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 |
|---|---|---|---|---|---|---|---|
O14904 | O75581 | 2 | binding | up-regulates | 0.64 | Wnt proteins bind to the frizzled receptors and lrp5/6 co-receptors, and through stabilizing the critical mediator betBeta-catenin, initiate a complex signaling cascade that plays an important role in regulating cell proliferation and differentiation. | SIGNOR-132076 |
O15392 | P55211 | 2 | binding | down-regulates | 0.504 | Survivin (an inhibitor of apoptosis) phosphorylation on thr34 may regulate apoptosis at cell division via an interaction with caspase-9. | SIGNOR-84065 |
Q9BQE3 | Q8NG68 | 0 | tyrosination | down-regulates | 0.473 | Tubulin tyrosine ligase (ttl) adds a c-terminal tyr to __tubulin as part of a tyrosination/detyrosination cycle present in most eukaryotic cells. / ttl inhibits spontaneous tubulin polymerization | SIGNOR-176918 |
P18031 | Q13480 | 1 | dephosphorylation | down-regulates activity | 0.38 | Since Gab1 is negatively regulated by PTP1B, a part of the retinal neuroprotective effect we have observed previously in PTP1B deficient mice could be contributed by Gab1 as well.|The results indicate that PTP1B completely dephosphorylated Gab1 and the mutant protein failed to dephosphorylate Gab1 (Figure\u00a0 xref C). | SIGNOR-276965 |
Q9UK99 | Q09472 | 2 | binding | down-regulates quantity by destabilization | 0.341 | O clarify the role of PML in transcription regulation, we purified the PML complex and identified Fbxo3 (Fbx3), Skp1, and Cullin1 as novel components of this complex. Fbx3 formed SCF(Fbx3) ubiquitin ligase and promoted the degradation of HIPK2 and p300 by the ubiquitin-proteasome pathway. | SIGNOR-271742 |
Q6PJ69 | P51668 | 0 | ubiquitination | up-regulates activity | 0.298 | Ubiquitination assays demonstrate that TRIM65 is an ubiquitin E3 ligase for TNRC6 proteins. The combination of overexpression and knockdown studies establishes that TRIM65 relieves miRNA-driven suppression of mRNA expression through ubiquitination and subsequent degradation of TNRC6. TRIM65 regulates ubiquitination and stability of TNRC6. (A) In vitro ubiquitination of TNRC6A by TRIM65 plus E1, E2 (UBCH5A, also known as UBE2D1), ATP, and HA-Ub. GST-tagged TRIM65 and mutant TRIM65 were purified from bacteria. TRIM65 regulates ubiquitination and stability of TNRC6. (A) In vitro ubiquitination of TNRC6A by TRIM65 plus E1, E2 (UBCH5A, also known as UBE2D1), ATP, and HA-Ub. GST-tagged TRIM65 and mutant TRIM65 were purified from bacteria. | SIGNOR-272175 |
P31749 | Q15910 | 1 | phosphorylation | down-regulates activity | 0.594 | Enhancer of zeste homolog 2 (ezh2) is a methyltransferase that plays an important role in many biological processes through its ability to trimethylate lysine 27 in histone h3. Here, we show that akt phosphorylates ezh2 at serine 21 and suppresses its methyltransferase activity by impeding ezh2 binding to histone h3 | SIGNOR-141043 |
O14867 | Q9BYM8 | 0 | ubiquitination | down-regulates quantity by destabilization | 0.345 | HOIL-1 bound Bach1 in vivo and thus stimulated its polyubiquitination in vitro. These results suggest that heme regulates the polyubiquitination of Bach1 and subsequent degradation and that HOIL-1 may function as an E3 ligase in this process. | SIGNOR-236971 |
Q9NR81 | P61586 | 1 | guanine nucleotide exchange factor | up-regulates activity | 0.777 | We therefore developed a screening-compatible live-cell imaging assay, using FRET-based biosensors for the prototype GTPases RHOA, RAC1 and CDC4215,19,20 (Extended Data Fig. 2 and Supplementary Note 1)|We found catalytic activities for 45/75 RhoGEFs and 48/63 RhoGAPs| Our data thus not only reveal extensive promiscuity among regulators, but also that the inactivating RhoGAPs are less selective than the activating RhoGEFs (p-value=0.02)(Supplementary Table 2). | SIGNOR-260530 |
Q9ULW2 | P56706 | 2 | binding | up-regulates | 0.646 | Wnt7b can bind to fzd1 and -10 on the cell surface and cooperatively activate canonical wnt signaling | SIGNOR-137934 |
Q00535 | Q8IV63 | 1 | phosphorylation | up-regulates activity | 0.356 | Vaccinia-related kinase 3 (VRK3), a member of the VRK family, is widely expressed in human tissues and increases VHR phosphatase activity through a direct binding|Here we report that oxidative stress-induced cyclin-dependent kinase 5 (CDK5) activation stimulates neuroprotective signaling via phosphorylation of vaccinia-related kinase 3 (VRK3) at Ser 108. The binding of vaccinia H1-related (VHR) phosphatase to phosphorylated VRK3 increased its affinity for phospho-ERK and subsequently downregulated ERK activation| | SIGNOR-275544 |
Q07955 | O43187 | 0 | phosphorylation | down-regulates activity | 0.348 | IRAK2 phosphorylates SRSF1 and thereby reduces SRSF1 binding to the target mRNAs. | SIGNOR-278406 |
P61586 | Q9P107 | 0 | gtpase-activating protein | down-regulates activity | 0.643 | We therefore developed a screening-compatible live-cell imaging assay, using FRET-based biosensors for the prototype GTPases RHOA, RAC1 and CDC4215,19,20 (Extended Data Fig. 2 and Supplementary Note 1)|We found catalytic activities for 45/75 RhoGEFs and 48/63 RhoGAPs| Our data thus not only reveal extensive promiscuity among regulators, but also that the inactivating RhoGAPs are less selective than the activating RhoGEFs (p-value=0.02)(Supplementary Table 2). | SIGNOR-260505 |
P36894 | Q9HAU4 | 0 | ubiquitination | down-regulates | 0.552 | Smurf1 and smurf2 are e3 ubiquitin ligases known to suppress tgf-beta signaling through degra-dation of smads and receptors for tgf-beta and bmps | SIGNOR-192898 |
Q9C029 | Q86WV6 | 1 | ubiquitination | down-regulates quantity by destabilization | 0.2 | RNF90 promoted K48-linked ubiquitination of MITA and its proteasome-dependent degradation.|Finally, in vitro ubiquitination assays suggested that RNF90 promoted the ubiquitination of MITA directly (Fig 5E and 5F). | SIGNOR-278678 |
P42345 | Q13542 | 1 | phosphorylation | down-regulates | 0.661 | Here, we show that cancer cells acquire resistance to astori by downregulating eukaryotic translation initiation factor (eif4e)-binding proteins (4e-bps-eif4ebp1, eif4ebp2). | SIGNOR-122014 |
O15105 | Q8N5C8 | 2 | binding | up-regulates | 0.382 | The formation of smad7-tab2 and smad7-tab3 complexes resulted in the suppression of tnf signaling. | SIGNOR-153920 |
P25445 | P48023 | 2 | binding | up-regulates activity | 0.903 | The death-inducing receptor fas is activated when cross-linked by the type ii membrane protein faslg (fasl) | SIGNOR-49688 |
Q14493 | Q99880 | 1 | translation regulation | up-regulates quantity by expression | 0.2 | Synthesis of mature histone mRNA requires only a single processing reaction: an endonucleolytic cleavage between a conserved stem-loop and a purine-rich downstream element to form the 3' end. The stem-loop binding protein (SLBP) is required for processing, and following processing, histone mRNA is transported to the cytoplasm, where SLBP participates in translation of the histone mRNA|We used radiolabeled probes generated by PCR targeting the open reading frame (ORF) to detect histones H2A, H2B, H3, H4, and H1 and used 7SK snRNA as a loading control (Fig. 2A). The abundance of histone H2A, H2B, H3, and H4 mRNAs is reduced to 37% to 70% of control levels in the SLBP knockdown cells when compared to the C2 control. | SIGNOR-265389 |
Q14258 | O95786 | 1 | ubiquitination | up-regulates activity | 0.803 | Lys63 linked polyubiquitination of RIG-I at Lys 172 catalyzed by TRIM25 is an important step for RIG-I activation. | SIGNOR-278730 |
P84022 | P29590 | 2 | binding | up-regulates activity | 0.547 | Cytoplasmic pml physically interacts with smad2/3 and sara (smad anchor for receptor activation) and is required for association of smad2/3 with sara and for the accumulation of sara and tgf-beta receptor in the early endosome. | SIGNOR-232090 |
P12931 | Q15306 | 1 | phosphorylation | up-regulates activity | 0.273 | Further, we show here that c-Src dramatically stimulates IRF4 phosphorylation and activity and that Y61 and Y124 are two key sites responding to c-Src-mediated activation.|We have further shown that inhibition of c-Src activity reduces p-IRF4(Y121/124) and significantly represses transcription of the IRF4 target B cell integration cluster in Epstein-Barr virus-transformed cells. | SIGNOR-279287 |
O75925 | P68400 | 0 | phosphorylation | up-regulates | 0.332 | Ck2 phosphorylates serine residues adjacent to the sim of pias1 these findings show that the phosphosim module mediates binding to free sumo and sumo conjugates in a phosphorylation-dependent mode, with ck2 being the critical kinase involvedin this process. | SIGNOR-184047 |
P15884 | Q02535 | 2 | binding | down-regulates activity | 0.458 | All three Ids bound with high affinity to E proteins .Each Id was able to disrupt the ability of E protein-MyoD complexes to transactivate from a muscle creatine kinase reporter construct in vivo. | SIGNOR-241379 |
Q05655 | Q9UQ80 | 1 | phosphorylation | up-regulates | 0.509 | Trk receptor activation by both ngf and bdnf induced phosphorylation of ebp1 at the s360 upon the activation of protein kinase c (pkc ) and triggered dissociation of p48 from retinoblastoma (rb | SIGNOR-170348 |
P61586 | P36544 | 2 | binding | up-regulates activity | 0.2 | Here, we demonstrate a role for α7 nAChR/G protein interaction in the activation of the small (monomeric) RhoA GTPase leading to cytoskeletal changes during neurite growth. Treatment of PC12 cells with the α7 nAChR agonist choline or PNU-282987 was associated with an increase in RhoA activity and an inhibition in neurite growth. | SIGNOR-253985 |
Q9UD71 | Q00535 | 0 | phosphorylation | up-regulates activity | 0.777 | We find that DARPP-32 is converted into an inhibitor of PKA when phosphorylated at threonine 75 by cyclin-dependent kinase 5 (Cdk5). Cdk5 phosphorylates DARPP-32 in vitro and in intact brain cells. Phospho-Thr 75 DARPP-32 inhibits PKA in vitro by a competitive mechanism. | SIGNOR-250671 |
P60953 | Q96PX9 | 0 | guanine nucleotide exchange factor | up-regulates activity | 0.285 | We therefore developed a screening-compatible live-cell imaging assay, using FRET-based biosensors for the prototype GTPases RHOA, RAC1 and CDC4215,19,20 (Extended Data Fig. 2 and Supplementary Note 1)|We found catalytic activities for 45/75 RhoGEFs and 48/63 RhoGAPs| Our data thus not only reveal extensive promiscuity among regulators, but also that the inactivating RhoGAPs are less selective than the activating RhoGEFs (p-value=0.02)(Supplementary Table 2). | SIGNOR-260565 |
P04626 | P23470 | 0 | dephosphorylation | up-regulates activity | 0.289 | 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-254701 |
P52945 | Q13043 | 0 | phosphorylation | down-regulates activity | 0.2 | MST1 directly phosphorylated PDX1 at Thr11, resulting in its ubiquitination, degradation and impaired insulin secretion.|Thus, kinase activity is required for MST1 induced PDX1 degradation. | SIGNOR-278303 |
P04049 | P04049 | 2 | phosphorylation | up-regulates activity | 0.2 | We show that phosphorylation of s621 turns over rapidly and is enriched in the activated pool of endogenous raf-1. The phosphorylation on this site can be mediated by raf-1 itself but also by other kinase(s) | SIGNOR-235770 |
O43639 | P00533 | 2 | binding | up-regulates | 0.399 | Growth factor binding to receptor protein tyrosine kinases (r-ptks)1 induces their dimerization and trans-phosphorylation, creating docking sites for proteins containing sh2 and ptb protein interaction domains. Nck binds to the pdgf and egfr receptors (figure 3c). | SIGNOR-64731 |
Q9HAT8 | Q96P20 | 1 | ubiquitination | up-regulates activity | 0.2 | Pellino2 promotes ubiquitination of NLRP3.|We now demonstrate that Pellino2 can promote increased production of mature bioactive IL-1beta by facilitating activation of the NLRP3 inflammasome. | SIGNOR-278525 |
P07947 | P07355 | 1 | phosphorylation | up-regulates activity | 0.2 | Activated YES1 interacts with ANXA2 andphosphorylates ANXA2 at Tyr24 site that induces ANXA2 activation and increases ANXA2 nuclear distribution , leading to activation of the tumorpromoting transcription factors ( such as Myc , Stat3 , Stat6 ) that promotes GC invasion and metastasis .|YES1 phosphorylates ANXA2 at Tyr24 site that leads to ANXA2 activation and increased ANXA2 nuclear distribution. | SIGNOR-279435 |
Q9NX47 | O00429 | 1 | polyubiquitination | down-regulates quantity by destabilization | 0.2 | We found that MITOL associated with and ubiquitinated mitochondrial fission protein hFis1 and Drp1.Pulse–chase experiment also indicated that MITOL overexpression promoted Drp1 turnover. | SIGNOR-271894 |
P50549 | Q13535 | 0 | phosphorylation | up-regulates quantity by stabilization | 0.2 | Collectively, the results described above indicate that ATR phosphorylates ETV1 and stabilizes it from proteolytic degradation. | SIGNOR-279355 |
P42658 | Q9NZV8 | 1 | relocalization | up-regulates activity | 0.548 | DPPX-S reduced energy barriers of the voltage-dependent transitions; therefore, this auxiliary subunit may exert a catalytic effect on voltage-dependent gating of Kv4.2 channels. DPPX-S may also accelerate coupled inactivation indirectly | SIGNOR-269005 |
P00533 | P06493 | 0 | phosphorylation | down-regulates | 0.426 | Using a synthetic peptide corresponding to the sequence surrounding ser-1002, p34cdc2 was identified as a kinase capable of phosphorylating this serine residue. phosphorylation of the egf receptor by p34cdc2 was associated with a decrease in its tyrosine protein kinase activity. | SIGNOR-38313 |
P36956 | P49336 | 0 | phosphorylation | up-regulates activity | 0.474 | Biochemical analyses reveal that SREBP-1c can be directly phosphorylated by CDK8 at the conserved Threonine-402 residue (T402) in vitro and in cultured mammalian cells ( xref ).|Therefore, the mechanism of CDK8 regulating SREBP functions is primarily through the phosphorylation initiated control of nuclear SREBP-1 protein stability. | SIGNOR-279688 |
P24385 | P01106 | 0 | transcriptional regulation | up-regulates quantity by expression | 0.496 | C-myc directly activates transcription of cyclin d1, cyclin d2 and cdk4, and leads to cdk 4/6 activation | SIGNOR-102731 |
P27361 | P78347 | 1 | phosphorylation | up-regulates | 0.374 | Tfii-i can be phosphorylated in vitro by erk and mutation of consensus map kinase substrate sites at serines 627 and 633 impairs the phosphorylation of tfii-i by erk and its activity on the c-fos promoter. These results suggest that erk regulates the activity of tfii-i by direct phosphorylation. | SIGNOR-74308 |
Q15744 | P53567 | 2 | binding | up-regulates activity | 0.373 | C/EBP-epsilon interacts with C/EBP-gamma through the leucine-zipper containing domain. C/EBP-epsilon and C/EBP-gamma synergistically activate transcription of lactoferrin promoter | SIGNOR-224900 |
P04201 | P01019-PRO_0000420660 | 2 | binding | up-regulates activity | 0.2 | Recent advances have improved our understanding of the renin-angiotensin system (RAS). These have included the recognition that angiotensin (Ang)-(1-7) is a biologically active product of the RAS cascade. The identification of the ACE homologue ACE2, which forms Ang-(1-7) from Ang II, and the GPCR Mas as an Ang-(1-7) receptor have provided the necessary biochemical and molecular background and tools to study the biological significance of Ang-(1-7). | SIGNOR-260229 |
P30566 | Q96KS0 | 0 | hydroxylation | up-regulates activity | 0.2 | ADSL is hydroxylated by EglN2 on Proline 24. An integrated transcriptomics and metabolomics analysis reveals that ADSL activates the oncogenic cMYC pathway by regulating cMYC protein level via a mechanism requiring ADSL proline 24 hydroxylation. ADSL regulates cMYC protein level through adenosine levels | SIGNOR-266613 |
Q92544 | P42345 | 2 | binding | down-regulates activity | 0.2 | TM9SF4 inhibited mTOR activity in HEK293 cells. Under nutrient starvation, TM9SF4 functions to facilitate mTOR inactivation, resulting in an enhanced autophagic flux, which serves to protect cells from apoptotic cell death. | SIGNOR-266703 |
Q9NX47 | Q9Y3D6 | 1 | ubiquitination | down-regulates quantity by destabilization | 0.2 | MITOL associates with and ubiquitinates mitochondrial fission protein hFis1. (A) Ubiquitination of hFis1 by MITOL. Thus, MITOL may control the protein expression level of hFis1 through the ubiquitin–proteasome pathway. | SIGNOR-274141 |
P63151 | P01137 | 2 | binding | up-regulates activity | 0.385 | The Balpha subunit interacts directly with activated T_RI. The Balpha interaction with the receptor is expected to result in enhanced protein phosphatase 2A activity | SIGNOR-217894 |
O00560 | Q06945 | 2 | binding | up-regulates activity | 0.538 | Sox4 activation by IL-5R_ appears to be direct, with syntenin functioning as an adaptor molecule. Syntenin mediates IL-5induced Sox4 activation. | SIGNOR-223089 |
Q9HAU4 | Q99717 | 1 | ubiquitination | down-regulates | 0.736 | Smurf1 and smurf2 are e3 ubiquitin ligases known to suppress tgf-beta signaling through degra-dation of smads and receptors for tgf-beta and bmps | SIGNOR-193378 |
P60568 | P14784 | 2 | binding | up-regulates | 0.869 | Il-2 is a cytokine that functions as a growth factor and central regulator in the immune system and mediates its effects through ligand-induced hetero-trimerization of the receptor subunits il-2r alpha, il-2r beta, and gamma(c). | SIGNOR-144540 |
O15162 | Q05655 | 0 | phosphorylation | up-regulates | 0.424 | Following the induction of apoptosis, however, phosphorylation of serine residues decreased and it increased on threonine, consistent with the predicted pkc phosphorylation site at thr-161. Transfection of cho cells with scramblase and pkc_, but not scramblase or pkc_ alone, increased scramblase activity | SIGNOR-76904 |
Q96GD4 | P54274 | 1 | phosphorylation | up-regulates activity | 0.366 | Our data indicate that AURKB can phosphorylate the integral telomere DNA-binding Shelterin protein TERF1 at S404 (within the DNA-binding domain) in vitro . | SIGNOR-279440 |
P10275 | Q9Y4D8 | 0 | ubiquitination | down-regulates quantity by destabilization | 0.2 | We identified several E3 ligases as strong candidates responsible for AR and MYC protein loss as HECTD4, MYCBP2, and TRIM49. HECTD4 and MYCBP2 target AR and MYC for degradation while TRIM49 appears to promote AR and MYC stability. We have shown that these E3 ligases in turn are directly regulated by MYC. MYC in turn represses the expression of ubiquitin ligases, HECTD4 and MYCBP2 that promote AR and MYC protein degradation, further suppressing MYC and AR in a feed forward loop. | SIGNOR-267148 |
O00254 | Q03113 | 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-257409 |
Q96PY5 | P06493 | 0 | phosphorylation | up-regulates activity | 0.2 | In this study we have identified the formin FMNL2 as a novel substrate for CDK1 that plays a role in maintaining adhesion complexes and facilitates cell cycle–dependent changes in adhesion complexes. Knockdown of FMNL2 or expression of a nonphosphorylatable S1016A mutant resulted in the loss of adhesion complexes and stress fibers within the cell body, with peripheral structures being maintained. | SIGNOR-273555 |
P84243 | P17612 | 0 | phosphorylation | up-regulates activity | 0.2 | Identification of a novel phosphorylation site on histone h3 coupled with mitotic chromosome condensation. | SIGNOR-70424 |
O43426 | P29323 | 0 | phosphorylation | down-regulates | 0.57 | Ephb2 causes tyrosine phosphorylation in the proline-rich domain of synaptojanin 1, and inhibits both the interaction with endophilin and the 5'-phosphatase activity of synaptojanin 1 | SIGNOR-135274 |
P24941 | O14757 | 1 | phosphorylation | up-regulates | 0.554 | Chk1 itself is also subject to cdk-mediated phosphorylation at serines 286 and 301 (s286 and 301). We show that chk1 s301 phosphorylation increases as cells progress through s and g2 and that both cdk1 and cdk2 are likely to contribute to this modification in vivo. We also find that substitution of s286 and s301 with non-phosphorylatable alanine residues strongly attenuates dna damage-induced chk1 activation and g2 checkpoint proficiency | SIGNOR-175083 |
O14641 | Q9Y2G4 | 2 | binding | up-regulates | 0.473 | Our data thus demonstrate that diversin and dishevelled function together in a mutually dependent fashion in zebrafish gastrulation and organ formation | SIGNOR-162142 |
P35222 | P15172 | 2 | binding | up-regulates activity | 0.406 | Together, these results suggest that B-Cat increases MyoD binding to E box elements | SIGNOR-255653 |
P15498 | P50570 | 2 | binding | up-regulates quantity by stabilization | 0.488 | Disruption of the Dyn2-Vav1 interaction targets Vav1 to the lysosome for degradation via an interaction with the cytoplasmic chaperone Hsc70, resulting in a dramatic reduction of Vav1 protein stability. | SIGNOR-259080 |
Q13635 | P14635 | 2 | binding | up-regulates | 0.684 | In addition, we demonstrate that endogenous ptc1 and endogenous cyclin B1 interact in vivo. The findings reported here demonstrate that ptc1 participates in determining the subcellular localization of cyclin B1 and suggest a link between the tumor suppressor activity of ptc1 and the regulation of cell division. Thus, we propose that ptc1 participates in a G2/M checkpoint by regulating the localization of MPF. | SIGNOR-199147 |
P51681 | P13501 | 2 | binding | up-regulates activity | 0.937 | CCL5, also known RANTES (regulated on activation, normal T cell expressed and secreted), is a potent chemoattractant for a variety of leukocytes, including T cells, mono- cytes, NK cells, and basophils, signaling via the CCR1, CCR3, and CCR5 cell surface receptors [59]. Among these receptors, CCL5 has the highest affinity for CCR5. | SIGNOR-277726 |
P36873 | Q9BYX4 | 1 | dephosphorylation | up-regulates activity | 0.247 | Exogenous PP1alpha or PP1gamma substantially decreased the S88 phosphorylation of Flag-MDA5|we identified PP1alpha and PP1gamma as primary phosphatases responsible for MDA5 and RIG-I dephosphorylation, leading to their activation. | SIGNOR-264579 |
Q07954 | P00734 | 2 | binding | up-regulates | 0.282 | In vitro binding studies revealed that antithrombin iii (atiii)thrombin, heparin cofactor ii (hcii)thrombin, and ?1-antitrypsin (?1AT)trypsin bound to purified lrp | SIGNOR-41090 |
P61586 | Q8N103 | 0 | gtpase-activating protein | down-regulates activity | 0.447 | We therefore developed a screening-compatible live-cell imaging assay, using FRET-based biosensors for the prototype GTPases RHOA, RAC1 and CDC4215,19,20 (Extended Data Fig. 2 and Supplementary Note 1)|We found catalytic activities for 45/75 RhoGEFs and 48/63 RhoGAPs| Our data thus not only reveal extensive promiscuity among regulators, but also that the inactivating RhoGAPs are less selective than the activating RhoGEFs (p-value=0.02)(Supplementary Table 2). | SIGNOR-260523 |
P02511 | P07320 | 2 | binding | up-regulates activity | 0.52 | Human gamma-crystallins are long-lived, unusually stable proteins of the eye lens exhibiting duplicated, double Greek key domains. The lens also contains high concentrations of the small heat shock chaperone alpha-crystallin, which suppresses aggregation of model substrates in vitro. Mature-onset cataract is believed to represent an aggregated state of partially unfolded and covalently damaged crystallins. The alphaB-crystallin oligomers formed long-lived stable complexes with their gammaD-crystallin substrates. These in vitro results provide support for protein unfolding/protein aggregation models for cataract, with alpha-crystallin suppressing aggregation of damaged or unfolded proteins through early adulthood but becoming saturated with advancing age. | SIGNOR-253621 |
P36956 | Q8NBP7 | 1 | transcriptional regulation | up-regulates quantity by expression | 0.427 | Expression of nuclear forms of sterol-regulatory element binding protein-1 (SREBP-1) and SREBP-2 dramatically increased the promoter activity of PCSK9. | SIGNOR-255222 |
P05198 | Q9Y6E2 | 2 | binding | up-regulates activity | 0.253 | BZW2, as an evolutionary highly conserved protein, interacts with eIF2 and eIF3 and promotes ternary complex formation in vitro | SIGNOR-261220 |
Q00535 | Q16643 | 1 | phosphorylation | up-regulates activity | 0.539 | Phosphorylation of drebrin at S142 by Cdk5 relieves the intramolecular inhibition of F-actin bundling. | SIGNOR-279452 |
Q99755 | Q92997 | 2 | binding | up-regulates | 0.2 | Wnt3a stimulates the formation of phosphatidylinositol 4,5-bisphosphates [ptdins (4,5)p2] through frizzled and dishevelled, the latter of which directly interacted with and activated pip5ki. | SIGNOR-180788 |
P15918 | P42345 | 1 | relocalization | up-regulates | 0.256 | Rag gtpases, together with a multi-protein complex called ragulator, mediate amino acid-mediated mtor recruitment to the lysosome surface where mtor becomes activated. | SIGNOR-198242 |
Q8N6P7 | Q9NYY1 | 2 | binding | up-regulates | 0.606 | An IL-20 receptor was identified as a heterodimer of two orphan class II cytokine receptor subunits. Both receptor subunits are expressed in skin and are dramatically upregulated in psoriatic skin. Taken together, these results demonstrate a role in epidermal function and psoriasis for IL-20, a novel cytokine identified solely by bioinformatics analysis. | SIGNOR-151877 |
P35611 | Q00535 | 0 | phosphorylation | up-regulates activity | 0.255 | We found that Cdk5 directly phosphorylated the actin-binding protein adducin-1 (ADD1) at T724 in vitro and in intact cells. | SIGNOR-277487 |
Q9UIF8 | Q16695 | 2 | binding | down-regulates activity | 0.2 | The BAZ2B bromodomain has been shown to bind to acetylated H3K14 (H3K14ac), whose presence at promoter regions is generally associated with gene activation. This suggests a potential role for BAZ2B in transcriptional activation. | SIGNOR-266620 |
P49023 | Q14289 | 0 | phosphorylation | down-regulates quantity by destabilization | 0.94 | P130Cas and paxillin can be phosphorylated by Fak or Pyk2, and bind directly to these kinases. | SIGNOR-279272 |
Q8WU20 | P21802 | 0 | phosphorylation | up-regulates activity | 0.777 | In this report, we demonstrate that FGF stimulation induces tyrosine phosphorylation of a novel lipid anchored docking protein, termed FRS2, that forms a complex with Grb2/Sos, thus linking FGF-receptor activation to the Ras/MAPK signaling pathway. | SIGNOR-236950 |
Q9NRM7 | Q14872 | 1 | phosphorylation | down-regulates activity | 0.2 | The Hippo pathway kinases LATS1 and LATS2 attenuate cellular responses to heavy metals through phosphorylating MTF1|the Hippo pathway kinase LATS phosphorylates and inhibits MTF1|LATS phosphorylates MTF1 at S152 and disrupts its association with the promoters of heavy metal response genes, resulting in the loss of heavy metal response gene expression | SIGNOR-275475 |
O95863 | P49841 | 0 | phosphorylation | down-regulates | 0.557 | Snail is a well-known zn-finger transcription factor that promotes emt by repressing e-cadherin expression. It is known that snail is phosphorylated by gsk3beta and degraded by beta-trcp-mediated ubiquitination. A variant of snail (snail-6sa), which abolishes these phosphorylations, is much more stable and resides exclusively in the nucleus to induce emt | SIGNOR-129402 |
P18031 | P12931 | 1 | dephosphorylation | up-regulates activity | 0.781 | Incubation of the inactivated c-Src with PTP1B results in a dose-dependent reactivation of c-Src tyrosine kinase activity. Incubation of c-Src with 2 or 10 g of PTP1B results in partial or full restoration of c-Src kinase activity, respectively. The activation is accompanied by dephosphorylation of c-Src, both of Tyr-419 and of Tyr-530 | SIGNOR-245299 |
Q5TEC6 | Q14493 | 0 | translation regulation | up-regulates quantity by expression | 0.2 | Synthesis of mature histone mRNA requires only a single processing reaction: an endonucleolytic cleavage between a conserved stem-loop and a purine-rich downstream element to form the 3' end. The stem-loop binding protein (SLBP) is required for processing, and following processing, histone mRNA is transported to the cytoplasm, where SLBP participates in translation of the histone mRNA|We used radiolabeled probes generated by PCR targeting the open reading frame (ORF) to detect histones H2A, H2B, H3, H4, and H1 and used 7SK snRNA as a loading control (Fig. 2A). The abundance of histone H2A, H2B, H3, and H4 mRNAs is reduced to 37% to 70% of control levels in the SLBP knockdown cells when compared to the C2 control. | SIGNOR-265415 |
P17612 | P13224 | 1 | 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 |
Q14980 | Q9NY65 | 2 | binding | up-regulates | 0.2 | Direct binding of numa to tubulin is mediated by a novel sequence motif in the tail domain that bundles and stabilizes microtubules. | SIGNOR-116826 |
P46531 | Q9P2R6 | 2 | binding | up-regulates activity | 0.318 | In mammalian cells, RERE co‐immunoprecipitates with CBF1 and Notch intracellular domain (NICD), and is recruited to nuclear foci formed by over‐expressed NICD1. RERE is also necessary for NICD to activate the expression of Notch target genes. | SIGNOR-264486 |
P15172 | Q6STE5 | 2 | binding | up-regulates | 0.538 | This suggests a novel mechanism by which myod interacts with the promoter indirectly via pbx-1 and recruits chromatin-remodeling enzymes, which then facilitate the binding of myod and other regulators. Demonstration of physical interactions between brg1 and myod and brg1 and pbx support this conclusion | SIGNOR-136130 |
Q92696 | P20336 | 1 | lipidation | up-regulates activity | 0.569 | Prenylation (or geranylgeranylation) of Rab GTPases is catalysed by RGGT (Rab geranylgeranyl transferase) and requires REP (Rab escort protein). In the classical pathway, REP associates first with unprenylated Rab, which is then prenylated by RGGT. In the alternative pathway, REP associates first with RGGT; this complex then binds and prenylates Rab proteins. Rab GTPases need to be geranylgeranylated on either one or two cysteine residues in their Ctermini in order to localize to the correct intracellular membrane and be functional | SIGNOR-265574 |
Q9H4A3 | P55011 | 1 | phosphorylation | up-regulates activity | 0.491 | Combining these biochemical studies with the live cell imaging data, these results collectively suggest that the entire CTD is necessary for WNK1 to drive optimal SPAK/OSR1 activation and downstream NKCC1/KCC phosphorylation via PS. | SIGNOR-277859 |
O00170 | P04155 | 1 | transcriptional regulation | down-regulates quantity by repression | 0.2 | We show that XAP2 is recruited to the promoter of ERα regulated genes like the breast cancer marker gene pS2 or GREB1 and negatively regulate the expression of these genes in MCF-7 cells. | SIGNOR-259911 |
Q8WXG6 | Q8TDJ6 | 2 | binding | up-regulates quantity | 0.448 | We isolated here a novel protein that was co-immunoprecipitated with Rab3 GEP and GAP by their respective antibodies from the crude synaptic vesicle fraction of rat brain. The protein, named rabconnectin-3, bound both Rab3 GEP and GAP. These results indicate that rabconnectin-3 serves as a scaffold molecule for both Rab3 GEP and GAP on synaptic vesicles. | SIGNOR-265581 |
P06493 | P29590 | 1 | phosphorylation | down-regulates | 0.345 | Here, we show that klhl20, a cullin3 (cul3) substrate adaptor induced by hif-1, coordinates with the actions of cdk1/2 and pin1 to mediate hypoxia-induced pml proteasomal degradation. | SIGNOR-176033 |
P35222 | Q15139 | 0 | phosphorylation | up-regulates | 0.388 | This study provides evidence that pkd1 interacts with and phosphorylates beta-catenin at thr(112) and thr(120) we postulate that pkd1 phosphorylation is required to maintain _-catenin transcription activity. | SIGNOR-183384 |
P15172 | Q02078 | 2 | binding | up-regulates activity | 0.742 | Myod-e protein heterodimers interact with mef2 proteins to synergistically activate myogenesis. | SIGNOR-54086 |
P07900 | Q8TF40 | 2 | binding | down-regulates activity | 0.547 | 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-261413 |
Q9UJT9 | Q96ME1 | 2 | binding | down-regulates quantity by destabilization | 0.652 | F-box protein Fbxl18 mediates polyubiquitylation and proteasomal degradation of the pro-apoptotic SCF subunit Fbxl7.. Here, we identified that an orphan F-box protein, Fbxl18, targets Fbxl7 for its polyubiquitylation and proteasomal degradation. Lys 109 within Fbxl7 is an essential acceptor site for ubiquitin conjugation by Fbxl18. | SIGNOR-272448 |
P05198 | Q92879 | 2 | binding | up-regulates activity | 0.251 | These studies showed that both the increased levels of CUGBP1 and cdk4-mediated hyper-phosphorylation of CUGBP1 are involved in the age-associated induction of the CUGBP1-eIF2 complex. The CUGBP1-eIF2 complex is bound to C/EBPbeta mRNA in the liver of old animals, and this binding correlates with the increased amounts of liver-enriched activator protein and liver-enriched inhibitory protein. | SIGNOR-262736 |
Q05513 | Q8TEW0 | 1 | phosphorylation | up-regulates | 0.711 | These results imply that serine 827 in the apkc binding site of par-3 is a target of apkc and that the regulated interaction between a protein kinase, apkc, and its substrate, par-3, plays an essential role in the establishment of cell polarity | SIGNOR-94523 |
Q07820 | P06493 | 0 | phosphorylation | down-regulates quantity by destabilization | 0.461 | Mcl-1 is phosphorylated at two sites in mitosis, ser64 and thr92. Phosphorylation of thr92 by cyclin-dependent kinase 1 (cdk1)-cyclin b1 initiates degradation of mcl-1 in cells arrested in mitosis by microtubule poisons. | SIGNOR-165867 |
P63096 | P29274 | 2 | binding | up-regulates activity | 0.273 | 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-257038 |
Q13635 | Q14623 | 2 | binding | down-regulates activity | 0.838 | Biochemical analysis of ptch and ptch2 shows that they both bind to all hedgehog family members with similar affinity and that they can form a complex with smo.Current models suggest that binding of Shh to PTCH prevents the normal inhibition of the seven-transmembrane-protein Smoothened (SMO) by PTCH. | SIGNOR-61311 |
P48454 | Q92934 | 1 | dephosphorylation | up-regulates activity | 0.399 | Ca2+-induced apoptosis through calcineurin dephosphorylation of BAD|Calcineurin was found to dephosphorylate BAD, a pro-apoptotic member of the Bcl-2 family, thus enhancing BAD heterodimerization with Bcl-xL and promoting apoptosis. | SIGNOR-248529 |
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