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 |
|---|---|---|---|---|---|---|---|
Q13131 | P22460 | 1 | phosphorylation | down-regulates activity | 0.2 | Thus, AMPK directly phosphorylates the subunit of KV1.5 at Ser592 and, to a lesser extent, at Ser560 | SIGNOR-277814 |
O96017 | P21127 | 1 | phosphorylation | up-regulates activity | 0.2 | CHK2 kinase promotes pre-mRNA splicing via phosphorylating CDK11p110|Unexpectedly, CHK2 kinase constitutively phosphorylated CDK11(p110) in a DNA damage-independent manner. | SIGNOR-279458 |
O43683 | O43683 | 2 | phosphorylation | up-regulates activity | 0.2 | Conversely, Bub1 is an active kinase regulated by intra-molecular phosphorylation at the P+1 loop. | SIGNOR-277186 |
O75151 | P68431 | 1 | demethylation | down-regulates activity | 0.2 | PHF2, a jmjC demethylase, is enzymatically inactive by itself, but becomes an active H3K9Me2 demethylase through PKA-mediated phosphorylation. This modification leads to targeting of the PHF2–ARID5B complex to its target promoters, where it removes the repressive H3K9Me2 mark. | SIGNOR-264521 |
P48729 | P98177 | 1 | phosphorylation | down-regulates | 0.2 | Additionally, ck1, dyrk1a, and cdk2 also phosphorylate foxos at various sites to inhibit foxos activity. | SIGNOR-183664 |
Q9NY28 | P00533 | 1 | glycosylation | down-regulates activity | 0.2 | Interestingly, the O-GalNAcylation of EGFR, which is the key factor related to the metastasis cascade, was impacted by GALNT8. Furthermore, our results suggested that the GALNT8-mediated O-GalNAcylation led to the suppression of the EGFR signaling pathway and metastatic potential in breast cancer cells. | SIGNOR-269679 |
P59768 | P19174 | 1 | binding | up-regulates | 0.2 | Furthermore, this work suggested that the gbetagamma subunits released upon gi activation activated phospholipase c-gamma (plc-gamma) to produce inositol 3 phosphate (ip3) which would subsequently increase intracellular ca2+ abundance. | SIGNOR-199138 |
Q9NZ42 | P34925 | 1 | cleavage | up-regulates | 0.2 | Ryk activity is modulated through cleavage of its icd by gamma-secretase | SIGNOR-182145 |
P51956 | O95721 | 1 | phosphorylation | up-regulates activity | 0.2 | In the present study, we show that NEK3 (NIMA-never in mitosis gene A-related kinase 3)-mediated serine 105 (S105) phosphorylation of SNAP29 directs its membrane association, without which cells present defective focal adhesion formation, impaired Golgi structure and attenuated cellular recycling. Our results highlight the importance of NEK3-mediated S105 phosphorylation of SNAP29 for its membrane localization and for membrane fusion dependent processes. | SIGNOR-273708 |
P05771 | P21730 | 1 | phosphorylation | down-regulates | 0.2 | Dynamics of protein kinase c-mediated phosphorylation of the complement c5a receptor on serine 334. Analysis of c5ar ser/ala mutants that possess a single intact serine residue either at position 334 or at neighboring positions 327, 332, or 338 revealed functional redundancy of c-terminal phosphorylation sites since all 4 serine residues could individually support c5ar internalization and desensitization | SIGNOR-151011 |
Q03112 | O15123 | 1 | transcriptional regulation | up-regulates quantity by expression | 0.2 | We finally observed that the forced expression of Evi1 induced GATA-2 expression in a hematopoietic cell line, EML C1, along with GATA-1, Ang-1, Ang-2 and Tie2 | SIGNOR-266060 |
P19474 | P34897 | 1 | ubiquitination | down-regulates quantity | 0.2 | The expression of TRIM21, but not the expression of the ligase-dead (LD) mutant TRIM21 (C16A, C31A and H33W) 36, increased SHMT2 ubiquitylation, which suggests that TRIM21 is the E3 ligase for SHMT2 and that the E3 ligase activity of TRIM21 is required for SHMT2 ubiquitylation.|We found that the overexpression of TRIM21 increased the degradation of SHMT2 in high glucose conditions by binding more K63-ubiquitin. | SIGNOR-278792 |
P35790 | Q99541 | 1 | phosphorylation | down-regulates quantity by destabilization | 0.2 | In addition, as a protein kinase, CHKalpha2 phosphorylates PLIN2 at Tyrosine 232 and PLIN3 at Tyrosine 251. Phosphorylated PLIN2 and PLIN3 are separated from lipid droplets and degraded by Hsc70-mediated autophagy, thereby promoting lipid droplet lipolysis, fatty acid oxidation and glioblastoma growth | SIGNOR-267649 |
Q9UKB1 | Q9Y2X9 | 1 | ubiquitination | down-regulates quantity by destabilization | 0.2 | E3 ligase the beta-transducin repeat-containing protein 2 (beta-TrCP2) governs the ubiquitination and degradation of ZNF281. In human CRC specimens, endogenous beta-TrCP2 were inversely correlated with ZNF281. | SIGNOR-264897 |
P45452 | P02679 | 1 | cleavage | down-regulates quantity by destabilization | 0.2 | Matrix metalloproteinases collagenase-2, macrophage elastase, collagenase-3, and membrane type 1-matrix metalloproteinase impair clotting by degradation of fibrinogen and factor XII| We have now investigated the role of collagenase-2 (MMP-8), macrophage elastase (MMP-12), collagenase-3 (MMP-13), and membrane type 1-matrix metalloproteinase (MT1-MMP, MMP-14) in the degradation of fibrinogen and Factor XII of the plasma clotting system.|MMP-13 27YVATRDN g-chain| 20ADSGEGD a-chain| 124RNSVDXLNXN b-chain| 442LRTGKEKV a-chain | SIGNOR-263614 |
Q05655 | P49815 | 1 | phosphorylation | down-regulates activity | 0.2 | In vivo kinase analysis further indicated that both S932 and S939 are phosphorylated in response to translation inhibitors. Finally, phosphorylation defective TSC2 mutants (S932A and S939A single mutants and a S932A/S939A double mutant) failed to upregulate mTORC1 activity in the presence of translation inhibitors, suggesting that activation of mTORC1 by translation inhibitors is mediated by PKC-δ phosphorylation of TSC2 at S932/S939, which inactivates TSC. | SIGNOR-277427 |
P14384 | P69905 | 1 | cleavage | down-regulates activity | 0.2 | Both human plasma carboxypeptidase N (CPN) and membrane-bound carboxypeptidase M (CPM) released the C-terminal arginine (alpha-Arg141) of the alpha chain of human adult hemoglobin. Thus, the hydrolysis of hemoglobin by CPM and CPN demonstrated the contribution of the alpha-Arg141 residue to sustaining the tetrameric structure of hemoglobin and its normal oxygen affinity and vasoactivity. | SIGNOR-256507 |
Q12857 | A8MYZ6 | 1 | transcriptional regulation | down-regulates quantity | 0.2 | By integrating transcriptomic profiling (RNA-seq) of Nfia- and Nfix-deficient GNPs with epigenomic profiling (ChIP-seq against NFIA, NFIB and NFIX, and DNase I hypersensitivity assays), we reveal that these transcription factors share a large set of potential transcriptional targets, suggestive of complementary roles for these NFI family members in promoting neural development | SIGNOR-268875 |
O14965 | P57073 | 1 | phosphorylation | up-regulates activity | 0.2 | Therefore, Aurora-A not only directly phosphorylates SOX8 but also promotes SOX8 transcription indirectly by regulating c-Myc protein. | SIGNOR-280189 |
O15393 | P59594 | 1 | cleavage | up-regulates activity | 0.2 | Here, we demonstrate that SARS-CoV-2 uses the SARS-CoV receptor ACE2 for entry and the serine protease TMPRSS2 for S protein priming. | SIGNOR-260217 |
P55212 | P59595 | 1 | cleavage | up-regulates activity | 0.2 | Caspase-6 is activated through the intrinsic pathway and mediates C-terminal cleavage of SARS-CoV N at residues 400 and 403 | SIGNOR-260212 |
O94874 | P62805 | 1 | ubiquitination | up-regulates activity | 0.2 | Here we report that UFM1 specific ligase 1 (UFL1), an ufmylation E3 ligase, is important for ATM activation. | SIGNOR-265072 |
Q9P1A6 | Q9BYB0 | 1 | relocalization | up-regulates activity | 0.2 | SHANK proteins are ‘master’ scaffolding proteins that tether and organize intermediate scaffolding proteins. They are located at excitatory synapses, where they are crucial for proper synaptic development and function. SAPAP proteins subsequently bind to the PDZ domain of members of the SHANK protein family. SHANK proteins then bind to the actin cytoskeleton and to Homer protein, which in turn interacts with mGluRs. Through these extended links, PSD95, SAPAP, SHANK and Homer proteins form a quaternary complex that brings together mGluR and NMDAR complexes in the PSD (FIG. 3). | SIGNOR-264591 |
Q00987 | Q9BRP0 | 1 | ubiquitination | down-regulates quantity by destabilization | 0.2 | In breast cancer cells, MDM2 overexpression or p53 KD reduced OVOL2 protein expression, and the proteasome inhibitor MG132 blocked the MDM2 overexpression\u2010 or p53 KD\u2010mediated reduction in OVOL2 expression (Figure\u00a06B,C).|The E3 ubiquitin ligase MDM2 ubiquitinates and degrades the OVOL2 protein. | SIGNOR-278826 |
O94991 | Q15465 | 1 | binding | down-regulates activity | 0.2 | SLITRK5 interacts with SHH and PTCH1. Mechanistically, SLITRK5 binds to hedgehog ligands via its extracellular domain and interacts with PTCH1 via its intracellular domain. SLITRK5 is present in the primary cilium, and loss of SLITRK5 enhances SMO ciliary enrichment upon SHH stimulation. Thus, SLITRK5 is a negative regulator of hedgehog signaling in osteoblasts that may be attractive as a therapeutic target to enhance bone formation. | SIGNOR-268437 |
Q9UHD2 | P31645 | 1 | phosphorylation | up-regulates activity | 0.2 | Taken together, our data suggest that TBK1 expression promotes the general cellular clearance mechanism of soluble HTT and prevents its accumulation and aggregation by enhancing autophagy.|This confirmed that TBK1 phosphorylated endogenous HTT at S13 (Fig XREF_FIG G and H). | SIGNOR-278384 |
P22607 | Q9UPZ9 | 1 | phosphorylation | down-regulates activity | 0.2 | FGF signaling partially abolished ICK's kinase activity, through FGFR-mediated ICK phosphorylation at conserved residue Tyr15, which interfered with optimal ATP binding. | SIGNOR-277436 |
P00519 | Q8WYQ5 | 1 | phosphorylation | up-regulates activity | 0.2 | The kinase ABL phosphorylates the microprocessor subunit DGCR8 to stimulate primary microRNA processing in response to DNA damage. When coexpressed in HEK293T cells, ABL phosphorylated DGCR8 at Tyr(267). | SIGNOR-262604 |
P49841 | Q92585 | 1 | phosphorylation | down-regulates | 0.2 | We found that gsk3beta inhibits maml1 transcriptional activity by directly targeting the n-terminal domain of maml1 | SIGNOR-187896 |
P00519 | Q13148 | 1 | phosphorylation | up-regulates quantity | 0.2 | The phosphorylation of tyrosine 43 of TDP-43 by c-Abl led to increased TDP-43 levels in the cytoplasm and increased the formation of G3BP1-positive stress granules in SH-SY5Y cells. | SIGNOR-279135 |
O60674 | P48029 | 1 | relocalization | down-regulates activity | 0.2 | Janus-activated kinase-2 (JAK2) participates in the regulation of the Na⁺-coupled glucose transporter SGLT1 and the Na⁺-coupled amino acid transporter SLC6A19. JAK2 is a novel regulator of the creatine transporter SLC6A8, which downregulates the carrier, presumably by interference with carrier protein insertion into the cell membrane. | SIGNOR-265781 |
Q05655 | Q13541 | 1 | phosphorylation | down-regulates activity | 0.2 | As shown for serum, phosphorylation of 4E-BP1 by PKCdelta inhibits the interaction between 4E-BP1 and eIF4E and stimulates cap-dependent translation.|Here we demonstrate that protein kinase Cdelta (PKCdelta) associates with RAFT1 and that PKCdelta is required for the phosphorylation and inactivation of 4E-BP1. | SIGNOR-279100 |
Q8NEG4 | P48729 | 1 | binding | up-regulates quantity | 0.2 | We identified members of the FAM83 family of proteins as partners of CK1 in cells. All eight members of the FAM83 family (FAM83A–H) interacted with the α and α-like isoforms of CK1; FAM83A, -B, -E, and -H also interacted with the δ and ε isoforms of CK1. The intrinsic catalytic activity of CK1 is not affected by or required for the association of CK1 with FAM83 proteins. Our findings imply that the DUF1669 domains of FAM83 proteins anchor CK1 α, α-like, δ, and ε isoforms in specific subcellular compartments and potentially mediate their association with substrates. | SIGNOR-273751 |
Q92585 | P68431 | 1 | acetylation | down-regulates activity | 0.2 | The n-terminal domain of maml1 directly interacts with both p300 and histones, and the p300-maml1 complex specifically acetylates histone h3 and h4 tails in chromatin. | SIGNOR-153038 |
P50281 | P02679 | 1 | cleavage | down-regulates quantity by destabilization | 0.2 | Matrix metalloproteinases collagenase-2, macrophage elastase, collagenase-3, and membrane type 1-matrix metalloproteinase impair clotting by degradation of fibrinogen and factor XII| We have now investigated the role of collagenase-2 (MMP-8), macrophage elastase (MMP-12), collagenase-3 (MMP-13), and membrane type 1-matrix metalloproteinase (MT1-MMP, MMP-14) in the degradation of fibrinogen and Factor XII of the plasma clotting system.|MMP-14 27YVATRDN g-chain| 105XDAATLKSR g-chain | 92LTYNPDES g-chain |105LTTNIXEXL a-chain|433LVTSKGDKE a-chain| 117FXSANNRD a-chain | SIGNOR-263616 |
P06493 | Q9C0C7 | 1 | phosphorylation | up-regulates activity | 0.2 | CDK1 phosphorylates AMBRA1 at T1209 and S1223. |CDK1-mediated phosphorylation primes PLK1 phosphorylation on AMBRA1|In this work, we show that AMBRA1 is sequentially phosphorylated at mitosis by CDK1 and PLK1 on multiple sites. In particular, CDK1 is responsible for the early phosphorylations on T1209 and S1223, and it promotes additional late phosphorylation events by PLK1 on AMBRA1. Altogether, these phosphorylation events are critical for proper spindle function and orientation. Indeed, phosphorylated AMBRA1 can interact with NUMA1 and is responsible for NUMA1 proper localization at the cell cortex. Moreover, we observe that loss of AMBRA1 leads to PLK1 protein stabilization and to an increase in phospho-NUMA1 levels which, in turn, contributes to spindle orientation defects. | SIGNOR-272968 |
P10276 | Q9NPD5 | 1 | transcriptional regulation | up-regulates quantity by expression | 0.2 | Taken together, these findings suggest that the LPS-induced down-regulation of Oatp4 is likely due to reduction in the binding of HNF1alpha, C/EBP, HNF3, and RXR:RAR to the Oatp4 promoter. | SIGNOR-268989 |
Q9Y5I2 | P05556 | 1 | binding | up-regulates activity | 0.2 | The clustered protocadherins comprise the largest subfamily of the cadherin superfamily and are predominantly expressed in the nervous system. Pcdh-alpha proteins interact with beta1-integrin to promote cell adhesion. | SIGNOR-265664 |
Q7LBC6 | Q07869 | 1 | transcriptional regulation | up-regulates quantity by expression | 0.2 | We show that Jhdm2a expression is induced by beta-adrenergic stimulation, and that Jhdm2a directly regulates peroxisome proliferator-activated receptor alpha (Ppara) and Ucp1 expression. | SIGNOR-266637 |
P11362 | Q96QU1 | 1 | phosphorylation | up-regulates activity | 0.2 | FGFR1 mediated protocadherin-15 loading mediates cargo specificity during intraflagellar transport in inner ear hair-cell kinocilia.|We find that on activation, FGFR1 binds and phosphorylates Pcdh15. | SIGNOR-280014 |
P30530 | Q8NB16 | 1 | phosphorylation | up-regulates quantity by stabilization | 0.2 | TAM kinases phosphorylate MLKL to promote necroptosis. MLKL is then recruited to the plasma membrane, where TAM kinases phosphorylate MLKL at Tyr376 (Figure 5G, step 5), promoting its oligomerization and formation of membrane-rupturing pores that result in necrotic cell death (Figure 5G, step 6). | SIGNOR-274119 |
P27361 | Q9NYV6 | 1 | phosphorylation | up-regulates | 0.2 | Erk-dependent phosphorylation of the transcription initiation factor tif-ia is required for rna polymerase i transcription and cell growth. phosphopeptide mapping and mutational analysis reveals two serine residues (s633 and s649) that are phosphorylated by erk and rsk kinases. Replacement of s649 by alanine inactivates tif-ia, inhibits pre-rrna synthesis, and retards cell growth. | SIGNOR-98984 |
P17612 | P84243 | 1 | phosphorylation | up-regulates activity | 0.2 | Identification of a novel phosphorylation site on histone h3 coupled with mitotic chromosome condensation. | SIGNOR-70424 |
Q9UQ80 | P07288 | 1 | transcriptional regulation | down-regulates quantity by repression | 0.2 | Ectopic expression of ebp1, a member of the PA2G4 family, inhibits the proliferation and induces the differentiation of human breast and prostate cancer cell lines. Ebp1 inhibits transcription of E2F1 and androgen receptor regulated genes such as prostate specific antigen (PSA) through its interactions with histone deacetylases (HDACs) | SIGNOR-253662 |
Q9HDB5 | Q14118 | 1 | binding | up-regulates activity | 0.2 | 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-265462 |
P45983 | Q96FI4 | 1 | phosphorylation | up-regulates activity | 0.2 | These data confirm that NEIL1 can be phosphorylated by JNK1 in vitro at S207, S306, and S61. | SIGNOR-278315 |
P24723 | P09211 | 1 | phosphorylation | up-regulates activity | 0.2 | Peptide phosphorylation analyses and both phosphorylation and enzyme kinetic studies with GSTP1 proteins mutated at candidate amino acid residues established Ser-42 and Ser-184 as putative phospho-acceptor residues for both kinases in the GSTP1 protein. Together, these findings show PKA- and PKC-dependent phosphorylation as a significant post-translational mechanism of regulation of GSTP1 function. Together, these results further support S42 and S184 as major phosphor-acceptor residues for PKA and PKC and suggest that the increased activity of the phospho-GSTP1 was not simply a consequence of the negative charge introduced in the GSTP1 protein by the phosphate group.All eight PKC isoforms, PKC-α, PKC-βI, PKC-βII, PKC-ε, PKC-γ, PKC-η, and PKC-ζ phosphorylated the GSTP1 protein efficiently | SIGNOR-276014 |
Q9UHD2 | O95865 | 1 | phosphorylation | down-regulates activity | 0.2 | TANK-binding kinase 1 (TBK1), a kinase downstream of MAVS, inhibited DDAH2 by phosphorylating DDAH2 at multiple sites. |The T203D, T211D, S245D, and S253D mutations significantly reduced the inhibitory effect of DDAH2 on RLR signaling, suggesting that phosphorylation of these residues was critical for DDAH2 to inhibit activation o | SIGNOR-275648 |
Q68CZ1 | Q04206 | 1 | demethylation | down-regulates | 0.2 | Fbxl11 and nsd1 have opposite effects on nf-kb; both bind to p65 subunit after activation of nf-kb. / nsd1 activates nf-kb and reverses the inhibitory effect of fbxl11 / these data confirm that fbxl11 and nsd1 constitute an enzyme pair that methylates and demethylates p65 on k218 and 221 in response to cytokine stimulation. | SIGNOR-163320 |
Q99698 | P61020 | 1 | binding | down-regulates activity | 0.2 | Mauve interacts with Rab5, Msps, and gamma-tubulin|Mauve/LYST opposes Rab5, which promotes vesicle fusion affecting PCM recruitment | SIGNOR-266002 |
Q9P286 | O95831 | 1 | phosphorylation | down-regulates activity | 0.2 | Our results show that PAK5 can phosphorylate Thr-281 of AIF, which is included in its NLS1 sequence.|These results suggested that PAK5 inhibited AIF from entering the nucleus through phosphorylation of AIF T281 site, thus inhibiting cell apoptosis. | SIGNOR-279085 |
Q9Y572 | Q13263 | 1 | phosphorylation | down-regulates activity | 0.2 | These results indicate that TRIM28 phosphorylation at S473 is RIPK3-dependent and suggest that RIPK1/RIPK3 activation induces TRIM28 phosphorylation at S473, which may play an important role in the regulation of transcriptional activity. | SIGNOR-279107 |
Q92777 | P60709 | 1 | 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-269182 |
Q15139 | Q96A00 | 1 | phosphorylation | up-regulates activity | 0.2 | 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-249260 |
Q9Y5H9 | Q9Y5G3 | 1 | binding | up-regulates activity | 0.2 | The clustered protocadherins comprise the largest subfamily of the cadherin superfamily and are predominantly expressed in the nervous system. Pcdh-alpha proteins interact with beta1-integrin to promote cell adhesion. They also form oligomers with Pcdh-gamma proteins at the same membrane sites. | SIGNOR-265681 |
Q8TD10 | P62745 | 1 | binding | up-regulates activity | 0.2 | MIPOL1 protein interacts with tumor suppressor RhoB and enhances its cellular activity | SIGNOR-261134 |
Q8TCJ0 | P19419 | 1 | binding | down-regulates quantity by destabilization | 0.2 | The F-box protein FBXO25 promotes the proteasome-dependent degradation of ELK-1 protein. FBXO25 is one of the 69 known human F-box proteins that serve as specificity factors for a family of ubiquitin ligases composed of SKP1, Rbx1, Cullin1, and F-box protein (SCF1) that are involved in targeting proteins for degradation across the ubiquitin proteasome system. FBXO25 interacted with and mediated the ubiquitination and proteasomal degradation of ELK-1 in HEK293T cells. | SIGNOR-272127 |
Q92560 | P42772 | 1 | transcriptional regulation | up-regulates quantity by expression | 0.2 | Since we found that ASXL1 and BAP1 both are enriched at the INK4B locus, our results suggest that activation of the INK4B locus requires ASXL1/BAP1-mediated deubiquitinylation of H2AK119ub1. | SIGNOR-241656 |
P23470 | P29353 | 1 | dephosphorylation | down-regulates activity | 0.2 | PTPRG activation by the P1-WD peptide affected the tyrosine phosphorylation of several signaling molecules. Data analysis identified 31 molecules whose phosphorylation was modified in a statistically significant manner (Table I). inhibition of ABL1, BMX, BTK, DAB1, ITGB1, JAK2, KDR, KIT, LIMK1, MET, PDGFRB, SHC1, and VCL correlates with tyrosine dephosphorylation. In contrast, SRC inhibition correlates with hyperphosphorylation of the inhibitory Tyr530 residue and with dephosphorylation of the activatory Tyr419. Moreover, CDK2 and CTTN inhibition correlates with a hyperphosphorylation of the inhibitory Tyr15 and Tyr470, respectively. In contrast, a subgroup of 13 proteins, including BLNK, DOK2, ERBB2, GRIN2B, INSR, PDGFRA, PRKCD, PXN, STAT1, STAT2, STAT3, STAT5A, and ZAP70, appears to be activated by PTPRG activity. | SIGNOR-254724 |
P26927 | P17252 | 1 | phosphorylation | up-regulates activity | 0.2 | Thus, the phosphorylation of PKCα at Ser226 and Thr228 by Mst1 and Mst2 is required for the optimal activation of PKCα. | SIGNOR-277179 |
P51955 | Q9NZQ7 | 1 | phosphorylation | up-regulates quantity by stabilization | 0.2 | NEK2 interacts with PD-L1, phosphorylating the T194/T210 residues and preventing ubiquitin-proteasome pathway-mediated degradation of PD-L1 in ER lumen. | SIGNOR-277314 |
Q8IYT8 | Q9UGI9 | 1 | phosphorylation | down-regulates | 0.2 | Ulk1/2 in turn phosphorylates all three subunits of ampk and thereby negatively regulates its activity. | SIGNOR-173095 |
Q6ZVD8 | Q13043 | 1 | dephosphorylation | up-regulates activity | 0.2 | PHLPPs dephosphorylate Mst1 on the T387 inhibitory site, which activate Mst1 and its downstream effectors p38 and JNK to induce apoptosis. | SIGNOR-248730 |
Q5TCX8 | O15111 | 1 | phosphorylation | down-regulates activity | 0.2 | Immunoprecipitation and in vitro kinase analysis revealed that MLK4 physically interacts with both IKKalpha and beta, but preferentially phosphorylates IKKalpha over IKKbeta (XREF_FIG | SIGNOR-279067 |
Q86Y13 | Q8IUE6 | 1 | monoubiquitination | up-regulates activity | 0.2 | 2A-HUB catalyzes monoubiquitination of H2A at lysine 119, functioning as a combinatoric component of the repression machinery required for specific gene regulation programs. Thus, 2A-HUB mediates a selective repression of a specific set of chemokine genes in macrophages, critically modulating migratory responses to TLR activation. H2A monoubiquitination acts to prevent FACT recruitment at the transcriptional promoter region, blocking RNA polymerase II release at the early stage of elongation. | SIGNOR-271758 |
P29375 | P84243 | 1 | 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-264301 |
Q96RG2 | Q96RG2 | 2 | phosphorylation | up-regulates activity | 0.2 | We present evidence that the activity of pask is regulated by two mechanisms. Autophosphorylation at two threonine residues located within the activation loop significantly increases catalytic activity. | SIGNOR-109481 |
O15550 | P15036 | 1 | transcriptional regulation | down-regulates quantity by repression | 0.2 | Our findings reveal a dual role for UTX in suppressing acute myeloid leukaemia via repression of oncogenic ETS and upregulation of tumor suppressive GATA programs. several ETS transcription factors, including Elf4, Etv6, Erg, Fli1, Ets2, Spi1 and Elk3 were upregulated immediately after Utx loss in the preleukaemic phase | SIGNOR-260035 |
O00398 | P08754 | 1 | binding | up-regulates activity | 0.2 | Here we systematically quantified ligand-induced interactions between 148 GPCRs and all 11 unique G alpha subunit C-termini. For each receptor, we probed chimeric G alpha subunit activation via a transforming growth factor-alpha (TGF alpha) shedding response in HEK293 cells lacking endogenous Gq/11- and G12/13- signaling. | We defined positive coupling if any member of the subfamily scored LogRAi ≥ -1 and negative coupling if all of the members scored LogRAi < -1 (Figure 3A-B). ROC analysis gives AUC = 0.78 (Figure S4A) when considering high-confidence known coupling data and suggested a threshold of LogRAi ≥ -1.0 for defining true couplings. | The score associated to this interaction has a LogRAi ≥ -1.0. | SIGNOR-256869 |
P78527 | O75030 | 1 | phosphorylation | up-regulates activity | 0.2 | These results suggest that DNA-PK can target MITF-S325 for phosphorylation. In melanocytes and melanoma cells, MITF is rapidly phosphorylated by DNA-PK and interacts with NBS1–RAD50 but not MRE11, destabilizing the MRN complex. | SIGNOR-277899 |
P17612 | Q15052 | 1 | phosphorylation | down-regulates activity | 0.2 | ARHGEF6 is a Rho guanine nucleotide exchange factor for Rac1 and constitutively bound to GIT1. NO and PGI2 activate PKG and PKA, respectively and both kinases phosphorylate ARHGEF6 on Ser-684 and possibly on Ser-640. Phosphorylation of ARHGEF6 results in the assembly of a GIT1-ARHGEF6–14-3-3 complex. These changes might contribute to PGI2- and NO-mediated Rac1 inhibition. | SIGNOR-272162 |
Q9Y2T4 | P12931 | 1 | binding | down-regulates activity | 0.2 | We show that PR55gamma binds c-SRC and modulates the phosphorylation of serine 12 of c-SRC, a residue we demonstrate to be required for JNK activation by c-SRC | SIGNOR-247966 |
P25105 | P63096 | 1 | binding | up-regulates activity | 0.2 | Here we systematically quantified ligand-induced interactions between 148 GPCRs and all 11 unique G alpha subunit C-termini. For each receptor, we probed chimeric G alpha subunit activation via a transforming growth factor-alpha (TGF alpha) shedding response in HEK293 cells lacking endogenous Gq/11- and G12/13- signaling. | We defined positive coupling if any member of the subfamily scored LogRAi ≥ -1 and negative coupling if all of the members scored LogRAi < -1 (Figure 3A-B). ROC analysis gives AUC = 0.78 (Figure S4A) when considering high-confidence known coupling data and suggested a threshold of LogRAi ≥ -1.0 for defining true couplings. | The score associated to this interaction has a LogRAi ≥ -1.0. | SIGNOR-257061 |
Q96RU7 | Q8NHY2 | 1 | binding | up-regulates activity | 0.2 | TRB3 appears to inhibit ACC activity by functioning as an adaptor for COP1. Taken together, these results suggest that TRB3 may promote loss of fat by mediating the COP1-dependent ubiquitination and inactivation of ACC. Taking these results together, we propose that TRB3 may protect against diet-induced obesity by stimulating fatty acid oxidation in adipose during fasting through the COP1-mediated ubiquitination and degradation of ACC (Fig. 4D). | SIGNOR-271603 |
Q86UZ6 | P15018 | 1 | transcriptional regulation | up-regulates quantity by expression | 0.2 | ZBTB46 binds directly to the LIF regulatory sequence and enhances its transcription. Our study confirmed a novel positive association between ZBTB46 activity and LIF levels in prostate cancer tissues and cells. Under androgen regulation, low levels of ZBTB46 are an essential transcriptional factor for maintaining LIF-STAT3 signaling, while the loss of androgen signaling or inhibition of AR signaling causes LIF-enhanced therapeutic resistance and CRPC characteristics through the upregulation of ZBTB46. We also found that LIF activation drives malignant progression and NE-like reprogramming in prostate cancer by activating STAT3 signaling. | SIGNOR-277988 |
P17252 | P29972 | 1 | phosphorylation | up-regulates | 0.2 | Activation of protein kinase c (pkc) by 1-oleoyl-2-acetyl-sn-glycerol (oag) induced a marked increase of aqp1-dependent water permeability. This regulation was abolished in mutated aqp1 channels lacking both consensus pkc phosphorylation sites thr(157) and thr(239) (termed aqp1 deltapkc). | SIGNOR-155106 |
Q96HS1 | P48163 | 1 | dephosphorylation | up-regulates activity | 0.2 | PGAM5-mediated dephosphorylation of malic enzyme 1 (ME1) at S336 allows increased ACAT1-mediated K337 acetylation, leading to ME1 dimerization and activation, both of which are reversed by NEK1 kinase-mediated S336 phosphorylation. SIRT6 deacetylase antagonizes ACAT1 function in a manner that involves mutually exclusive ME1 S336 phosphorylation and K337 acetylation. | SIGNOR-275569 |
Q9NRD0 | P09211 | 1 | binding | down-regulates quantity by destabilization | 0.2 | Here, we show that loss of FBX8 accelerates chemical-induced colon tumorigenesis. FBX8 directly targets GSTP1 for ubiquitin-mediated proteasome degradation in CRC. | SIGNOR-272304 |
P01024 | P01024 | 2 | cleavage | up-regulates activity | 0.2 | C3 autoactivates in a process known as “tick-over,” which is characterized by spontaneous hydrolysis of a reactive thiol-ester to generate C3(H2O). Although C3(H2O)Bb produces only relatively small amounts of C3b compared to the other C3 convertases, it nevertheless generates enough C3b to set the C3 convertase amplification loop in motion. | SIGNOR-263483 |
P35637 | P57678 | 1 | relocalization | up-regulates activity | 0.2 | Here, we report that FUS associates with the SMN complex, mediated by U1 snRNP and by direct interactions between FUS and SMN.|The FUS IP and pulldown revealed that FUS also associates with components of the SMN complex, including SMN and Gemins 4 and 6 |Remarkably, the number of SMN-stained nuclear bodies was dramatically reduced in the FUS knockdown cells | SIGNOR-262105 |
Q9P286 | Q92934 | 1 | phosphorylation | down-regulates activity | 0.2 | P21-Activated kinase 5 (Pak5) localizes to mitochondria and inhibits apoptosis by phosphorylating BAD. Pak5 phosphorylates BAD Ser-112 | SIGNOR-250247 |
Q92570 | Q07812 | 1 | transcriptional regulation | up-regulates quantity by expression | 0.2 | Over-expression of NR4A3 attenuated proliferation of cancer cells and promoted apoptosis by augmenting the expression of pro-apoptotic genes, PUMA and Bax. | SIGNOR-259397 |
Q504Q3 | Q99708 | 1 | deubiquitination | up-regulates activity | 0.2 | Here, we identify that USP52 directly interacts with and deubiquitinates CtIP, thereby promoting DNA end resection and HR. Mechanistically, USP52 removes the ubiquitination of CtIP to facilitate the phosphorylation and activation of CtIP at Thr-847. In addition, USP52 is phosphorylated by ATM at Ser-1003 after DNA damage, which enhances the catalytic activity of USP52. | SIGNOR-273509 |
P05771 | Q96D31 | 1 | 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 |
Q13309 | O75874 | 1 | ubiquitination | down-regulates quantity by destabilization | 0.2 | During the cell cycle S phase, Cyclin A-CDK2 phosphorylates IDH1 on its Threonine 157 residue (Threonine 197 in IDH2) to facilitate its recognition and ubiquitination by Skp2 E3 ubiquitin, followed by degradation through 26S proteasome | SIGNOR-267625 |
P05129 | Q14155 | 1 | phosphorylation | up-regulates | 0.2 | Pkc_ directly phosphorylates _pix at ser583 and indirectly at ser340 in cells. herefore, we propose that pkc_ positively modulates dopamine release through _2pix phosphorylation. The pkc_-_pix-cdc42/rac1 phosphorylation axis may provide a new therapeutic target for the treatment of parkinsonian syndrome | SIGNOR-205238 |
Q9ULU4 | Q9ULU4 | 2 | binding | up-regulates activity | 0.2 | We identified ZMYND8 as a transcriptional corepressor of the H3K4 demethylase JARID1D|Co-immunoprecipitation between ectopically expressed FLAG-tagged JARID1D and endogenous ZMYND8 protein. | SIGNOR-262037 |
Q86VG3 | P20290 | 1 | binding | down-regulates activity | 0.2 | Furthermore, we co-immunoprecipitated HEPIS with BTF3, a component of the RNA pol II initiation complex, and observed reduced proliferation of HeLa cells transfected with the HEPIS gene. | SIGNOR-260252 |
O14994 | P60709 | 1 | 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 |
P06241 | P06241 | 2 | phosphorylation | up-regulates activity | 0.2 | Activated Fyn furthermore undergoes autophosphorylation on Tyr30, Tyr39 and Tyr420. Tyr28 This site is also a Fyn autophosphorylation site When Fyn mutants with Tyr28, Tyr30 or Tyr39 replaced with phenylalanine residues were transfected into NIH3T3 cells a decreased activation after PDGF stimulation was seen, suggesting a functional importance of the N-terminal tyrosine phosphorylation of Fyn. | SIGNOR-251167 |
P68400 | Q9ULV4 | 1 | phosphorylation | up-regulates | 0.2 | We demonstrate that crn2 is a binding partner and substrate of protein kinase ck2, which phosphorylates crn2 at s463 in its c-terminal coiled coil domain | SIGNOR-196193 |
Q9HC98 | P35613 | 1 | phosphorylation | down-regulates activity | 0.2 | These results indicate that NEK6 directly interacts with CD147 and phosphorylates the protein at serine-252 in Huh-7 cells. | SIGNOR-273882 |
Q9UN75 | P05556 | 1 | binding | up-regulates activity | 0.2 | The clustered protocadherins comprise the largest subfamily of the cadherin superfamily and are predominantly expressed in the nervous system. Pcdh-alpha proteins interact with beta1-integrin to promote cell adhesion. | SIGNOR-265673 |
Q86TM6 | P46527 | 1 | ubiquitination | down-regulates quantity by destabilization | 0.2 | The E3 ligase activity of Hrd1 is required for p27 kip1 ubiquitination, because co-expression of Hrd1 containing an alanine point mutation at the critical cysteine within the RING E3 ligase region (Hrd1/CA) failed to enhance p27 kip1 ubiquitination (XREF_FIG).|Therefore, our study identifies Hrd1 as an E3 ligase of p27 kip1 and establishes that Hrd1 mediated p27 kip1 degradation plays an important role in T-cell immunity. | SIGNOR-278786 |
P49841 | Q96F46 | 1 | phosphorylation | down-regulates quantity by destabilization | 0.2 | Glycogen synthase kinase 3 (GSK3) constitutively bound to and phosphorylated IL-17RA at T780, leading to ubiquitination and proteasome-mediated degradation of IL-17RA, thus inhibiting IL-17-mediated inflammation. | SIGNOR-277205 |
Q12778 | O00330 | 1 | transcriptional regulation | down-regulates quantity by repression | 0.2 | Our genetic analysis indicates that Foxo1 is an effector of Irs2 signaling in pancreatic β cells. Foxo1 inactivation leads to increased Pdx1 expression and β cell proliferation. Since Foxo1 is expressed in a subset of cells embedded within pancreatic ducts, we propose that, in quiescent duct-associated cells that are not committed to a β cell fate, Foxo1 acts as a transcriptional brake on Pdx1. We propose the following mechanism of Foxo1 regulation: small quantities of insulin are released in the pancreatic duct (31), where they activate signaling (32) in the Foxo1-positive duct cell subset, leading to Foxo1 nuclear exclusion and Pdx1 expression. | SIGNOR-278151 |
O75398 | P60763 | 1 | transcriptional regulation | up-regulates quantity by expression | 0.2 | Affymetrix gene profiling studies revealed Rac3 as a potential target gene and quantitative RT-PCR analysis confirmed that Rac3 was upregulated by Deaf-1 in immortalized mouse mammary epithelial cells. | SIGNOR-269059 |
Q86UY5 | Q8N752 | 1 | binding | up-regulates quantity | 0.2 | We identified members of the FAM83 family of proteins as partners of CK1 in cells. All eight members of the FAM83 family (FAM83A–H) interacted with the α and α-like isoforms of CK1; FAM83A, -B, -E, and -H also interacted with the δ and ε isoforms of CK1. The intrinsic catalytic activity of CK1 is not affected by or required for the association of CK1 with FAM83 proteins. Our findings imply that the DUF1669 domains of FAM83 proteins anchor CK1 α, α-like, δ, and ε isoforms in specific subcellular compartments and potentially mediate their association with substrates. | SIGNOR-273756 |
Q9UQB3 | Q96RT1 | 1 | binding | up-regulates activity | 0.2 | We characterized the interactions between the Erbin PDZ domain and both ARVCF and δ-catenin in vitro and in vivo. endogenous δ-catenin and Erbin co-localized in and co-immunoprecipitated from neurons. These results suggest that δ-catenin and ARVCF may function to mediate the association of Erbin with the junctional cadherin-catenin complex. | SIGNOR-252120 |
Q8TAB3 | Q16445 | 1 | binding | up-regulates quantity by stabilization | 0.2 | Here, we found that PCDH19 binds the alpha subunits of GABAAR and regulates its surface availability and currents in cultured hippocampal neurons. The PCDH19 gene (Xp22.1) encodes the cell-adhesion protein protocadherin-19 (PCDH19) and is responsible for a neurodevelopmental pathology characterized by female-limited epilepsy, cognitive impairment and autistic features, the pathogenic mechanisms of which remain to be elucidated. Here, we identified a new interaction between PCDH19 and GABAA receptor (GABAAR) alpha subunits in the rat brain. PCDH19 shRNA-mediated downregulation reduces GABAAR surface expression and affects the frequency and kinetics of miniature inhibitory postsynaptic currents (mIPSCs) in cultured hippocampal neurons. | SIGNOR-267221 |
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