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 |
|---|---|---|---|---|---|---|---|
Q8TEM1 | P06493 | 0 | phosphorylation | up-regulates activity | 0.549 | In vitro phosphorylation of GST fusion protein containing the carboxyl-terminal domain of gp210 by cyclin B-p34cdc2 protein kinase generates a phosphopeptide that comigrates with a mitosis-specific phosphopeptide. Ser1880 Is the Mitotic Phosphorylation Site of Gp210. | SIGNOR-262699 |
Q96A00 | Q13418 | 0 | phosphorylation | up-regulates activity | 0.549 | Phosphopeptide mapping, phospho amino acid analysis and immunoblotting using phospho-specific antibodies indicated that ilk predominantly phosphorylated the site critical for potent inhibition, i.e. Thr(38) of cpi-17 | SIGNOR-90828 |
O15554 | Q9NRX4 | 0 | dephosphorylation | down-regulates activity | 0.549 | We now show that the mammalian protein histidine phosphatase (PHPT-1) directly binds and inhibits KCa3.1 by dephosphorylating histidine 358 on KCa3.1.|Overexpression of wild-type, but not a phosphatase dead, PHPT-1 inhibited KCa3.1 channel activity. | SIGNOR-277071 |
Q92529 | P04626 | 0 | relocalization | up-regulates | 0.549 | Erbb3 is characterized by a large number of binding sites for phosphatidylinositol-3-kinase (pi3k), while erbb2 has only few interaction partners with shc as the most frequent one. | SIGNOR-146855 |
Q9NS23 | Q13315 | 0 | phosphorylation | up-regulates | 0.549 | We show that, upon dna damage, rassf1a is phosphorylated by atm on ser131 and is involved in the activation of both mst2 and lats1, leading to the stabilization of p73. | SIGNOR-161934 |
P04637 | O14980 | 0 | relocalization | down-regulates activity | 0.549 | We identify the major poly(ADP-ribosyl)ated sites of p53 by PARP-1 and find that PARP-1-mediated poly(ADP-ribosyl)ation blocks the interaction between p53 and the nuclear export receptor Crm1, resulting in nuclear accumulation of p53. These findings molecularly link PARP-1 and p53 in the DNA-damage response, providing the mechanism for how p53 accumulates in the nucleus in response to DNA damage.|PARP-1 is super-activated by binding to damaged DNA, and poly(ADP-ribosyl)ates p53. Poly(ADP-ribosyl)ation probably induces a structural change that mask the NES, and thus Crm1 can no longer target p53 to the nuclear export machinery, resulting in accumulation of p53 in the nucleus. | SIGNOR-260067 |
Q8N157 | P54257 | 0 | binding | up-regulates activity | 0.549 | Huntingtin-associated protein-1 (Hap1) is a regulatory protein that binds Ahi1, and Hap1 knock-out mice have been reported to have JBTS-like phenotypes, suggesting a role for Hap1 in ciliogenesis. | SIGNOR-269081 |
O60296 | O60282 | 0 | binding | up-regulates activity | 0.549 | Trafficking kinesin proteins (TRAKs) are kinesin adaptors. They bind the cargo binding domain of kinesin-1 motor proteins forming a link between the motor and their cargoes. This supports the idea that the KIF5A–TRAK2 interaction is multivalent and could act to ensure stable motor-cargo interaction during intracellular trafficking; dimerization of both motor and adaptor molecules further enhances this stability (Fig. 6). A similar multivalent profile was found for the TRAK2 binding site within the kinesin-1 isoform, KIF5C. | SIGNOR-264064 |
P05112 | O95644 | 0 | transcriptional regulation | up-regulates quantity by expression | 0.549 | Recombinant NFAT1 can mediate transcription of the interleukin-2, interleukin-4, tumor necrosis factor alpha, and granulocyte-macrophage colony-stimulating factor promoters in T cells, suggesting that NFAT1 contributes to the CsA-sensitive transcription of these genes during the immune response. | SIGNOR-254498 |
Q68CJ9 | P49841 | 0 | phosphorylation | down-regulates activity | 0.549 | It is possible that phosphorylation of CREBH by GSK3beta leads to altered CREBH conformation with a resulting decreased affinity toward the COPII coated transport complex.|Similarly, expression of dominant negative GSK3beta can rescue the decreased CREBH cleavage activity in the Bmal1 knockdown hepatocytes under the circadian clock (XREF_FIG), thus confirming that BMAL1 controls circadian regulated CREBH cleavage and activation through AKT and GSK3beta signaling in hepatocytes. | SIGNOR-279785 |
P19793 | P10589 | 0 | binding | up-regulates | 0.549 | Arp-1/rxr, coup-tfi/rxr, and arp-1/coup-tfi heterodimers bound the fp330-3' site | SIGNOR-79440 |
Q9UKC9 | Q9UK99 | 0 | binding | down-regulates quantity by destabilization | 0.549 | F-box protein Fbxo3 targets Smurf1 ubiquitin ligase for ubiquitination and degradation. Here we show that another F-box protein Fbxo3, belonging to the FBXO type protein family, also interacts with and targets Smurf1 for poly-ubiquitination and proteasomal degradation. The SCF complex is composed of F-box protein, Skp1, Cullin1 (Cul1) and ROC1. Fbxo3, whose substrates are few, forms SCF Fbxo3 ubiquitin ligase and regulates the degradations of Fbxl2, p62, HIPK2 and p300 through the ubiquitin-proteasome pathway. | SIGNOR-272445 |
P54274 | Q9H2K2 | 0 | ADP-ribosylation | down-regulates activity | 0.549 | Tankyrase 2 poly(ADP-ribosyl)ated itself and TRF1. Overexpression of tankyrase 2 in the nucleus released endogenous TRF1 from telomeres. | SIGNOR-263376 |
P61586 | Q6P4F7 | 0 | gtpase-activating protein | down-regulates activity | 0.549 | 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-260466 |
O75385 | Q9Y4K3 | 0 | ubiquitination | up-regulates quantity by stabilization | 0.548 | AMBRA1, interacting with the E3-ligase TRAF6, supports ULK1 ubiquitylation by LYS-63-linked chains, and its subsequent stabilization, self-association and function. | SIGNOR-273000 |
P63096 | P35462 | 0 | binding | up-regulates activity | 0.548 | 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-256702 |
Q9NQC7 | O14920 | 0 | phosphorylation | down-regulates activity | 0.548 | Thus, serine 418 is phosphorylated in vivo.Cyld phosphorylation may serve as a mechanism to inactivate its traf2 deubiquitination activity. | SIGNOR-204716 |
Q92949 | P48380 | 0 | binding | up-regulates activity | 0.548 | RFX3 acts as a transcriptional co-activator to FOXJ1 that enhances the expression of cilia-associated genes. FOXJ1 is an important regulator of cilia gene expression during ciliated cell differentiation, with RFX3 as a transcriptional co-activator to FOXJ1, helping to induce the expression of cilia genes in the process of ciliated cell differentiation of basal/progenitor cells. | SIGNOR-266929 |
P61586 | Q9P227 | 0 | gtpase-activating protein | down-regulates activity | 0.548 | 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-260479 |
P29803 | Q15119 | 0 | phosphorylation | down-regulates | 0.548 | Kinetic and regulatory properties of recombinant human pdh2 and pdh1 were compared in this study. Site-specific phosphorylation/dephosphorylation of the three phosphorylation sites by four pdh kinases (pdk1-4) and two pdh phosphatases (pdp1-2) were investigated by substituting serines with alanine or glutamate in pdhs. | SIGNOR-143970 |
P29353 | P36897 | 0 | phosphorylation | up-regulates | 0.548 | We now report that upon TGF-_ stimulation, T_RI phosphorylates ShcA on serine and, to a lesser degree, on tyrosine to activate Erk MAP kinases. | SIGNOR-227503 |
P50542 | O43933 | 0 | binding | up-regulates activity | 0.548 | Pex1, Pex6, and Pex26 are involved in Pex5 export from peroxisomes., we found that Pex1 and Pex6 bind to Pex5 (Fig. (Fig.6). Therefore, it is conceivable that Pex1 and Pex6 pull out Pex5 from peroxisome membranes in an ATP-dependent manner. | SIGNOR-253618 |
Q13085 | P38398 | 0 | binding | down-regulates activity | 0.548 | ACCA binds BRCA1 when phosphorylated onSer1263, thus supporting a model in which controlof lipid synthesis would be mediated at least in part,viaphosphorylation of the Ser1263. | SIGNOR-267474 |
P12830 | O14672 | 0 | cleavage | up-regulates activity | 0.548 | The ADAM proteases are best known for their role in shedding the extracellular domain of transmembrane proteins. Among the transmembrane proteins shed by ADAM10 are notch, HER2, E-cadherin, CD44, L1 and the EGFR ligands, EGF and betacellulin. | SIGNOR-259846 |
Q9ULB1 | P58417 | 0 | binding | up-regulates | 0.548 | Purification of neurexin ialpha revealed that it is tightly complexed to a secreted glycoprotein called neurexophilin 1 | SIGNOR-62775 |
O60934 | P15927 | 0 | binding | up-regulates | 0.548 | The response to replication stress requires the recruitment of rpa and the mre11-rad50-nbs1 (mrn) complex. We observe a direct interaction between rpa with both nbs1 and mre11. By utilizing rpa bound to ssdna, we demonstrate that substituting rpa with phosphorylated rpa or a phosphomimetic weakens the interaction with the mrn complex. | SIGNOR-186651 |
P58400 | P58417 | 0 | binding | up-regulates | 0.548 | Purification of neurexin ialpha revealed that it is tightly complexed to a secreted glycoprotein called neurexophilin 1 | SIGNOR-62699 |
O75581 | P34947 | 0 | phosphorylation | up-regulates | 0.548 | we found that g protein-coupled receptor kinases 5 and 6 (grk5/6), traditionally known to phosphorylate and desensitize 7tm g protein-coupled receptors, directly phosphorylate the pppsp motifs on single transmembrane lrp6 and regulate wnt/lrp6 signaling | SIGNOR-23330 |
P32243 | Q9Y261 | 0 | binding | down-regulates activity | 0.548 | Here we show that OTX2 directly associates with LIM1 and HNF-3beta. The luciferase assay with the P3C sequence, a specific DNA binding sequence for paired-class homeobox genes, has demonstrated that LIM1 enhances, but HNF-3beta represses, OTX2-directed gene expression. | SIGNOR-221164 |
Q9NZV8 | P42658 | 0 | 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 |
Q9UQD0 | Q92915 | 0 | binding | down-regulates activity | 0.547 | 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-253413 |
Q15910 | P24941 | 0 | phosphorylation | up-regulates activity | 0.547 | Here, we demonstrate that the phosphorylation of EZH2 by cyclin-dependent kinases at Thr416 creates a docking site for the ForkHead-associated domain of NIPP1. | SIGNOR-255656 |
P14316 | P42224 | 0 | binding | up-regulates activity | 0.547 | We show that IRF-2 forms a complex with STAT1 and the cytokine-responsive region of the TAP1 promoter in any TPO or IFN-gamma target cells tested. Interaction of IRF-2 and STAT1 on the promoter depends on the DNA-binding domain of IRF-2. | SIGNOR-254532 |
P29474 | P08238 | 0 | binding | up-regulates activity | 0.547 | Here we show that Hsp90 associates with endothelial nitric oxide synthase (eNOS) and is rapidly recruited to the eNOS complex by agonists that stimulate production of nitric oxide, namely vascular endothelial growth factor, histamine and fluid shear stress. Moreover, the binding of Hsp90 to eNOS enhances the activation of eNOS. | SIGNOR-252214 |
P15172 | Q13547 | 0 | binding | down-regulates | 0.547 | Interaction of myod with hdac1 in undifferentiated myoblasts mediates repression of muscle-specific gene expression. | SIGNOR-111243 |
Q5JWF2 | P41968 | 0 | null | up-regulates activity | 0.547 | We hypothesize that XLαs may be involved in this regulatory loop by coupling to melanocortin receptors 3 and 4 in the hypothalamus. | SIGNOR-253068 |
P07900 | Q8TF40 | 0 | 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 |
O14492 | P04629 | 0 | phosphorylation | up-regulates | 0.547 | Two substrates of trk kinases, raps and sh2-b. raps and sh2-b mediate trk signaling in developing neurons | SIGNOR-62619 |
Q13224 | P54829 | 0 | dephosphorylation | down-regulates activity | 0.547 | These previous results, together with the present findings, indicate that STEP61 dephosphorylates the NR2B subunit at its regulatory tyr1472 site, and dephosphorylation of this site leads to internalization of the NMDAR complex from neuronal surface membranes. | SIGNOR-265744 |
P84022 | P29590 | 0 | 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 |
Q9UM73 | P21246 | 0 | binding | up-regulates | 0.547 | We conclude from this series of experiments that ptn specifically binds to the alk orphan receptor as a high affinity ligand at least in part via the putative ligand binding domain described above. | SIGNOR-106411 |
P04637 | O60285 | 0 | phosphorylation | up-regulates | 0.547 | Here we showed that in the presence of wild-type lkb1, nuak1 directly interacts with and phosphorylates p53 in vitro and in vivo. | SIGNOR-172008 |
O14920 | Q02156 | 0 | phosphorylation | up-regulates activity | 0.547 | Monoubiquitylated PKC\u03b5 interacts with a ubiquitin-binding domain in NEMO zinc finger and recruits the cytosolic IKK complex to the plasma membrane, where PKC\u03b5 phosphorylates IKK\u03b2 at Ser177 and activates IKK\u03b2.|These results indicate that PKCepsilon phosphorylates IKKbeta at S177 and activates IKKbeta, which in turn induces PKM2 upregulation. | SIGNOR-278323 |
P15311 | P17252 | 0 | phosphorylation | up-regulates | 0.547 | Phosphorylation of ezrin is required for both conformational activation and for signaling to downstream events. The activating c-terminal threonine phosphorylation on t567 was first described to be downstream of the rho pathway (matsui et al., 1998). Additional studies have implicated protein kinase c (pkc) in the phosphorylation of ezrin t567. | SIGNOR-133223 |
P07355 | P12931 | 0 | phosphorylation | up-regulates | 0.547 | Translocation requires the presence of the annexin 2 binding partner p11 (s100a10) and the phosphorylation of annexin 2 at tyr23 through a src-like tyrosine kinase-dependent mechanism both in vitro and in vivo. | SIGNOR-127872 |
P31751 | P56279 | 0 | binding | up-regulates | 0.547 | Full-length tcl1 and its isoforms bind to akt / in in vitro kinase assays using gsk-3_ as a substrate, we found that the presence of any of the tcl1 family proteins (tcl1, mtcp1, or tcl1b) as gst fusion proteins significantly enhanced akt-induced gsk-3_ phosphorylation | SIGNOR-81683 |
P63092 | P41968 | 0 | binding | up-regulates activity | 0.547 | The melanocortin (MC) receptor family consists of five Gs-coupled receptors that control various physiological functions in response to four distinct agonists, adrenocorticotropic hormone (ACTH, also known as corticotrophin) and alpha, beta, and gamma melanocyte-stimulating hormone (MSH), which are derived from the proopiomelanocortin precursor protein, and two inverse agonists, agouti and agouti-related proteins | SIGNOR-268702 |
O14974 | O43293 | 0 | phosphorylation | down-regulates activity | 0.547 | We conclude from our results Par-4 operates through a "padlock" model in which binding of Par-4 to MYPT1 activates MP by blocking access to the inhibitory phosphorylation sites, and inhibitory phosphorylation of MYPT1 by ZIPK requires "unlocking" of Par-4 by phosphorylation and displacement of Par-4 from the MP complex.|We have also demonstrated that Par-4 is required for agonist induced, ZIPK mediated inhibition of MYPT1 and thus is an important amplifier of inputs to MP. | SIGNOR-279030 |
P29803 | Q16654 | 0 | phosphorylation | down-regulates | 0.547 | Pyruvate dehydrogenase (pdh) activity (pdha) controls the entry of carbohydrate into the tricarboxylic cycle and is regulated by pdh kinase (pdk), which phosphorylates and inactivates the enzyme, and pdh phosphatase, which dephosphorylates the enzyme to the active form | SIGNOR-121936 |
P35558 | Q09472 | 0 | acetylation | down-regulates quantity by destabilization | 0.546 | Acetylation Regulates Gluconeogenesis by Promoting PEPCK1 Degradation via Recruiting the UBR5 Ubiquitin Ligase|P300 Acetylates and Destabilizes PEPCK1|Furthermore, coexpression of P300 increased acetylation levels of wild-type PEPCK1, but not PEPCK13K/R, indicating that P300 acts on these lysine residues of PEPCK1 | SIGNOR-267603 |
Q8N122 | Q15418 | 0 | phosphorylation | up-regulates | 0.546 | Ser719, ser721, and ser722 are the predominant rsk-dependent phosphorylation sites in raptor raptor phosphorylation regulates mtorc1 activity | SIGNOR-180466 |
P17661 | Q96GD4 | 0 | phosphorylation | down-regulates | 0.546 | We report here that aurora-b phosphorylates gfap and desmin in vitro, and this phosphorylation leads to a reduction in filament forming ability. In the present study, we found aurora-b phosphorylates desmin at ser-11, thr-16, and ser-59, in vitro. | SIGNOR-100107 |
Q9Y243 | Q05513 | 0 | phosphorylation | up-regulates activity | 0.546 | Full activation of the PKB enzyme requires phosphorylation of a threonine in the activation | SIGNOR-249153 |
P56945 | Q05209 | 0 | dephosphorylation | down-regulates | 0.546 | Ptp-pest is an efficient negative regulator of lymphocyte activation. This function correlated with the ability of ptp-pest to induce dephosphorylation of shc, pyk2, fak and cas, and inactivate the ras pathway. | SIGNOR-109032 |
P09917 | P49137 | 0 | phosphorylation | up-regulates activity | 0.546 | Arachidonic acid promotes phosphorylation of 5-lipoxygenase at Ser-271 by MAPK-activated protein kinase 2 (MK2). when stimulated with only exogenous arachidonic acid, activity for the S271A mutant was significantly lower as compared with wild type 5-LO. | SIGNOR-250143 |
P10276 | P50613 | 0 | phosphorylation | up-regulates | 0.546 | However, only the coexpression of cdk7 stimulated ser-77 phosphorylation in vivo and enhanced transactivation by rar alpha, but not by a s77a rar mutant. | SIGNOR-49693 |
Q8TAE6 | Q13418 | 0 | phosphorylation | up-regulates activity | 0.546 | Pka predominantly phosphorylated a site distinct from the inhibitory t73 in kepi. Integrin-linked kinase phosphorylated KEPI (T73) and this dramatically increased inhibition of PP1c | SIGNOR-101835 |
P16473 | Q96T91 | 0 | binding | up-regulates | 0.546 | Recombinant a2/b5 heterodimeric glycoproteins, purified using cation exchange and size fractionation chromatography, activated human tsh receptors, but not lh and fsh receptors, and showed high affinity to tsh receptors in a radioligand receptor assay | SIGNOR-88614 |
P17844 | O75925 | 0 | sumoylation | up-regulates | 0.546 | We demonstrate that the sumo e3 ligase pias1 interacts with p68 and enhances its sumo modification in vivo / sumo modification enhances p68 transcriptional repression activity and inhibits the ability of p68 to function as a coactivator of p53. | SIGNOR-153719 |
Q9H4A3 | Q9Y3S1 | 0 | phosphorylation | up-regulates activity | 0.546 | WNK1, which is activated in response to osmotic stress by phosphorylation of its T-loop residue (Ser382). | We found that wild-type WNK2 (Figure 8A) or WNK3 (Figure 8B) phosphorylated kinase-inactive WNK1 (1–667, D368A) at Ser382 in vitro. | SIGNOR-260790 |
O00206 | P06702 | 0 | binding | up-regulates activity | 0.546 | RAGE and TLR4 are well-characterized S100A8 and S100A9 receptors and expressed in AML cells. S100A9 binds to TLR4 and induces signaling pathways,promoting leukemic cell differentiation and proliferation arrest. Binding of S100A9 to TLR4 stimulates the phosphorylation of JNK, ERK1/2, and p38 MAPK, which leads to the activation of c-Jun, CREB, and NF-kB. | SIGNOR-261918 |
P03372 | Q96FW1 | 0 | deubiquitination | down-regulates activity | 0.546 | OTU Domain-containing ubiquitin aldehyde-binding protein 1 (OTUB1) deubiquitinates estrogen receptor (ER) alpha and affects ERalpha transcriptional activity.|We show that OTUB1 negatively regulates transcription mediated by ERalpha in transient reporter gene assays and transcription mediated by endogenous ERalpha in Ishikawa endometrial cancer cells. | SIGNOR-276529 |
P63000 | Q8IWW6 | 0 | gtpase-activating protein | down-regulates activity | 0.546 | 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-260469 |
O60285 | Q15831 | 0 | phosphorylation | up-regulates | 0.546 | A total of 12 human kinases (nuak1, nuak2, brsk1, brsk2, qik, qsk, sik, mark1, mark2, mark3, mark4 and melk) are related to ampk. Here we demonstrate that lkb1 can phosphorylate the t-loop of all the members of this subfamily, apart from melk, increasing their activity >50-fold. | SIGNOR-122686 |
P19174 | Q9UM73 | 0 | binding | up-regulates | 0.546 | Proteins that interact with alk tyrosine kinase play important roles in mediating downstream cellular signals. Previously reported proteins in the alk signal pathway were identified including pi3-k, jak2, jak3, stat3, grb2, irs, and plcgamma1. | SIGNOR-122082 |
O75581 | Q9HCP0 | 0 | phosphorylation | up-regulates | 0.545 | Ck1gamma is associated with lrp6, which has multiple, modular ck1 phosphorylation sites. Wnt treatment induces the rapid ck1gamma-mediated phosphorylation of these sites within lrp6 | SIGNOR-143029 |
P43405 | Q06124 | 0 | dephosphorylation | down-regulates activity | 0.545 | Another SHP isoform, SHP-2, has been linked to negative regulation of Syk.|Syk and LAT are differentially dephosphorylated by SHP-2 and SHP-1, respectively. | SIGNOR-277085 |
P30291 | Q9UNH5 | 0 | dephosphorylation | up-regulates quantity by stabilization | 0.545 | In particular, we found that Cdc14A inhibits Wee1 degradation through the dephosphorylation of Ser-123 and Ser-139 residues. | SIGNOR-267470 |
O00459 | P03372 | 0 | binding | up-regulates | 0.545 | Recently, it has been known that er activates phosphatidylinositol-3-oh kinase (pi3k) through binding with the p85 regulatory subunit of pi3k. | SIGNOR-140473 |
P10275 | Q07912 | 0 | phosphorylation | up-regulates activity | 0.545 | Ack1 interacted with and phosphorylated AR protein at Tyr 267 and Ack1 was shown to be required for optimal AR target gene expression and AR recruitment.|Two intracellular tyrosine kinases, Ack1 (activated cdc42 associated kinase) and Src, phosphorylate and enhance AR activity and promote prostate xenograft tumor growth in castrated animals. | SIGNOR-278194 |
Q06187 | P07948 | 0 | phosphorylation | up-regulates | 0.545 | Phosphorylation at y551 requires lyn kinase activity, indicating that y551 is a transphosphorylation site \ this transphosphorylation at y551 is followed by phosphorylation at a second site, which is dependent on btk catalytic activity. | SIGNOR-41607 |
Q6VY07 | P68400 | 0 | phosphorylation | up-regulates activity | 0.545 | Phosphorylation of Ser278 by CK2 or a Ser278-->Asp mutation increased the interaction between PACS-1 and cargo, whereas a Ser278-->Ala substitution decreased this interaction. Moreover, the Ser278-->Ala mutation yields a dominant-negative PACS-1 molecule that selectively blocks retrieval of PACS-1-regulated cargo molecules to the TGN. | SIGNOR-250925 |
Q9NR28 | Q07812 | 0 | relocalization | up-regulates | 0.545 | Bax and/or bak-mediated release of pro-apoptotic mediators including smac/diablo and omi | SIGNOR-87109 |
O43379 | Q96SN8 | 0 | relocalization | up-regulates activity | 0.545 | Primary microcephaly (MCPH) associated proteins CDK5RAP2, CEP152, WDR62 and CEP63 colocalize at the centrosome. We found that they interact to promote centriole duplication and form a hierarchy in which each is required to localize another to the centrosome, with CDK5RAP2 at the apex, and CEP152, WDR62 and CEP63 at sequentially lower positions. MCPH proteins interact with distinct centriolar satellite proteins; CDK5RAP2 interacts with SPAG5 and CEP72, CEP152 with CEP131, WDR62 with MOONRAKER, and CEP63 with CEP90 and CCDC14. These satellite proteins localize their cognate MCPH interactors to centrosomes and also promote centriole duplication. Consistent with a role for satellites in microcephaly, homozygous mutations in one satellite gene, CEP90, may cause MCPH. The satellite proteins, with the exception of CCDC14, and MCPH proteins promote centriole duplication by recruiting CDK2 to the centrosome. | SIGNOR-271723 |
Q99496 | Q6W2J9 | 0 | binding | up-regulates activity | 0.545 | BcoR and Fbxl10/Jhdm1B are among the most abundant Ring1B/Rnf2 interactors identified with the highest confidence, and their association has been validated by coimmunoprecipitation studies; hence we call this the Fbxl10-BcoR complex. In summary, we have widened the set of multiprotein complexes containing the Polycomb group protein Ring1B/Rnf2. The new interactors contain protein motifs whose enzymatic activities and binding properties would expand the regulatory potential and gene target diversity of Ring1B/Rnf2 complexes in terms of recruitment to and modification of chromatin | SIGNOR-252241 |
P41229 | O95628 | 0 | ubiquitination | down-regulates quantity by destabilization | 0.545 | In our study, we show that the protein level of the yeast histone H3 Lys 4 (H3 K4) demethylase Jhd2/Kdm5 is modulated through polyubiquitination by the E3 ubiquitin ligase Not4 and turnover by the proteasome. Finally, we show that human NOT4 can polyubiquitinate human JARID1C/SMCX, a homolog of Jhd2, suggesting that this is likely a conserved mechanism. We propose that Not4 is an E3 ubiquitin ligase that monitors and controls a precise amount of Jhd2 protein so that the proper balance between histone demethylase and histone methyltransferase activities occur in the cell, ensuring appropriate levels of H3 K4 trimethylation and gene expression. | SIGNOR-271468 |
Q9UM73 | P23471 | 0 | dephosphorylation | down-regulates | 0.545 | Rptpbeta/zeta dephosphorylates alk at the site(s) in alk that is undergoing autophosphorylation through autoactivation. | SIGNOR-157227 |
P63000 | Q96N67 | 0 | guanine nucleotide exchange factor | up-regulates activity | 0.545 | As a GEF, Dock7 exchanges GDP for GTP on Cdc42 and Rac1, causing their activation, followed by activation of downstream effectors, including the dephosphorylation (activation) of cofilin, a key regulator of actin turnover. | SIGNOR-261887 |
P05067 | Q9Y5Z0 | 0 | cleavage | up-regulates activity | 0.544 | BACE2, a beta -secretase homolog, cleaves at the beta site and within the amyloid-beta region of the amyloid-beta precursor protein.|Figure 6 Preferred BACE1 and BACE2 cleavage sites. (A) Sequence of APP indicating α- and β-cleavage sites, BACE1- and BACE2-cleavage sites, and the location of mutations analyzed here. APP numbering is that of the 770-aa isoform. | SIGNOR-261773 |
Q9NQC7 | O15111 | 0 | phosphorylation | up-regulates activity | 0.544 | The phosphorylation of cyld was completely abolished by the combined mutations of the entire serine cluster (m4, lane 5). Similar results were obtained with the ikk holoenzyme (fig. 4c, panel 1), recombinant ikk_ (panel 2), and recombinant ikk_cyld phosphorylation may serve as a mechanism to inactivate its traf2 deubiquitination activity. | SIGNOR-204692 |
Q9NZJ0 | Q86XK2 | 0 | binding | down-regulates | 0.544 | We determined that the f-box protein fbxo11 interacts with cdt2,a dcaf protein that controls cell-cycle progression, and recruits cdt2 to the scf(fbxo11)complex to promote its proteasomal degradation. | SIGNOR-192325 |
P46937 | Q9Y297 | 0 | ubiquitination | down-regulates | 0.544 | This cascade of phosphorylation allows the binding of scfbetatrcp that promotes the ubiquitination and degradation of yap. | SIGNOR-201138 |
Q14289 | Q05209 | 0 | dephosphorylation | down-regulates activity | 0.544 | Inhibition of the catalytic activity of cell adhesion kinase beta by protein-tyrosine phosphatase-pest-mediated dephosphorylation. / dephosphorylation of tyr402 and tyr579/580 by ptp-pest | SIGNOR-107502 |
Q53ET0 | Q13131 | 0 | phosphorylation | down-regulates | 0.544 | Collectively, these findings suggest ampk suppresses glucose production through two transcriptional effects:reduced expression of creb targets via crtc inactivation and reduced expression of foxo target genes via class iia hdac inactivation | SIGNOR-176426 |
Q9UM11 | Q9UI95 | 0 | binding | down-regulates activity | 0.544 | The APC is activated in mitosis and G1 by CDC20 and CDH1, and inhibited by the checkpoint protein MAD2, a specific inhibitor of CDC20. We show here that a MAD2 homolog MAD2B also inhibits APC. MAD2B directly inhibits activation of APC by CDC20 and CDH1 | SIGNOR-264902 |
P04083 | Q96QT4 | 0 | phosphorylation | up-regulates | 0.544 | Trpm7 was responsible for phosphorylation of the serine 5 (ser5) residue [29]. In 2009, the study focused on an association between anxa1 and trpm7 confirmed the presence of a trpm7/annexin a1/mg2_+ complex, suggesting a novel pathway in bradykinin signaling, dependent on pkc and c-src [30]. Even though that pathway is not fully characterized, the same team that discovered the ser5 phosphorylation of anxa1 also reported crucial relevance of this modification for anxa1 membrane binding and especially for the interaction between annexin a1 and its known partner, the calcium binding protein s100a11 | SIGNOR-202804 |
P50148 | Q92633 | 0 | binding | up-regulates activity | 0.544 | 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-257091 |
P46934 | P68036 | 0 | ubiquitination | up-regulates activity | 0.544 | 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-272735 |
Q08211 | Q9ULX6 | 0 | binding | up-regulates activity | 0.544 | We report evidence for a novel nuclear export signal in HAP95 and showed that the domains involved in RHA binding and nuclear localization are required for CTE activation. Finally, we showed that HAP95 synergizes significantly with RHA on CTE-mediated reporter gene expression and promotes nuclear export of unspliced mRNA in transfected cells. Taken together, these data support the proposal that HAP95 specifically facilitates CTE-mediated gene expression by directly binding to RHA. | SIGNOR-260950 |
P16157 | Q92823 | 0 | relocalization | up-regulates quantity | 0.544 | Neurofascin, L1, NrCAM, NgCAM, and neuroglian are membrane-spanning cell adhesion molecules with conserved cytoplasmic domains that are believed to play important roles in development of the nervous system. This report presents biochemical evidence that the cytoplasmic domains of these molecules associate directly with ankyrins, a family of spectrin-binding proteins located on the cytoplasmic surface of specialized plasma membrane domains. | SIGNOR-266721 |
Q07666 | P06241 | 0 | phosphorylation | up-regulates activity | 0.544 | The tyrosine kinase Fyn modulates Sam68 mediated alternative splicing of Bcl-x mRNA.|Tyrosine phosphorylation of Sam68 by Fyn inverted this effect and favored the Bcl-x(L) splice site selection. | SIGNOR-279462 |
Q13705 | P18075 | 0 | binding | up-regulates | 0.544 | 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-60240 |
Q8N8S7 | Q70E73 | 0 | binding | up-regulates activity | 0.544 | Here we show that Lpd is a substrate of Abl kinases and binds to the Abl SH2 domain. Phosphorylation of Lpd positively regulates the interaction between Lpd and Ena/VASP proteins. | SIGNOR-268425 |
P02458 | P45452 | 0 | cleavage | down-regulates quantity by destabilization | 0.544 | Although it appears that MMP-1 and MMP-13 both cleave type II collagen initially at the same site, MMP-13 affects a secondary cleavage to produce a 1/4-size collagen fragment with an NH2 terminus three amino acids removed from the primary cleavage site.The present work has demonstrated expression of MMP-13 in human osteoarthritic cartilage and shown that MMP-13 has significant type II collagen degrading activity. | SIGNOR-256340 |
Q9NS23 | Q8WWW0 | 0 | binding | up-regulates activity | 0.543 | NORE1A can heterodimerize with RASSF1A and, thus, mediate K-Ras regulation of RASSF1A | SIGNOR-249587 |
Q14457 | Q9Y371 | 0 | binding | up-regulates | 0.543 | Bif-1 forms a complex with beclin1 through uvrag and promotes the activation of the class iii pi3 kinase, vps34, in mammalian cells. | SIGNOR-171899 |
P60953 | Q7Z5H3 | 0 | gtpase-activating protein | down-regulates activity | 0.543 | 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-260478 |
P46531 | P84022 | 0 | binding | up-regulates | 0.543 | Nicd and smad3 were shown to interact directly, both in vitro and in cells, in a ligand-dependent manner, and smad3 could be recruited to csl-binding sites on dna in the presence of csl and nicd | SIGNOR-119374 |
Q969U6 | O00444 | 0 | phosphorylation | down-regulates activity | 0.543 | The activity of SCF-FBXW5 is in turn negatively regulated by Polo-like kinase 4 (PLK4), which phosphorylates FBXW5 at Ser 151 to suppress its ability to ubiquitylate HsSAS-6. | SIGNOR-275476 |
O15146 | Q9UPQ7 | 0 | ubiquitination | down-regulates quantity | 0.543 | We have identified a PDZ domain containing RING finger 3 (PDZRN3) as a synapse-associated E3 ubiquitin ligase and have demonstrated that it regulates the surface expression of muscle-specific receptor tyrosine kinase (MuSK), the key organizer of postsynaptic development at the mammalian neuromuscular junction. PDZRN3 binds to MuSK and promotes its ubiquitination. Together, these data demonstrate that PDZRN3 is a catalytically active RING-type E3 ubiquitin ligase | SIGNOR-271664 |
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