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 |
|---|---|---|---|---|---|---|---|
P11309 | Q13309 | 1 | phosphorylation | up-regulates activity | 0.34 | We found that expression of Pim-1 increases the level of Skp2 through direct binding and phosphorylation of multiple sites on this protein. Along with known Skp2 phosphorylation sites including Ser(64) and Ser(72), we have identified Thr(417) as a unique Pim-1 phosphorylation target. Phosphorylation of Thr(417) controls the stability of Skp2 and its ability to degrade p27. | SIGNOR-259819 |
Q02363 | Q9Y574 | 0 | polyubiquitination | down-regulates quantity by destabilization | 0.341 | Using JAR placental cells, we determined that ASB4 ubiquitinates and represses ID2 expression in a proteasome-dependent fashion. | SIGNOR-272053 |
Q13950 | P49841 | 0 | phosphorylation | down-regulates activity | 0.301 | Collectively, these data demonstrate that the kinase activity of GSK-3beta suppresses the Runx2 transcriptional activity.|In vitro kinase assay confirmed that the Runx2 phosphorylation by GSK-3\u03b2 was reduced by the S369-S373-S377 mutation ( xref ). | SIGNOR-279051 |
P55211 | P31749 | 0 | phosphorylation | down-regulates activity | 0.775 | Akt phosphorylated recombinant casp9 in vitro on serine-196 and inhibited its protease activity | SIGNOR-252581 |
Q9NRX4 | O15554 | 1 | dephosphorylation | down-regulates activity | 0.549 | We now show that the mammalian protein histidine phosphatase (PHPT-1) directly binds and inhibits KCa3.1 by dephosphorylating histidine 358 on KCa3.1.|Overexpression of wild-type, but not a phosphatase dead, PHPT-1 inhibited KCa3.1 channel activity. | SIGNOR-277071 |
O14965 | Q8TEW0 | 1 | phosphorylation | up-regulates | 0.35 | Aurora a interacts directly with the atypical protein kinase c binding domain of par3 and phosphorylates it at serine 962. The phosphorylation of par3 at serine 962 contributes to its function in the establishment of neuronal polarity. | SIGNOR-188398 |
P35558 | P46379 | 0 | acetylation | down-regulates quantity by destabilization | 0.34 | These results indicate that BAT3 and P300 can both exist in the PEPCK1 protein complex, suggesting the possibility that BAT3 could be an enhancer of PEPCK1 acetylation. | indicating a synergistic effect of BAT3 and P300 to promote PEPCK1 acetylation. | SIGNOR-267598 |
Q6ZWJ1 | P46937 | 2 | binding | down-regulates activity | 0.2 | WW domain‐containing protein STXBP4 inhibits YAP activity via LATS1‐mediated phosphorylation. | SIGNOR-260013 |
P00519 | P15172 | 1 | phosphorylation | down-regulates activity | 0.286 | We have found that c-Abl can phosphorylate MyoD at a conserved N-terminal tyrosine (Tyr30) that is located within the transactivation domain. Mutation of Tyr30 to Phe does not interfere with the function of MyoD, but theTyr30Phe mutant becomes resistant to the inhibitory effect of DNA damage. | SIGNOR-253055 |
P63104 | P48729 | 0 | phosphorylation | down-regulates activity | 0.579 | This protein kinase has been identified as casein kinase Ialpha (CKIalpha) by peptide mapping analysis and sequencing. Among mammalian 14-3-3, only 14-3-3 tau possesses a phosphorylatable residue at the same position (Ser-233), and we show that this residue is also phosphorylated by CKI. In addition, we show that 14-3-3 zeta is exclusively phosphorylated on Thr-233 in human embryonic kidney 293 cells. The residue 233 is located within a region shown to be important for the association of 14-3-3 to target proteins. | We have now shown that in vivo phosphorylation of 14-3-3 zeta at the CKIalpha site (Thr-233) negatively regulates its binding to c-Raf, and may be important in Raf-mediated signal transduction. | SIGNOR-250796 |
Q12824 | Q96EP1 | 0 | polyubiquitination | down-regulates quantity by destabilization | 0.316 | Here we report that CHFR interacts with BRG1, SNF5, and BAF60a of the SWI/SNF-like BAF complex and ubiquitinates them to target for degradation through a proteasome-mediated pathway, and that SRG3/mBAF155 stabilizes these components by blocking their interaction with CHFR. These results suggest that CHFR enhances the degradation of the components of the SWI/SNF-like BAF complex by inducing their poly-ubiquitination. | SIGNOR-271458 |
P84243 | Q9BY66 | 0 | demethylation | up-regulates activity | 0.2 | KDM5 subfamily is capable of removing tri‐ and di‐ methyl marks from lysine 4 on histone H3 (H3K4). Depending on the methylation site, its effect on transcription can be either activating or repressing. | SIGNOR-264310 |
P06213 | Q13322 | 2 | binding | down-regulates | 0.66 | Grb10 negatively regulates growth factor signaling. It binds the insulin and insulin-like growth factor 1 (igf-1) receptors;mice without grb10 are larger and exhibit enhanced insulin sensitivity. | SIGNOR-174065 |
Q9NPG1 | Q9H1J7 | 2 | binding | up-regulates | 0.636 | Human wnt5a, wnt5b and wnt11 are non-canonical wnt ligands transducing pcp signals through fzd3 or fzd6 receptors. | SIGNOR-141440 |
Q00987 | Q9UER7 | 2 | binding | up-regulates | 0.673 | The optimal function of mdm2 requires daxx, which stabilizes mdm2 through the deubiquitinase hausp/usp7 and also directly promotes mdm2's ubiquitin ligase activity towards p53. | SIGNOR-200892 |
P53350 | P62826 | 1 | phosphorylation | up-regulates | 0.264 | Plk1 is capable of phosphorylating co-immunoprecipitated ran in vitro on serine-135 and ran is phosphorylated in vivo at the same site during mitosis when plk1 is normally activated. Deregulation of ran phosphorylation disrupts normal spindle structure and segregation of chromosomes. | SIGNOR-149073 |
Q9UKT4 | Q9UM11 | 1 | ubiquitination | down-regulates | 0.756 | Emi1 binds cdh1 and inhibits apc-cdh1 activity. | SIGNOR-113385 |
Q15561 | Q9GZV5 | 2 | binding | up-regulates | 0.869 | When dephosphorylated, yap/taz enter nuclei and induce gene transcription by interacting with transcription factors tead14. | SIGNOR-201459 |
Q16665 | Q96A26 | 1 | transcriptional regulation | up-regulates quantity by expression | 0.282 | In this work, we report the identification of an HIF-1 alpha-responsive proapoptotic molecule, HGTD-P. Its expression was directly regulated by HIF-1 alpha through a hypoxia-responsive element on the HGTD-P promoter region. | SIGNOR-260292 |
P24844 | Q05397 | 0 | phosphorylation | up-regulates activity | 0.286 | It indicates that FAK positively regulates the phosphorylation of MLC2. | SIGNOR-280098 |
O43318 | Q13546 | 2 | binding | up-regulates activity | 0.553 | RIP-1 recruitment of MEKK-3 and transforming growth factor-beta (TGFbeta)-activated kinase (TAK1) subsequently activates the IKK (inhibitor of κB kinase) complex | SIGNOR-256022 |
P30305 | Q14680 | 0 | phosphorylation | down-regulates activity | 0.533 | In the present study we show that the human pEg3 kinase is able to specifically phosphorylate CDC25B in vitro. One phosphorylation site was identified and corresponded to serine 323[Ä] Taken together these results suggest that pEg3 is a potential regulator of the G2/M progression and may act antagonistically to the CDC25B phosphatase | SIGNOR-255655 |
Q16236 | P22830 | 1 | transcriptional regulation | up-regulates quantity by expression | 0.322 | NFE2L2 is stabilized and translocates to the nucleus, where it dimerizes with sMAF proteins. This complex binds to AREs to mediate the transcription of genes involved in iron metabolism, GSH metabolism, and ROS detoxification.Two critical enzymes in this pathway, ATP binding cassette subfamily B member 6 (ABCB6) and ferrochelatase (FECH), are regulated by the transcription factor NFE2L2 and play significant roles in inhibiting ferroptosis when upregulated. | SIGNOR-279865 |
Q8WU17 | Q9Y5U4 | 1 | ubiquitination | down-regulates quantity | 0.436 | Induction of TRC8 destabilized the precursor forms of the transcription factors SREBP-1 and SREBP-2. TRC8 destablizes SREBP precursors in a RING and proteasome-dependent manner | SIGNOR-271956 |
O14965 | P41208 | 1 | phosphorylation | up-regulates | 0.516 | Our studies show that aurora a phosphorylates centrin at serine 170 in vitro and that the serine 170 phosphorylation affects the stability of centrin by regulating its interaction with apc/c. finally we demonstrated that phosphorylation of centrin serine 170 is an absolute requirement for aurora a-mediated centriole amplification. | SIGNOR-174686 |
P09874 | P42574 | 0 | cleavage | down-regulates activity | 0.775 | Caspase-3 cleaves parp-1. During cd95-mediated apoptosis proteolytic inactivation of parp-1 by caspases prevents atp depletion and thereby ensures the execution of the apoptotic process | SIGNOR-116178 |
P51149 | Q96Q42 | 2 | binding | down-regulates activity | 0.305 | The absence of active Rab7 prolongs ALS2presence and Rab5 activation on macropinosomes, indicating that activeRab7 is necessary for Rab5 inactivation through ALS2 dissociation and playskey roles in the Rab switch on macropinosomes. Taken together, active Rab7is necessary for Rab5 down-regulation through ALS2dissociation, thereby acting as a central component inthe Rab5-to-Rab7 switch in macropinocytosis | SIGNOR-277778 |
Q00987 | P62136 | 0 | dephosphorylation | up-regulates quantity by stabilization | 0.356 | Three phosphorylation sites identified are Ser342, Ser367, and Ser403. In the present study, we identify protein phosphatase 1 (PP1) as a negative regulator in the p53 signaling pathway. PP1 directly interacts with Mdmx and specifically dephosphorylates Mdmx at Ser367. The dephosphorylation of Mdmx increases its stability and thereby inhibits p53 activity. | SIGNOR-248566 |
Q14653 | P0C6X7-PRO_0000037311 | 0 | deubiquitination | down-regulates activity | 0.2 | Here we show that PLpro also inhibits IRF3 activation at a step after phosphorylation and that this inhibition is dependent on the de-ubiquitination (DUB) activity of PLpro. We found that PLpro is able to block the type I IFN induction of a constitutively active IRF3, but does not inhibit IRF3 dimerization, nuclear localization or DNA binding. However, inhibition of PLpro’s DUB activity by mutagenesis blocked the IRF3 inhibition activity of PLpro, suggesting a role for IRF3 ubiquitination in induction of a type I IFN innate immune response. | SIGNOR-260249 |
P01009 | Q12907 | 2 | binding | up-regulates quantity by stabilization | 0.434 | Identification of α1‐antitrypsin as interaction partner of VIP36. The complex formed by VIP36 and alpha1-AT in the Golgi recycled back to the ER. The combined data are most consistent with a function of VIP36 in post-ER quality control of alpha1-AT. We propose that VIP36 acts in post‐ER quality control in the Golgi by binding incompletely folded α1‐AT, which inadvertently escaped ER quality control, and by recycling it back to the ER for an additional round of quality control. | SIGNOR-261356 |
P23769 | P06493 | 0 | phosphorylation | down-regulates quantity by destabilization | 0.355 | GATA2 contains a cell division control protein 4 (Cdc4) phosphodegron (CPD), a consensus motif for ubiquitylation by Fbw7, which includes Thr(176). Ectopic expression of Fbw7 destabilized GATA2 and promoted its proteasomal degradation. Substitution of threonine 176 to alanine in GATA2 inhibited binding with Fbw7, and the ubiquitylation and degradation of GATA2 by Fbw7 was suppressed. The CPD kinase, which mediates the phosphorylation of Thr(176), was cyclin B-cyclin-dependent kinase 1 (CDK1). | SIGNOR-276884 |
P50613 | P19447 | 1 | phosphorylation | down-regulates quantity by destabilization | 0.895 | These results led us to propose a model that spironolactone may trigger the phosphorylation of XPB at Ser90 by CDK7, which promotes the recognition and polyubiquitination of XPB by SCFFBXL18 for proteasomal degradation. | SIGNOR-277433 |
P98177 | P45983 | 0 | phosphorylation | up-regulates | 0.612 | Upon treatment of cells with h2o2, the small gtpase ral is activated and this results in a jnk-dependent phosphorylation of foxo4 on threonine 447 and threonine 451. This ral-mediated, jnk-dependent phosphorylation is involved in the nuclear translocation and transcriptional activation of foxo4 after h2o2 treatment. | SIGNOR-130385 |
P51608 | Q8NFU7 | 2 | binding | up-regulates activity | 0.428 | MeCP2 and its partners, splicing factor Y-box binding protein 1 (YB-1) and methylcytosine dioxygenase 1 (Tet1), bind to BDNF chromatin in naı ̈ve but dissociate during conditioning|Knockdown of MeCP2 shows it is instrumental for splicing and inhibits Tet1 and CTCF binding thereby negatively impacting DNA methylation and conditioning-dependent splicing regulation. Thus, mutations in MECP2 can have secondary effects on DNA methylation and alternative splicing. | SIGNOR-277701 |
Q9Y2X7 | Q02750 | 2 | binding | up-regulates activity | 0.391 | We found both MAT2B variants interact with GIT1. MAT2B directly promoted binding of GIT1 and ERK2 to MEK1. MAT2B and GIT1 interact and are overexpressed in most human liver and colon cancer specimens. | SIGNOR-261245 |
Q9NP71 | Q13085 | 1 | transcriptional regulation | up-regulates quantity by expression | 0.435 | The present study provides evidence for a direct and dominant role of ChREBP in the glucose regulation of two key liver lipogenic enzymes, acetyl-CoA carboxylase (ACC) and fatty acid synthase (FAS) | SIGNOR-267946 |
P49715 | Q15466 | 2 | binding | down-regulates activity | 0.269 | SHP repressed C/EBPalpha (CCAAT/enhancer-binding protein alpha)-driven transcription of PEPCK through direct interaction with C/EBPalpha protein both in vitro and in vivo. The formation of an active transcriptional complex of C/EBPalpha and its binding to DNA was inhibited by SHP, resulting in the inhibition of PEPCK gene transcription. | SIGNOR-254831 |
Q7Z2W4 | O95453 | 2 | binding | up-regulates activity | 0.414 | We provide evidence indicating that ZAP selectively recruits cellular poly(A)-specific ribonuclease (PARN) to shorten the poly(A) tail of target viral mRNA and recruits the RNA exosome to degrade the RNA body from the 3′ end. | SIGNOR-261296 |
P15173 | P23409 | 1 | transcriptional regulation | up-regulates quantity by expression | 0.433 | [...] confirming that myogenin binds to the E1 and E2 E boxes located in close proximity to the MRF4 transcription start site. | SIGNOR-255642 |
P50148 | Q9NS75 | 2 | binding | up-regulates activity | 0.517 | 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-257024 |
Q01453 | P16144 | 2 | binding | up-regulates activity | 0.408 | PMP22 is in a complex with α6β4 integrin and laminin. PMP22 and β4 integrin are in a complex in a variety of cell types. The interaction with the integrins provides PMP22 with the ability to modulate the cell–ECM communications, as well as intracellular events. Signaling between the ECM and the intracellular compartment is essential for SC myelination, as well as cellular differentiation and motility, in general. The identification of PMP22 as a binding partner for an integrin signaling complex provides a major step toward understanding the role of this disease-linked molecule in the nervous system and in non-neural cell types. | SIGNOR-251896 |
P15559 | Q9Y4A8 | 0 | transcriptional regulation | down-regulates quantity by repression | 0.338 | Deletion mutation analysis revealed that Nrf3 repression of NQO1 gene expression required heterodimerization and DNA binding domains but not transcriptional activation domain of Nrf3. | SIGNOR-268976 |
Q9H9Z2 | P28482 | 0 | phosphorylation | down-regulates activity | 0.262 | Here we show that Lin28a is directly phosphorylated by ERK1/2 kinases at Ser-200. | SIGNOR-277338 |
P29474 | P41743 | 0 | phosphorylation | down-regulates activity | 0.2 | The phosphorylation of both S617 and S635 have also been shown to promote increased eNOS-derived NO release (Michell et al., 2002). The phosphorylaiton of S617 can be induced by PKA or Akt activity, and may serve to sensitize eNOS to calmodulin binding and modulate the phosphorylation of other eNOS sites | SIGNOR-251635 |
Q13485 | P49841 | 0 | phosphorylation | down-regulates quantity by destabilization | 0.398 | In the presence of FGF, Wnt potentiates TGF-β signaling by preventing Smad4 GSK3 phosphorylations that inhibit a transcriptional activation domain located in the linker region. | SIGNOR-276440 |
P50148 | O95136 | 2 | binding | up-regulates activity | 0.53 | 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-257215 |
P45983 | P61586 | 2 | binding | up-regulates activity | 0.827 | We found that in the human kidney epithelial cell line, 293T, Cdc42 and all Rho proteins, RhoA, RhoB, and RhoC, but not Rac or Ras can induce activation of JNK. | SIGNOR-258974 |
Q16659 | Q9UNH5 | 0 | dephosphorylation | down-regulates | 0.641 | Using ms analysis, we identified four novel phosphorylation sites, ser684, ser688, thr698 and ser705, located at the extreme c-terminus of erk3.alanine substitution of the four c-terminal phosphorylation sites markedly decreased the half-life of erk3 in mitosis, thereby linking phosphorylation to the stabilization of the kinase.we found that the phosphatases cdc14a and cdc14b (cdc is cell-division cycle) bind to erk3 and reverse its c-terminal phosphorylation in mitosis. | SIGNOR-164412 |
O43318 | P29350 | 0 | dephosphorylation | down-regulates activity | 0.295 | Mechanistically, the association of EHEC Tir with SHP-1 facilitated the recruitment of SHP-1 to TAK1 and inhibited TAK1 phosphorylation, which then negatively regulated K63-linked polyubiquitination of TAK1 and downstream signal transduction.|SHP-1 inhibits TAK1 activity to down-regulate signal transduction and subsequent cytokine production.Innate immune responses are achieved by the activation of several pathogen-recognition receptors (PRPs), including TLRs, retinoic acid inducible gene I (RIG-I)-like receptors (RLRs) and nucleotide-binding oligomerization domain (NOD)-like receptors (NLRs). | SIGNOR-277128 |
Q96GD4 | P53350 | 1 | phosphorylation | up-regulates activity | 0.599 | Aurora B phosphorylates PLK1 on Thr210 to activate its kinase activity at the kinetochores during mitosis.|Thus, we conclude that Aurora B indirectly promotes the phosphorylation of MCAK on Ser715 at the kinetochores through phosphorylation of PLK1 at Thr210 and its ensuing activation. | SIGNOR-279358 |
O14965 | P00533 | 1 | phosphorylation | up-regulates activity | 0.393 | Because AURKA associated with EGFR, we next investigated whether AURKA phosphorylates EGFR at Thr654 and Ser1046.|Protein phosphorylation profiling using an in situ proximity ligation assay: phosphorylation of AURKA-elicited EGFR-Thr654 and EGFR-Ser1046 in lung cancer cells. | SIGNOR-279589 |
P11908 | O95835 | 0 | phosphorylation | down-regulates quantity by destabilization | 0.2 | Recruitment of TRAF2 to PRPS1/2 requires phosphorylation of PRPS1 S285 or PRPS2 T285, which is mediated by low stiffness-activated large tumor suppressor (LATS)1/2 kinases.LATS1/2-dependent S/T285 phosphorylation is required for PRPS1/2 ubiquitination and degradation at low stiffness. | SIGNOR-276506 |
P48551 | P01574 | 2 | binding | up-regulates | 0.675 | Ifn-alpha, ifn-beta, and ifn-omega, induce somewhat different cellular effects but act through a common receptor complex, ifnar, composed of subunits ifnar-1 and ifnar-2. | SIGNOR-105934 |
P61586 | Q9Y653 | 2 | binding | up-regulates activity | 0.2 | Like many other adhesion GPCRs, GPR56 is cleaved via a GPCR autoproteolysis-inducing (GAIN) domain into N- and C-terminal fragments (GPR56N and GPR56C); | We demonstrate that ligand binding releases GPR56N from the membrane-bound GPR56C and triggers the association of GPR56C with lipid rafts and RhoA activation. | SIGNOR-253981 |
Q9UJQ4 | Q9BXF3 | 1 | transcriptional regulation | up-regulates quantity by expression | 0.2 | SALL4 activates Cecr2 by directly binging to its promotor region and CECR2 in turn promotes reprogramming through forming a SMARCA1-contained chromatin remodeling complex with its DTT domain. | SIGNOR-263893 |
Q06124 | P48357 | 2 | binding | up-regulates activity | 0.471 | Because the long leptin receptor lacking tyrosine 985 exhibits a significantly reduced ability to activate ERK phosphorylation, this residue is at least in part mediating stimulation of the ERK pathway by ObRb. This residue binds SHP-2 and is required for tyrosine phosphorylation of SHP-2 | SIGNOR-263506 |
Q9Y2G1 | Q02750 | 0 | phosphorylation | down-regulates activity | 0.258 | Mek1 phosphorylation of Ndt80 therefore provides an elegant way for cells to know when it is safe to enter the first meiotic division.|These observations suggest that phosphorylation of the DBD by Mek1 prevents Ndt80 from binding to MSEs and explains how Mek1 phosphorylation can inhibit Ndt80 activity. | SIGNOR-279416 |
P29322 | O43921 | 2 | binding | up-regulates | 0.75 | The activation of eph receptors by their ligands, which are membrane-anchored molecules, involves a cell-cell recognition event that often causes cell repulsion. Therefore, eph receptors mediate signals that can override cell adhesion. | SIGNOR-52269 |
P78406 | P59634 | 2 | binding | down-regulates activity | 0.2 | Orf6 of SARS-CoV antagonizes host interferon signaling by perturbing nuclear transport, and the NUP98-RAE1 interaction with Orf6 may perform the same function for SARS-CoV-2. | SIGNOR-260975 |
P24941 | P78317 | 1 | phosphorylation | up-regulates activity | 0.2 | Here we reported that CDK2 could phosphorylate RNF4 on T26 and T112 and enhance RNF4 E3 ligase activity, which is important for MDC1 degradation and proper HR repair during S phase. | SIGNOR-276900 |
P15173 | Q13683 | 1 | transcriptional regulation | up-regulates quantity by expression | 0.283 | Only myogenin and MyoD were able to efficiently trans-activate the alpha7 promoter-CAT construct (Fig. 7). Myogenin trans-activated the promoter by _2-fold whereas MyoD was able to trans-activate by nearly 4-fold, indicating that both of these factors may play a role in alpha7 gene expression during muscle development. | SIGNOR-241521 |
O14746 | P00519 | 0 | phosphorylation | down-regulates activity | 0.66 | These findings indicate that phosphorylation of hTERT by c-Abl is associated with inhibition of telomerase activity.|We also found that c-Abl phosphorylates hTERT and inhibits hTERT activity. | SIGNOR-279354 |
Q13489 | P57078 | 1 | polyubiquitination | up-regulates activity | 0.355 | CIAP1/2 are direct E3 ligases conjugating diverse types of ubiquitin chains to receptor interacting proteins kinases 1 to 4 (RIP1-4).Together, our results demonstrate that depleting cIAP1/2 inhibits RIP1-4 mediated NF-kB activation without affecting RIP auto-phosphorylation.Lysine residues K51 and K145 of RIP4 are critical for cIAP1-mediated ubiquitination and NF-kB activation. | SIGNOR-272709 |
Q96CV9 | Q9UHD2 | 2 | binding | up-regulates activity | 0.789 | Using biochemical experiments we showed that optineurin interacts with the protein kinase TBK1 and the ubiquitin ligase TRAF3. Furthermore, a mutation in optineurin that prevents the interaction with the small protein modifier ubiquitin (D474N) ablated the negative regulatory function of optineurin. | SIGNOR-262276 |
Q8IUQ4 | P98161 | 2 | binding | up-regulates activity | 0.333 | Full-length PC1 bound, stabilized and colocalized with Jade-1 and inhibited Jade-1 ubiquitination. Jade-1 ubiquitination was mediated by Siah-1, an E3 ligase that binds PC1. | SIGNOR-272916 |
Q9GZV5 | P06493 | 0 | phosphorylation | down-regulates activity | 0.258 | We found that TAZ is phosphorylated in vitro and in vivo by the mitotic kinase CDK1 at S90, S105, T326, and T346 during the G2/M phase of the cell cycle. Interestingly, mitotic phosphorylation inactivates TAZ oncogenic activity | SIGNOR-276518 |
P11308 | P48729 | 0 | phosphorylation | down-regulates quantity by destabilization | 0.2 | Using in vitro kinase assays, we further demonstrated that deletion of degron 1 largely abolished CKI-mediated phosphorylation of ERG (Figure S5B), indicating that serine residues within degron 1 are the major CKI phosphorylation sites. | SIGNOR-276935 |
Q96P20 | Q9UKC9 | 2 | binding | down-regulates quantity by destabilization | 0.351 | LPS exposure reduces the ubiquitin-mediated proteasomal processing of NALP3 by inducing levels of an E3 ligase component, FBXO3, which targets FBXL2. The latter is an endogenous mediator of NALP3 degradation. FBXL2 recognizes Trp-73 within NALP3 for interaction and targets Lys-689 within NALP3 for ubiquitin ligation and degradation. | SIGNOR-272432 |
P10275 | Q9NQU5 | 0 | phosphorylation | down-regulates quantity by destabilization | 0.2 | Furthermore, AR phosphorylation at Ser-578 by PAK6 promotes AR-E3 ligase murine double minute-2 (Mdm2) association, causing AR degradation upon androgen stimuli. | SIGNOR-279247 |
P63000 | P12931 | 0 | phosphorylation | up-regulates activity | 0.615 | In addition, Rac1 is phosphorylated at Y64 by FAK and Src kinases ( xref ); Y64 phosphorylation targets Rac1 to focal adhesions. | SIGNOR-280132 |
P51582 | P08754 | 2 | binding | up-regulates activity | 0.385 | 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-256870 |
P13224 | P17612 | 0 | phosphorylation | down-regulates activity | 0.312 | Platelet glycoprotein Ib beta is phosphorylated on serine 166 by cyclic AMP-dependent protein kinase. phosphorylation of this residue may contribute to the inhibitory actions of cyclic AMP by inhibiting collagen-induced polymerization of actin. | SIGNOR-249986 |
Q96RK0 | P51812 | 0 | phosphorylation | down-regulates | 0.2 | Specifically, 14-3-3 binds to p90(rsk)-phosphorylated ser?_??_ Of capic?_A thereby modulating dna binding to its hmg (high-mobility group) box, whereas erk phosphorylations prevent binding of a c-terminal nls (nuclear localization sequence) to importin ?4 (kpna3) | SIGNOR-169887 |
P37173 | P12931 | 0 | phosphorylation | up-regulates | 0.281 | Tbetarii can also be phosphorylated by src, a non-rtk, on y284, which can serve as a docking site for the recruitment of grb2 and shc, thereby bridging tbetarii to mapk activation. | SIGNOR-182963 |
P35368 | P38405 | 2 | binding | up-regulates activity | 0.278 | 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-256950 |
Q9Y2E6 | Q9UHD2 | 1 | ubiquitination | down-regulates | 0.584 | Nlrp4 negatively regulates type i interferon signaling by targeting the kinase tbk1 for degradation via the ubiquitin ligase dtx4 | SIGNOR-71565 |
P43403 | Q9UQC2 | 1 | phosphorylation | up-regulates activity | 0.46 | In the present study, we found that gab2 is phosphorylated by zap-70, associates with the tcr signaling complex, and acts as an inhibitory adaptor molecule via recruitment of shp-2 following tcr ligation. | SIGNOR-110731 |
Q9Y6R4 | O15169 | 2 | binding | up-regulates | 0.42 | Mekk4, also binds to axin in vivo and mediates axin-induced jnk activation. | SIGNOR-104003 |
Q12857 | Q9HD90 | 1 | transcriptional regulation | up-regulates quantity | 0.2 | 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-268891 |
P48735 | P36888 | 0 | phosphorylation | down-regulates activity | 0.421 | FLT3 promotes mIDH2 acetylation through Y107 phosphorylation of mIDH2 that enhances ACAT1 recruitment, | SIGNOR-267632 |
Q8IYA7 | Q13950 | 1 | transcriptional regulation | up-regulates quantity by expression | 0.301 | MKX is a meniscus-enriched transcription factor. In human meniscus cells, MKX regulates the expression of meniscus marker genes, OA-related genes, and other transcription factors, including Scleraxis (SCX), SRY Box 5 (SOX5), and Runt domain-related transcription factor 2 (RUNX2). | SIGNOR-267215 |
Q14653 | Q9UHD2 | 0 | 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 |
O14965 | Q8WV24 | 1 | phosphorylation | down-regulates quantity by destabilization | 0.447 | Aurora A directly phosphorylates PHLDA1 leading to its degradation. Aurora A phosphorylates PHLDA1 at Ser 98. | SIGNOR-273545 |
P28482 | Q9UQ13 | 1 | phosphorylation | down-regulates quantity by destabilization | 0.322 | Here, we showed that SHOC2, a RAS activator, is a FBXW7 substrate. Growth stimuli trigger SHOC2 phosphorylation on Thr507 by the mitogen-activated protein kinase (MAPK) signal, which facilitates FBXW7 binding for ubiquitylation and degradation. | SIGNOR-277442 |
P01024 | Q16581 | 2 | binding | up-regulates activity | 0.734 | A cDNA clone encoding the human C3a anaphylatoxin receptor (C3aR) was isolated from a pcDNAI/Amp expression library prepared from U-937 cells|The cDNA clone contained an insert of 4.3 kbp and was able to confer to transfected human HEK-293 cells the capacity to bind specifically iodinated human C3a. | SIGNOR-263451 |
Q5FBB7 | P06493 | 0 | phosphorylation | up-regulates activity | 0.2 | The complex between shugoshin and protein phosphatase 2A (Sgo1-PP2A) localizes to centromeres in mitosis, binds to cohesin in a reaction requiring Cdk-dependent phosphorylation of Sgo1, dephosphorylates cohesin-bound sororin, and protects a centromeric pool of cohesin from mitotic kinases and the cohesin inhibitor Wapl. | SIGNOR-265263 |
O43633 | Q9UN37 | 0 | cleavage | up-regulates activity | 0.911 | Here, we show, using high-speed atomic force microscopy and electron microscopy, that the AAA-type adenosine triphosphatase VPS4 constricts and cleaves ESCRT-III CHMP2A-CHMP3 helical filaments in vitro. Our results demonstrate that VPS4 actively constricts ESCRT-III filaments and cleaves them before their complete disassembly. We propose that the formation of ESCRT-III dome-like end caps by VPS4 within a membrane neck structure constricts the membrane to set the stage for membrane fission. | SIGNOR-260846 |
P19105 | Q13177 | 0 | phosphorylation | up-regulates activity | 0.495 | In this study we report that gamma-PAK, which is activated by the GTP-binding proteins Cdc42 and Rac, catalyses phosphorylation of intact non-muscle myosin II and isolated recombinant RLC. Phosphopeptide maps and phosphoamino acid analysis revealed that gamma-PAK phosphorylates Ser-19 but does not phosphorylate Thr-18.Taken together, these data suggest that myosin II activation by the p21-activated family of kinases may be physiologically important in regulating cytoskeletal organization. | SIGNOR-263020 |
Q8N0W4 | P78352 | 1 | relocalization | up-regulates activity | 0.754 | Like NRXNs, NLGNs bind to intracellular PDZ-domain proteins, but in contrast to NRXNs, NLGNs bind to class I PDZ domains such as those contained in PSD95, a postsynaptic MAGUK protein65. PSD95 and its homologues are centrally involved in recruiting glutamate receptors at postsynaptic sites66. Similarly to CASK, PSD95 binds to intracellular adaptor proteins, and especially to GKAP (a protein that binds to the guanylate-kinase domain of PSD95), which, in turn, binds to SHANK proteins (Fig. 1b). A possible role of these interactions is to recruit postsynaptic adaptor proteins to the site of synaptic junctions. | SIGNOR-264192 |
Q14653 | P05231 | 1 | transcriptional regulation | up-regulates quantity by expression | 0.406 | Recent reports show that in mice the microbiome, comprising commensal microorganisms that colonize body surfaces, promotes a partial and low-grade M1-like phenotype in macrophages throughout the body, including those in lymphoid organs (119, 120). This M1-like priming of macrophages induces chromatin remodeling with increased H3K4me3 marks at Ifnb, Il6, and Tnf promoters, which is associated with increased binding of NF-κB p65, IRF3, and Pol II upon cell stimulation | SIGNOR-251721 |
Q9Y6Q9 | O43791 | 2 | binding | down-regulates quantity by destabilization | 0.479 | Here, we analyzed changes in the ubiquitin landscape induced by prostate cancer-associated mutations of SPOP, an E3 ubiquitin ligase substrate-binding protein. SPOP mutants impaired ubiquitylation of a subset of proteins in a dominant-negative fashion. Of these, DEK and TRIM24 emerged as effector substrates consistently up-regulated by SPOP mutants. Up-regulation of DEK, TRIM24 and NCOA3 is a feature of prostate cancer SPOP mutations. | SIGNOR-272827 |
O75365 | P60484 | 1 | dephosphorylation | down-regulates quantity by destabilization | 0.296 | As expected, PRL3 clearly reduced PTEN phosphorylation at the tyrosine residue and PTEN protein in PRL3 overexpressing LO2 and HepG2 cell lines, with no significant changes in PRL3 (C104S) mutant cells.|PRL3 down-regulates PTEN expression, a negative regulator of the Akt pathway.11 Phosphorylation of PTEN at Tyr336 is required for maintenance of PTEN protein stability and prevention of PTEN degradation.17 We therefore speculated that PRL3 might dephosphorylate PTEN at tyrosine sites and consequently reduce the PTEN protein level. | SIGNOR-277010 |
O43516 | Q06187 | 0 | phosphorylation | up-regulates activity | 0.542 | Based on previous reports and the present data we suggest that Btk can induce WASP activation and also facilitates its subsequent inactivation through WIP phosphorylation.|We confirmed that Btk can indeed phosphorylate Y468 of baculovirus-generated human His-tagged WIP ( xref ), but that this is more difficult to show in cell extracts where WIP would be purified along with cellular WASP (). | SIGNOR-279801 |
Q04721 | P78504 | 2 | binding | up-regulates | 0.639 | Here we report the first x-ray structure of a functional fragment of a notch ligand, the dsl-egf3 domains of human jagged-1 (j-1dsl-egf3). The structure identifies a highly conserved face of the dsl domain and we show, by functional analysis of drosophila ligand mutants, that this surface is required for both cis- and trans-regulatory interactions with notch. | SIGNOR-81364 |
P24941 | P49916 | 1 | phosphorylation | down-regulates | 0.418 | Dna ligase iii_ is specifically phosphorylated in replicating cells by the cell cycle kinase cdk2. However, in response to oxidative dna damage, dna ligase iii_ is dephosphorylated in a pathway that is dependent upon the dna damage-activated, phosphatidylinositol 3-phosphate (pi3)1-related kinase atm. | SIGNOR-150121 |
P42345 | O60516 | 1 | phosphorylation | up-regulates | 0.358 | While promoting initiation of protein translation through mtor, eukaryoticinitiation factor 4e, and the ribosomal p70-s6 kinase. | SIGNOR-122035 |
P28482 | P15056 | 1 | phosphorylation | down-regulates activity | 0.628 | Erk-induced phosphorylation of b-raf on t753 promoted the disassembly of raf heterodimers, and the mutation of t753 prolonged growth factor-induced heterodimerization. The b-raf t753a mutant enhanced differentiation of pc12 cells, which was previously shown to be dependent on sustained erk signaling. Site is critical for v-src dependent modulation of slk kinase activity. | SIGNOR-236388 |
P31749 | P03372 | 1 | phosphorylation | up-regulates | 0.765 | Studies using mutants of er-alpha demonstrated that akt increased estrogen receptor activity through the amino-terminal activation function-1 (af-1). Serines s104 s106, s118, and s167 appear to play a role in the activation of er-alpha by akt. | SIGNOR-84963 |
Q9UHD2 | P11908 | 1 | phosphorylation | up-regulates activity | 0.2 | Here, we show that ionizing radiation results in TBK1-mediated phosphorylation of phosphoribosyl pyrophosphate synthetase (PRPS)1/2 at T228, thereby enhancing PRPS1/2 catalytic activity and promoting deoxyribonucleotide synthesis. | SIGNOR-277317 |
P16615 | P45984 | 0 | phosphorylation | up-regulates activity | 0.2 | JNK2 Enhances SERCA2 Function in a CaMKII-Independent Manner..|We found that JNK2 and SERCA2 proteins are physically associated with each other, and that JNK2 directly elevates the maximal rate of the SERCA2 activity by phosphorylating SERCA2. | SIGNOR-279540 |
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