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 |
|---|---|---|---|---|---|---|---|
Q96N96 | Q96SB3 | 2 | binding | up-regulates activity | 0.481 | Here we show that Asef2, but not Asef, interacts with Neurabin2/Spinophilin, a scaffold protein that binds to Filamentous actin (F-actin). Neurabin2 is required for Asef2-induced filopodia formation. RNA interference experiments showed that Asef2, Neurabin2 and APC are involved in HGF-induced cell migration. Furthermore, knockdown of Neurabin2 resulted in the suppression of Asef2-induced filopodia formation. | SIGNOR-269174 |
P01019-PRO_0000032458 | P12821 | 0 | cleavage | up-regulates quantity | 0.2 | Ang I is subsequently converted into the major RAS effector peptide Ang II or Ang (1–8), through activity of the zinc-dependent protease ACE, which hydrolyzes two amino acids from the carboxy terminus of Ang I | SIGNOR-260236 |
P24941 | P48431 | 1 | phosphorylation | up-regulates activity | 0.394 | Cdk2 physically interacts with Sox2 and phosphorylates Sox2 at Ser 39 and Ser 253 in vitro. | SIGNOR-279448 |
Q8TCU6 | Q8WXX7 | 2 | binding | up-regulates activity | 0.252 | Mutations in the Autism susceptibility candidate 2 gene (AUTS2), whose protein is believed to act in neuronal cell nuclei, have been associated with multiple psychiatric illnesses, including autism spectrum disorders, intellectual disability, and schizophrenia. Here we show that cytoplasmic AUTS2 is involved in the regulation of the cytoskeleton and neural development. AUTS2 activates Rac1 to induce lamellipodia but downregulates Cdc42 to suppress filopodia. Our loss-of-function and rescue experiments show that a cytoplasmic AUTS2-Rac1 pathway is involved in cortical neuronal migration and neuritogenesis in the developing brain. These results suggest that FL-AUTS2 can activate Rac1 via interaction with P-Rex1 and the Elmo2/Dock180 complex to regulate actin dynamics in N1E-115 cells. | SIGNOR-266817 |
Q13489 | Q6GPH4 | 2 | binding | down-regulates | 0.391 | Immunoprecipitation studies indicate that xaf1 binds to xiap,birc2,birc3 | SIGNOR-155288 |
O14842 | P63096 | 2 | binding | up-regulates activity | 0.307 | 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-257071 |
P11362 | Q14247 | 1 | phosphorylation | down-regulates | 0.313 | Cortactin, which is an actin-binding protein that also plays a role in actin cytoskeleton dynamics (45), was phosphorylated on tyr-446 in our assay (by fgfr1).Phosphorylation of these residues attenuates the f-actin cross-linking activity | SIGNOR-98618 |
Q9P0W2 | O15344 | 0 | polyubiquitination | down-regulates quantity by destabilization | 0.244 | The E3 ubiquitin ligase MID1/TRIM18 promotes atypical ubiquitination of the BRCA2-associated factor 35, BRAF35. MID1 is implicated in BRAF35 ubiquitination promoting atypical poly-ubiquitination via K6-, K27- and K29-linkages. We found that MID1 depletion alters BRAF35 localization in these structures and increases BRAF35 stability affecting its cytoplasmic abundance | SIGNOR-272317 |
P02746 | Q07021 | 2 | binding | down-regulates activity | 0.341 | Previous studies have shown that gC1qR inhibits aggregated IgG-mediated complement activation by binding to the gC1q site on C1q, thereby preventing IgG from binding to the gh’s (28), suggesting that the binding sites for gC1qR and IgG on C1q may be identical or at least overlapping. | SIGNOR-263403 |
O95837 | P30874 | 2 | binding | up-regulates activity | 0.353 | 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-256963 |
Q01094 | Q86T82 | 1 | transcriptional regulation | up-regulates quantity by expression | 0.2 | USP37 was induced by E2F transcription factors in G1|Ectopic E2F1 activated the wild-type promoter, but not the mutant promoter, 3-fold over basal levels in 293T cells (Figure 4F), confirming the functionality of the E2F binding sites in the USP37 promoter. | SIGNOR-265047 |
P29274 | P38405 | 2 | binding | up-regulates activity | 0.315 | 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-256909 |
P49023 | Q13882 | 0 | phosphorylation | up-regulates activity | 0.63 | It was also observed that the attenuation of BRK phosphorylation in turn inhibits BRK mediated activation of its direct targets, STAT3, SAM68, and Paxillin.|The EGF pathway also stimulates BRK 's phosphorylation of paxillin to promote migratory and invasive characteristics in breast cancer cells. | SIGNOR-280102 |
P23458 | Q9NZJ5 | 1 | phosphorylation | up-regulates activity | 0.2 | JAK1 interacts with and phosphorylates PERK. PERK-dependent activation of JAK1 and STAT3 contributes to endoplasmic reticulum stress-induced inflammation. Similarly, PERK is associated with and phosphorylated by JAK1 at Y585 and Y619 (and possibly other JAKs) during ER stress, resulting in PERK- and JAK1-dependent activation of STAT3. | SIGNOR-276677 |
P29350 | Q13237 | 0 | phosphorylation | up-regulates activity | 0.2 | PKGII directly phosphorylated and stimulated SHP-1 activity | SIGNOR-276288 |
Q8TDV5 | P63092 | 2 | binding | up-regulates activity | 0.414 | 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 ‚â• -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 ‚â• -1.0 for defining true couplings. | The score associated to this interaction has a LogRAi ‚â• -1.0. | SIGNOR-256768 |
P05129 | Q99418 | 1 | phosphorylation | down-regulates activity | 0.332 | ARNO is phosphorylated in vivo by PKC on a single serine residue, S392, located within the carboxy-terminal polybasic domain. Mutation of S392 to alanine does not prevent ARNO-mediated actin rearrangements, suggesting that phosphorylation does not lead to ARNO activation [6]. Here, we report that phosphorylation negatively regulates ARNO exchange activity through a 'PH domain electrostatic switch'. | SIGNOR-249025 |
P12931 | O15259 | 1 | phosphorylation | up-regulates activity | 0.297 | Src-induced tyrosine phosphorylation could be prevented by mutating the tyrosine residue at position 721 to phenylalanine ( C, lane 12) suggesting that Src kinase phosphorylates NPHP1 at tyrosine 721. | SIGNOR-279122 |
P04062 | P19484 | 0 | transcriptional regulation | up-regulates quantity by expression | 0.325 | Nucleus-Translocated ACSS2 Promotes Gene Transcription for Lysosomal Biogenesis and Autophagy|A chromatin immunoprecipitation (ChIP) assay with antibodies against TFEB or ACSS2 demonstrated that glucose deprivation results in the binding of TFEB (Figure 3D) and ACSS2 (Figure 3E) to the promoter regions of CTSA, GBA, GUSB, and LAMP1|These results indicated that TFEB and ACSS2 are mutually required for their binding to the promoter regions of lysosomal genes. In line with these findings, glucose deprivation induced mRNA (Figure 3F) and protein (Figure 3G) expression for these lysosomal genes, which was largely abrogated by knockin of ACSS2 mutants | SIGNOR-276551 |
P00519 | Q14847 | 1 | phosphorylation | up-regulates | 0.343 | C-abl activation by apoptotic agents specifically promotes phosphorylation of lasp-1 at tyrosine 171, which is associated with the loss of lasp-1 localization to focal adhesions and induction of cell death. Thus, lasp-1 is a dynamic focal adhesion protein necessary for cell migration and survival in response to growth factors and ecm proteins. | SIGNOR-124719 |
P28702 | P24468 | 2 | binding | up-regulates | 0.275 | Arp-1/rxr, coup-tfi/rxr, and arp-1/coup-tfi heterodimers bound the fp330-3' site. | SIGNOR-79452 |
Q9NZ94 | Q9HDB5 | 2 | binding | up-regulates activity | 0.825 | Pre- and postsynaptic plasma membranes are always precisely aligned, and are separated by a synaptic cleft of ~20 nm. The cleft contains an undefined proteinaceous material in the middle, and is presumably bridged by synaptic cell-adhesion molecules such as Nrxns and Nlgns that align the pre- and postsynaptic elements and mediate trans-synaptic signaling.|Nlgns bind to both alpha- and beta-Nrxns with nanomolar affinities; binding involves the sixth LNS-domain of alpha-Nrxns which corresponds to the only LNS-domain of beta-Nrxns52. The binding affinities differ characteristically between various pairs of Nlgns and Nrxns, and are controlled by alternative splicing of both Nrxns and Nlgns (Figure 1c) | SIGNOR-264167 |
Q00987 | P08069 | 1 | ubiquitination | down-regulates quantity by destabilization | 0.66 | We could prove that Mdm2 physically associates with IGF-1R and that Mdm2 causes IGF-1R ubiquitination in an in vitro assay. | SIGNOR-278571 |
Q96A00 | P17252 | 0 | phosphorylation | up-regulates activity | 0.523 | 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-249259 |
Q96PH1 | Q9UQM7 | 0 | phosphorylation | up-regulates activity | 0.2 | In vitro phosphorylation assays revealed that CAMKII can directly phosphorylate Nox5 on Thr494 and Ser498 as detected by phosphorylation state-specific antibodies. Mass spectrometry (MS) analysis revealed the phosphorylation of additional, novel sites at Ser475, Ser502, and Ser675. Of these phosphorylation sites, mutation of only Ser475 to alanine prevented CAMKII-induced increases in Nox5 activity. Together, these results suggest that CAMKII can positively regulate Nox5 activity via the phosphorylation of Ser475. | SIGNOR-276329 |
Q01974 | Q01974 | 2 | binding | up-regulates | 0.2 | Wnt5a induces homodimerization and activation of ror2 receptor tyrosine kinase | SIGNOR-199588 |
Q15262 | Q9ULT6 | 1 | dephosphorylation | up-regulates activity | 0.354 | We show that PTPRK acts via the transmembrane E3 ubiquitin ligase ZNRF3, a negative regulator of Wnt signaling promoting Wnt receptor degradation, which is also expressed in the organizer. | SIGNOR-260110 |
O60260 | P68036 | 0 | ubiquitination | up-regulates activity | 0.2 | Only UbcH5 and Related Class I E2s Support Ubiquitination of S5a—UbcH5 belongs to the Class I family of E2s which contains a catalytic core (UBC domain) without a distinct Ub binding domain (38). To test whether other Class I E2s can also support ubiquitination of S5a, we assayed the ubiquitination of S5a with UbcH7 and the E3s, Nedd4, or Parkin. With either of these E3s, UbcH7 supported ubiquitination of S5a (Fig. 8, A and B). In addition, another Class I E2, Ubc4, a close homolog of UbcH5, supported ubiquitination of S5a by the APC, a multimeric Ring finger E3 responsible for cell cycle progression through mitosis (39) (Fig. 8C). Thus, multiple Class I E2s can support ubiquitination of S5a by various types of E3s (Table 1). | SIGNOR-272734 |
Q7Z2W7 | P17612 | 0 | phosphorylation | up-regulates activity | 0.2 | Using specific pharmacological and molecular tools combined with patch-clamp current recordings, we found that in heterologously expressed HEK-293 (human embryonic kidney) cells, TRPM8 channel is inhibited by the G(i) protein/adenylate cyclase (AC)/cAMP/protein kinase A (PKA) signaling cascade. We further identified the TRPM8 S9 and T17 as two key PKA phosphorylation sites regulating TRPM8 channel activity. the intracellular serine/threonine protein phosphatase 2A (PP2A) dephosphorylates TRPM8 Ser-9 and Thr-17 inhibiting the channel activity. | SIGNOR-273791 |
Q92890 | P01730 | 2 | binding | down-regulates quantity by destabilization | 0.2 | These findings ascribe specific functions to each of the components of the VCP-UFD1L-NPL4 complex in Vpu-mediated CD4 degradation: VCP energizes the process through ATP binding and hydrolysis, UFD1L binds ubiquitinated CD4 through recognition of K48 Ub chains, and NPL4 stabilizes UFD1L. | SIGNOR-252421 |
P41161 | O00712 | 0 | 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-268880 |
Q9HCE7 | P08651 | 1 | ubiquitination | down-regulates quantity | 0.329 | In addition, Smurf1 knockdown also blocked the degradation of endogenous NFI-C in response to TGF-beta1 (XREF_FIG).|In particular, Smurf1 and Smurf2 markedly increased the polyubiquitination of NFI-C in the presence of TGF-beta1 (XREF_FIG and XREF_SUPPLEMENTARY). | SIGNOR-278753 |
Q99594 | Q9GZV5 | 2 | binding | up-regulates | 0.699 | When dephosphorylated, yap/taz enter nuclei and induce gene transcription by interacting with transcription factors tead14. | SIGNOR-201415 |
Q14790 | P53350 | 0 | phosphorylation | down-regulates quantity by destabilization | 0.371 | By phosphorylating S387 in procaspase-8 Cdk1/cyclin B1 generates a phospho-epitope for the binding of the PBD of Plk1. Subsequently, S305 in procaspase-8 is phosphorylated by Plk1 during mitosis. Using an RNAi-based strategy we could demonstrate that the extrinsic cell death is increased upon Fas-stimulation when endogenous caspase-8 is replaced by a mutant (S305A) mimicking the non-phosphorylated form. Together, our data show that sequential phosphorylation by Cdk1/cyclin B1 and Plk1 decreases the sensitivity of cells toward stimuli of the extrinsic pathway during mitosis. | SIGNOR-272989 |
Q53H47 | O14757 | 0 | phosphorylation | down-regulates activity | 0.49 | We previously found that Chk1 phosphorylation of Metnase on S495 enhanced its DNA DSB repair activity but decreased its ability to re-start stalled replication forks. Here we show that phosphorylated Metnase feeds back to increase the half-life of Chk1. Chk1 half-life is regulated by DDB1 targeting it to Cul4A for ubiquitination and destruction. Metnase decreases Chk1 interaction with DDB1, and decreases Chk1 ubiquitination. | SIGNOR-273610 |
P06493 | Q9BTA9 | 1 | phosphorylation | up-regulates activity | 0.2 | Cyclin-dependent kinase 1 (Cdk1) phosphorylates WAC, priming its direct interaction with the polo-box domain of Plk1. Knockdown of WAC compromises Plk1 activity and delays mitotic entry. | SIGNOR-265035 |
P53350 | Q2NKX8 | 1 | relocalization | up-regulates | 0.88 | Human pich was identified as an interaction partner and substrate of plk1. Our data indicate that plk1 prevents the association of pich with chromosome arms and restricts its localization to the kt/centromere region | SIGNOR-152136 |
Q9UK17 | P06241 | 0 | phosphorylation | up-regulates activity | 0.2 | These results indicate that Y108 (for Src-family kinases) and Y136 (for EGFR kinase) are involved in the tyrosine phosphorylation of hKv4.3 channels. | SIGNOR-276396 |
O43150 | P62330 | 1 | gtpase-activating protein | up-regulates activity | 0.668 | Pap is a multidomain protein composed of an N-terminal alpha-helical region with a coiled-coil motif, followed by a pleckstrin homology domain, an Arf-GAP domain, an ankyrin homology region, a proline-rich region, and a C-terminal SH3 domain. In addition, in vitro recombinant Pap exhibits strong GTPase-activating protein (GAP) activity towards the small GTPases Arf1 and Arf5 and weak activity towards Arf6. Pap protein exhibits Arf GAP activity in vitro. | SIGNOR-269706 |
P54756 | Q04760 | 1 | phosphorylation | up-regulates activity | 0.2 | We show that Glo1 activity is promoted by phosphorylation on Tyrosine 136 via multiple kinases. Glo1 Y136 is phosphorylated by multiple different kinases including all members of the Src family. Depletion of multiple different kinases led to a partial reduction in Glo1(Y136) phosphorylation. These included members of the Src family (Src, Yes1, FGR, and the related Abl1), and of the FAK, EPHA, FGFR, and VEGFR families (Figure 2B), suggesting phosphorylation of Glo1 on Y136 by multiple different kinases. In vitro kinase assays revealed that all the members of the Src family, as well as Epha5 and VEGFR3, can efficiently phosphorylate recombinant Glo1 on Y136 (Figure 2C–D). | SIGNOR-276183 |
Q9UKE5 | Q15797 | 1 | phosphorylation | down-regulates activity | 0.2 | Msn kinases directly phosphorylate α-helix 1 of Smad. we have identified Misshapen (Msn) and the mammalian orthologs TNIK, MINK1, and MAP4K4 as the kinases responsible for α-helix 1 phosphorylation. | SIGNOR-276334 |
P01215 | P16473 | 2 | binding | up-regulates | 0.434 | Human thyrotropin (tsh), follitropin (fsh), lutropin (lh), and chorionic gonadotropin (cg) are members of the glycoprotein hormone family derived from heterodimerization of a common ? Subunit with hormone-specific ? Subunits. These hormones were originally purified from the anterior pituitary (tsh, lh, and fsh) and placenta (human cg) and shown to activate specific g protein_coupled receptors in the thyroid (tsh receptor) and gonads (lh and fsh receptors), respectively | SIGNOR-88519 |
P06493 | P30307 | 2 | phosphorylation | up-regulates | 0.858 | Phosphorylation at thr-48, thr-67, ser-122, thr-130, ser-168 and ser-214 occurs at g2 and g2-m transition and is catalyzed by cdk1. Ser-168 phosphorylation levels are lower than those at the other 5 cdk1 sites. Phosphorylation by cdk1 leads to increased activity. | SIGNOR-64960 |
P45983 | O15350 | 1 | phosphorylation | up-regulates activity | 0.42 | Therefore, it is likely that p73 recruitment to the \u0394Np73 promoter is mediated by its JNK-1-dependent phosphorylation. | SIGNOR-279219 |
P35499 | Q92914 | 2 | binding | down-regulates activity | 0.2 | Sodium channel fast inactivation is modulated by alpha subunit interaction with a family of cytoplasmic proteins termed fibroblast growth factor homologous factors (FHFs). In this paper, we report that all A-type FHFs exert rapid onset long-term inactivation on Nav1.6 and other sodium channels. | SIGNOR-253434 |
O75154 | P06493 | 0 | phosphorylation | up-regulates quantity | 0.2 | FIP3 is phosphorylated on S102 in a cell cycle-dependent manner. We identify four sites of phosphorylation of FIP3 in vivo, S-102, S-280, S-347 and S-450 and identify S-102 as a target for Cdk1-cyclin B in vitro. Of these, we show that S-102 is phosphorylated in metaphase and is dephosphorylated as cells enter telophase. | SIGNOR-273588 |
P63096 | Q9NQS5 | 2 | binding | up-regulates activity | 0.284 | 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-256704 |
P30291 | P49841 | 0 | phosphorylation | down-regulates quantity by destabilization | 0.329 | Serine 211 phosphorylation occurred under control conditions in the absence of CK1δ and in the presence of GSK3-β (Fig. 5, D and E). | SIGNOR-276632 |
P25116 | P50148 | 2 | binding | up-regulates activity | 0.582 | 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-257219 |
P11309 | Q92934 | 1 | phosphorylation | down-regulates activity | 0.371 | Pim kinases phosphorylate multiple sites on Bad and promote 14-3-3 binding and dissociation from Bcl-XL. pim kinases are constitutively active when expressed in HEK-293 cells and are able to phosphorylate the Bcl-2 family member Bad on three residues, Ser112, Ser136 and Ser155 in vitro and in cells. | SIGNOR-250390 |
Q16539 | Q9NQU5 | 1 | phosphorylation | up-regulates | 0.2 | The activation of pak6 by both p38 map kinase and mkk6 suggests that pak6 plays a role in the cellular response to stress-related signals. | SIGNOR-130979 |
P28222 | P08754 | 2 | binding | up-regulates activity | 0.437 | 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-256863 |
Q16584 | Q16539 | 0 | phosphorylation | down-regulates | 0.304 | Jnk and p38 mapk activation have antagonistic effects in many cases. From a mechanicistic point of view, the p38 mapk pathway can negatively regulate jnk activity at the level of map3ks, either by phosphorylating mlk3 or the tak1 regulatory subunit tab2 | SIGNOR-166605 |
O00141 | Q96PU5 | 1 | phosphorylation | down-regulates activity | 0.787 | Site‐directed mutagenesis of the SGK1 phosphorylation sites in the Nedd4‐2 protein (S382A,S468ANedd4‐2) and in the EAAT1 protein (T482AEAAT1, T482DEAAT1) significantly blunts the effect of S422DSGK1. Introduction of a negative charge at the SGK phosphorylation site in the EAAT1 protein leads to a strong stimulation of the carrier, whereas replacement with alanine markedly decreases the EAAT1‐mediated current. These observations suggest that SGK1 exerts its effect not only by phosphorylation of Nedd4‐2 but also by phosphorylation of EAAT1. | SIGNOR-263076 |
P43146 | Q01668 | 1 | null | up-regulates activity | 0.297 | DCC activation by a netrin-1 gradient creates a high-level [Ca2+]i gradient by triggering LCC activity and by stimulating the cAMP–PKA pathway, which further activates LCC in the plasma membrane (PM) and Ca2+ channels in the ER. | SIGNOR-268292 |
P37231 | P17676 | 0 | transcriptional regulation | up-regulates quantity | 0.729 | Induction of C/EBP beta DNA-binding activity in NIH-3T3 beta 2 cells exposed to dexamethasone in the presence of insulin and fetal bovine serum activates the expression of an adipocyte-specific nuclear hormone receptor, PPAR gamma, that stimulates the conversion of these fibroblasts into committed preadipocytes | SIGNOR-255730 |
P05556 | Q9GZZ0 | 0 | transcriptional regulation | up-regulates quantity by expression | 0.2 | Consistently, ITGB1 promoter activity was decreased by HOXD1 knockdown in ECs. Furthermore, we identified the putative HOXD1-binding sites in the promoter region of ITGB1. Together, these findings suggest that HOXD1 plays a significant role in EC functions by regulating the expression of ITGB1. | SIGNOR-261648 |
Q13627 | Q8IXJ6 | 1 | phosphorylation | up-regulates activity | 0.293 | This Minibrain/Dyrk1a kinase phosphorylates and activates the Silent information regulator 2/Sirtuin1 deacetylase, which in turn deacetylates and activates the FOXO transcription factor. | SIGNOR-279990 |
Q9UD71 | P17612 | 0 | phosphorylation | up-regulates activity | 0.504 | DARPP-32 (dopamine and cyclic AMP-regulated phospho-protein, relative molecular mass 32,000) is converted into an inhibitor of protein phosphatase 1 when it is phosphorylated by protein kinase A (PKA) at threonine 34.‚ | SIGNOR-250031 |
P27037 | P18075 | 2 | binding | up-regulates | 0.764 | We show that bmp7 and activin bind to the same type ii receptors, actrii and iib, but recruit distinct type i receptors into heteromeric receptor complexes | SIGNOR-60237 |
P61764 | P05771 | 0 | phosphorylation | down-regulates activity | 0.398 | Munc18a is essential for neurotransmitter release by exocytosis and can be phosphorylated by PKC in vitro on Ser-306 and Ser-313. We demonstrate that it is phosphorylated on Ser-313 in response to phorbol ester treatment in adrenal chromaffin cells. Mutation of both phosphorylation sites to glutamate reduces its affinity for syntaxin and so acts as a phosphomimetic mutation. | SIGNOR-249186 |
P15056 | Q05639 | 1 | phosphorylation | down-regulates quantity by destabilization | 0.326 | Mass spectrometry identified in vitro S21 and T88 as phosphorylation sites mediated by B-Raf but not C-Raf on eEF1A1 whereas S21 was phosphorylated on eEF1A2 by both B- and C-Raf. | SIGNOR-276406 |
P78352 | Q9ULH4 | 2 | binding | up-regulates activity | 0.749 | SALMs 1-3 contain a C-terminal PDZ-binding motif, which interacts with PSD-95, an abundant postsynaptic scaffolding protein, whereas SALM4 and SALM5 lack PDZ binding. Interactions between SALMs 1–3 and PSD-95 family proteinscould serve a number of functions. SALM1 and SALM2, which lack the ability to interact with a presynaptic ligand and thus cannot be directly targeted to sites of early synaptic adhesion, may require PSD-95 binding for their localization to early synapses. | SIGNOR-264094 |
P25440 | Q12888 | 1 | relocalization | up-regulates activity | 0.269 | BRD2 is required to recruit 53BP1 to DSBs.|When BRD2 recruitment was blocked with shRNA or JQ1 (Fig. 3a and Supplementary Figure 3c) or a panel of BRD2 siRNAs (Supplementary Figure 3a), the recruitment of 53BP1 to DSBs was significantly delayed. | SIGNOR-262035 |
Q13304 | P08754 | 2 | binding | up-regulates activity | 0.386 | 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-256835 |
O00329 | P16144 | 2 | binding | up-regulates | 0.2 | Stable expression of alpha6beta4 increased carcinoma invasion in a pi3k-dependent manner, and transient expression of a constitutively active pi3k increased invasion in the absence of alpha6beta4. Ligation of alpha6beta4 stimulated significantly more pi3k activity than ligation of beta1 integrins, establishing specificity among integrins for pi3k activation. | SIGNOR-54700 |
P12931 | Q13480 | 1 | phosphorylation | up-regulates | 0.704 | Using both mutagenesis and mass spectrometry approaches, y242, y259, y317, y373 and y627 of gab1 were identified to be phosphorylated by c-src a gab1 mutant with substitutions of the src phosphorylation sites failed to promote hgf-induced dna synthesis | SIGNOR-236314 |
P00533 | Q9ULU4 | 0 | transcriptional regulation | down-regulates quantity by repression | 0.2 | Our quantitative ChIP experiments confirmed that ZMYND8 and JARID1D were co-localized at Slug, CD44, VEGFA, and EGFR genes (Figures 4F–4I). Our ChIP results also showed that ZMYND8 repressed and occupied other JARID1D target genes, such as the matrix metalloproteinase 1 (MMP1) and MMP3, that we previously reported | SIGNOR-262040 |
P31152 | P31749 | 1 | phosphorylation | up-regulates activity | 0.271 | Mechanistically, MAPK4 directly bound and activated AKT by phosphorylation of the activation loop at threonine 308. | SIGNOR-275450 |
P78352 | Q96PV0 | 2 | binding | up-regulates activity | 0.596 | The reversible removal of AIDA-1 from the PSD core under excitatory conditions is similar to the redistribution of another abundant PSD protein, SynGAP. Both SynGAP-alpha1 and AIDA-1 are known to bind PSD-95. | SIGNOR-264229 |
P68431 | Q9H3R0 | 0 | demethylation | down-regulates activity | 0.2 | As one member of the Jumonji-C histone demethylase family, JMJD2C has the ability to demethylate tri- or di-methylated histone 3 and 2 in either K9 (lysine residue 9) or K36 (lysine residue 36) sites by an oxidative reaction, thereby affecting heterochromatin formation, genomic imprinting, X-chromosome inactivation, and transcriptional regulation of genes.JMJD2C has been proved to be a demethylase for H3K9 methylation, in the manner of catalyzing the demethylation of H3K9me3/me2 (the known repressive markers of gene regulation), a histone mark found in heterochromatin associated with euchromatic transcriptional silencing and heterochromatin formation | SIGNOR-263864 |
P07711 | P0DTC2 | 1 | cleavage | up-regulates activity | 0.2 | SARS-2-S can use both CatB/L as well as TMPRSS2 for priming in these cell lines. | SIGNOR-260737 |
O14733 | P53779 | 1 | phosphorylation | up-regulates | 0.582 | Two mapkks, sek1 and mkk7, synergistically activate jnk. Sek1 prefers the tyr-185 residue, and mkk7 prefers the thr-183 residue (17, 19). | SIGNOR-137609 |
O00358 | P07202 | 1 | transcriptional regulation | up-regulates quantity by expression | 0.382 | TSH regulates TPO expression through the cAMP pathway and acts with thyroid-specific transcription factors such as TTF-1, TTF-2 and Pax-8 | SIGNOR-267279 |
Q9Y5H0 | Q9Y5I2 | 2 | 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-265699 |
P46937 | Q6ZWJ1 | 2 | binding | down-regulates activity | 0.2 | WW domain‐containing protein STXBP4 inhibits YAP activity via LATS1‐mediated phosphorylation. | SIGNOR-260013 |
P17096 | Q05655 | 0 | phosphorylation | down-regulates | 0.263 | In this study, we showed that the pkc-mediated phosphorylation of hmg-i exerted a very potent inhibition on the binding of this protein to the at-rich promoter regions of both pkc g and ng genes. The purified hmg-i can be phosphorylated by pkc a,b, g, and d but is poorly phosphorylated by pkc e and z. We have mapped two major sites of phosphorylation by pkc at ser44 and ser64 | SIGNOR-73610 |
O14929 | P62805 | 1 | acetylation | down-regulates activity | 0.2 | Histone acetyltransferase 1 is the founding member of the histone acetyltransferase superfamily and catalyzes lysine acetylation of newly synthesized histone H4|Lys12 for direct attack of the acetyl group of the cofactor.| It is postulated that histone acetylation, through charge neutralization of the cationic histone tails, weakens nucleosomal electrostatic interactions with anionic DNA, thus destabilizing internucleosomal contacts and nucleosomal structure and facilitating access to the promoter region for RNA polymerase and transcription factors. | SIGNOR-264790 |
P43405 | Q92918 | 1 | phosphorylation | up-regulates activity | 0.348 | BCR ligation induced rapid tyrosine-phosphorylation of HPK1 mainly by Syk and Lyn, resulting in its association with BASH and catalytic activation. BCR-mediated activation of HPK1 was impaired in Syk- or BASH-deficient B cells. The functional SH2 domain of BASH and Tyr-379 within HPK1 which we identified as a Syk-phosphorylation site were both necessary for interaction of both proteins and efficient HPK1 activation after BCR stimulation. | SIGNOR-246567 |
Q8IW41 | P05412 | 1 | phosphorylation | up-regulates activity | 0.383 | Consequently, our study clearly determined that p38 MAP kinase-activated MK5 could trigger the activity of c-Jun through phosphorylation of c-Jun, which then bound to the SNAI1 promoter to promote SNAI1-mediated EMT.It has been reported that altering extracellular responses and intracellular signal transduction, such as enhancing the activity of p38MAPK [48], JNK [49] and eIF4 [39] signaling pathways, leads to carcinogenesis and aggravates metastasis.|Western blot analysis showed that MK5 could promote the phosphorylation of c-Jun S63 site and the expression of SNAI1 (Fig.\u00a05a). | SIGNOR-279422 |
Q16695 | Q7LBC6 | 0 | demethylation | down-regulates activity | 0.2 | We have purified a JmjC domain-containing protein, JHDM2A, which specifically demethylates mono- and dimethyl-H3K9. JHDM2A exhibits hormone-dependent recruitment to androgen-receptor target genes, resulting in H3K9 demethylation and transcriptional activation. Thus, our work identifies a histone demethylase and links its function to hormone-dependent transcriptional activation. | SIGNOR-266635 |
Q13627 | P04637 | 1 | phosphorylation | up-regulates | 0.417 | Dyrk1a phosphorylates p53 and inhibits proliferation of embryonic neuronal cells. we found that dyrk1a phosphorylates p53 at ser-15 in vitro and in immortalized rat embryonic hippocampal progenitor h19-7 cells. In addition, dyrk1a-induced p53 phosphorylation at ser-15 led to a robust induction of p53 target genes | SIGNOR-167407 |
Q92600 | O75420 | 2 | binding | up-regulates activity | 0.2 | Through interaction analysis of RQCD1 with full-length or partial proteins of GIGYF1 and GIGYF2, segments corresponding to 620-665th and 667-712th amino acids were identified as potential interacting regions on GIGYF1 and GIGYF2, respectively, with RQCD1. we found that RQCD1 was required for enhancement of the interaction of Grb10 with GIGYF1 and GIGYF2 | SIGNOR-260059 |
P19022 | Q9UQB3 | 2 | binding | up-regulates quantity by stabilization | 0.464 | To clarify the role of p120 in mammalian cells, we have knocked down p120 with siRNA in cells expressing epithelial (E-), placental (P-), neuronal (N-), and vascular endothelial (VE-) cadherins. We report that each of these cadherins, as well as α- and β-catenins, were rapidly degraded in the absence of p120, resulting in loss of cell–cell adhesion. The effect was clearly dose dependent, indicating that p120 expression levels may directly determine cadherin levels. Degradation of p120-uncoupled cadherin occurred after its arrival at the surface, indicating that p120 regulates cadherin turnover at the level of internalization or recycling. p120 homologues ARVCF and δ-catenin could substitute for p120, so at least one family member is likely required to maintain adhesion. Thus, cadherin complexes are rapidly turned over and degraded in mammalian cells in the absence of direct interaction with p120 or a p120 family member. | SIGNOR-252131 |
P63000 | Q9NYF5 | 0 | gtpase-activating protein | down-regulates activity | 0.435 | 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-260503 |
P09086 | P26583 | 2 | binding | up-regulates activity | 0.32 | HMG2 and Oct2 interact via their HMG domains and POU homeodomains, respectively. This interaction is not restricted to Oct2, as other members of the octamer transcription factor family like Oct1 and Oct6 also interact with HMG2. The interaction with HMG2 results in a marked increase in the sequence-specific DNA binding activity of the Oct proteins | SIGNOR-240108 |
Q14790 | Q13158 | 2 | binding | up-regulates activity | 0.931 | Fadd recruits caspase-8 through homotypic interactions of death-effector domains (deds), leading to caspase-8 activation and apoptosis. In turn, fadd recruits the zymogen form of the apoptosis-initiating protease caspase-8, through homophilic interaction of death effector domains. | SIGNOR-112061 |
P17612 | Q93045 | 1 | phosphorylation | down-regulates activity | 0.309 | Using in vitro phosphorylated recombinant protein, four phosphorylation sites were identified in the SCG10 sequence. Ser-50 and Ser-97 were the target sites for protein kinase A. phosphorylation negatively regulates the microtubule-depolymerizing activity of SCG10 and that all four sites participate in this regulation | SIGNOR-250056 |
Q9H2X6 | P46527 | 1 | phosphorylation | up-regulates | 0.254 | Homeodomain-interacting protein kinase-2 stabilizes p27(kip1) by its phosphorylation at serine 10 and contributes to cell motility | SIGNOR-174617 |
P09619 | P24666 | 0 | dephosphorylation | down-regulates activity | 0.308 | Insight into the role of low molecular weight phosphotyrosine phosphatase (LMW-PTP) on platelet-derived growth factor receptor (PDGF-r) signaling. LMW-PTP controls PDGF-r kinase activity through TYR-857 dephosphorylation|On the basis of these results, we propose a key role for LMW-PTP in PDGF-r down-regulation through the dephosphorylation of the activation loop Tyr-857, thus determining a general negative regulation of all downstream signals, with the exception of those elicited by internalized receptors. | SIGNOR-248452 |
Q15768 | P54753 | 2 | binding | up-regulates | 0.821 | Ephrin-b3, a ligand for the receptor ephb3, expressed at the midline of the developing neural tube. | SIGNOR-54711 |
P53004 | P31749 | 0 | phosphorylation | up-regulates activity | 0.296 | Site-directed mutagenesis, mass spectrometry, and kinetic analyses identified S(230) in hBVR (225)RNRYLSF sequence as the Akt1 target. | SIGNOR-275517 |
P50613 | P49736 | 1 | phosphorylation | up-regulates activity | 0.299 | Taken together, these results indicate that Cdc7/Dbf4 phosphorylation of MCM2 is essential for the initiation of DNA replication in mammalian cells. | Because MCM2 was phosphorylated in vivo at Ser27, Ser41, and Ser139, which were phosphorylated by Cdc7/Dbf4 in vitro, the results suggested that Ser27, Ser41, and Ser139 are in vivo Cdc7/Dbf4 phosphorylation sites in MCM2. | SIGNOR-259849 |
P98155 | P10646 | 2 | binding | up-regulates | 0.257 | Binding studies revealed that full-length tfpi, but not the truncated tfpi molecule, is recognized by the very low density lipoprotein receptor (vldl receptor) indicating that this receptor is a novel high affinity endothelial cell receptor for tfpi | SIGNOR-106353 |
P56181 | P06493 | 0 | phosphorylation | up-regulates activity | 0.2 | Here, we show that a fraction of cyclin B1/Cdk1 proteins localizes to the matrix of mitochondria and phosphorylates a cluster of mitochondrial proteins, including the complex I (CI) subunits in the respiratory chain. Cyclin B1/Cdk1-mediated CI phosphorylation enhances CI activity, whereas deficiency of such phosphorylation in each of the relevant CI subunits results in impairment of CI function.|These results were confirmed by generating phosphorylation defective forms of the five CI subunits through substitutions of S/T residues with Alanine (A) on either Cdk1 optimal or minimal consensus motifs (T383 on NDUFV1, S105 on NDUFV3, S364 on NDUFS2, S55/S29/T5 on NDUFB6, and T142/T120 on NDUFA12). The mutation of Cdk1 consensus motifs severely diminished their phosphorylation | SIGNOR-275593 |
P45983 | P42224 | 1 | phosphorylation | up-regulates activity | 0.445 | SP600125 prevented phosphorylation of STAT1 at Tyr701 site [..] Western blot analysis confirmed that blocking p-JNK using SP600125 markedly reduced STAT3 localization in the nucleus and STAT1 phosphorylation | SIGNOR-251101 |
Q8NFU7 | P51608 | 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 |
P18509 | P32241 | 2 | binding | up-regulates | 0.813 | Pacap binds to a pacap-specific receptor (pac1) and to vpac receptors (vpac1 and vpac2), which share high affinity for vasoactive intestinal polypeptide (vip). | SIGNOR-116066 |
Q9NY61 | Q9H2X6 | 0 | phosphorylation | down-regulates quantity | 0.346 | HIPK2 phosphorylates Che-1.|Here we demonstrate that HIPK2, a proapoptotic kinase, is involved in Che-1 degradation. | SIGNOR-278942 |
Q16236 | P06241 | 0 | phosphorylation | down-regulates quantity | 0.4 | Fyn phosphorylates Nrf2 Y568, resulting in nuclear export and degradation of Nrf2.|Fyn phosphorylates Nrf2Y568 resulting in nuclear export and degradation of Nrf2. | SIGNOR-278358 |
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