2 are not part of the KIF1A-cargo complex but capture DCVs at dendritic spines | SIGNOR-266889 |
P12931 | O14744 | 1 | phosphorylation | down-regulates activity | 0.261 | Here, we demonstrate that PRMT5 is phosphorylated at residue Y324 by Src kinase, a negative regulator of its activity. | SIGNOR-277523 |
Q12923 | P06213 | 1 | dephosphorylation | down-regulates | 0.26 | We demonstrate that ptpl1, like ptp1b, interacts with and dephosphorylates a bis-phosphorylated insulin receptor peptide more efficiently than monophosphorylated peptides, indicating that ptpl1 may down-regulate the phosphatidylinositol 3-kinase pathway, by dephosphorylating insulin or growth factor receptors that contain tandem phosphotyrosines. | SIGNOR-132555 |
Q92915 | P35499 | 1 | binding | down-regulates activity | 0.26 | Sodium channel fast inactivation is modulated by alpha subunit interaction with a family of cytoplasmic proteins termed fibroblast growth factor homologous factors (FHFs). In this paper, we report that all A-type FHFs exert rapid onset long-term inactivation on Nav1.6 and other sodium channels. | SIGNOR-253433 |
Q96KB5 | Q06830 | 1 | phosphorylation | up-regulates | 0.26 | We report that prx1 is newly discovered direct target of topk. Our results demonstrate that topk phosphorylation of prx1 at ser-32 inhibits uvb-induced apoptosis in rpmi7951 melanoma cells by increasing prx1 peroxidase activity and decreasing the intracellular accumulation of h2o2. | SIGNOR-166901 |
P49841 | O75444 | 1 | phosphorylation | down-regulates | 0.26 | We showed that c-maf and mafb, like mafa, are indeed phosphorylated by gsk-3/ we demonstrated that phosphorylation by gsk-3 is conserved among the large maf proteins. It couples ubiquitination/degradation and transcriptional activation and modulates maf biological activity. | SIGNOR-159438 |
P00519 | O00429 | 1 | phosphorylation | up-regulates activity | 0.26 | In this study, we found that c-Abl phosphorylated Drp1 at tyrosine 266, 368 and 449 in vitro and in vivo, which augmented the GTPase activity of Drp1 and promoted Drp1-mediated mitochondrial fragmentation. | SIGNOR-277328 |
P12931 | Q13642 | 1 | phosphorylation | up-regulates activity | 0.26 | However, overexpression of Src promoted most of the Flag-FHL1-WT to translocate to the nucleus, whereas the Flag-FHL1-Y149-272F mutant (phosphorylation deficient mutant) remained in the cytoplasm (XREF_FIG).|We found that Src phosphorylates FHL1 at Y149 and Y272, demonstrating that FHL1 is a bona fide novel substrate of Src. | SIGNOR-278213 |
P23470 | P49023 | 1 | dephosphorylation | up-regulates activity | 0.26 | 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-254721 |
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