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 |
|---|---|---|---|---|---|---|---|
O95644 | Q08209 | 0 | dephosphorylation | up-regulates | 0.825 | Calcineurin directly dephosphorylates nfat resulting in the nuclear import of nfat. | SIGNOR-176370 |
Q14164 | Q96AQ6 | 1 | phosphorylation | down-regulates quantity by destabilization | 0.2 | Accordingly, we identified the microtubule-associated HPIP, a positive regulator of oncogenic AKT signaling, as a novel MDM2 substrate. MDM2-dependent HPIP degradation occurs in breast cancer cells on its phosphorylation by the estrogen-activated kinase TBK1. | SIGNOR-276618 |
Q9UKV8 | P00533 | 0 | phosphorylation | up-regulates activity | 0.534 | Furthermore, AGO2 function is directly modulated by EGFR signaling in ERalpha negative breast cancer under states of hypoxic stress.|Here, EGFR can directly bind and phosphorylate residue Y393 of AGO2[ xref ]. | SIGNOR-278931 |
Q96EB6 | P35222 | 1 | deacetylation | up-regulates quantity | 0.505 | SIRT1 deacetylates β-catenin to promote its accumulation in the nucleus and thus induces the transcription of genes that block MSC adipogenesis. | SIGNOR-256208 |
O95257 | Q9UQ88 | 2 | binding | down-regulates activity | 0.2 | Western blot analysis for SPDEF revealed that overexpression of GADD45α, β and γ prevents SPDEF degradation mediated by CDK11p58 |We identified CDK11p58 as an interaction partner of GADD45α by co-immunoprecipitation analysis. We corroborated these data by co-immunoprecipitation in vitro translation assays, showing that all three members of the GADD45 family interact with CDK11p58. | SIGNOR-273025 |
P23771 | P24941 | 0 | phosphorylation | down-regulates quantity by destabilization | 0.362 | Phosphorylation of GATA3 Thr-156 was detected in mouse thymocytes, and cyclin-dependent kinase 2 (CDK2) was identified as a respondent for phosphorylation at Thr-156. | SIGNOR-276634 |
P54646 | Q53ET0 | 1 | phosphorylation | down-regulates | 0.489 | Phosphorylation on the ser171 residue of crtc2 by ampk and ampk-related kinases, including the salt-inducible kinases (siks), is critical for determining the activity, cellular localization, and degradation of crtc2 | SIGNOR-142211 |
O14641 | Q9UP38 | 2 | binding | up-regulates activity | 0.678 | Upon ligand binding, DVL proteins are recruited to Frizzled receptors at the plasma membrane and co-recruit cytoplasmic transducers, such as Axin, CK1 and GSK3 binding protein (GBP), presumably along with their partners, to promote ?-catenin-dependent signalling. | SIGNOR-258952 |
Q9NZL9 | Q9Y2X7 | 2 | binding | up-regulates activity | 0.398 | We found both MAT2B variants interact with GIT1. MAT2B directly promoted binding of GIT1 and ERK2 to MEK1. MAT2B and GIT1 interact and are overexpressed in most human liver and colon cancer specimens. MAT2B and GIT1 require each other to activate MEK1/ERK and increase growth. | SIGNOR-261244 |
P00533 | P29350 | 0 | dephosphorylation | down-regulates | 0.415 | The sh2-domain ptpase shp-1 binds to and dephosphorylates autophosphorylated egfr and may participate in modulation of egfr signaling in epithelial cells. Reduced shp-1 binding to the egfr y1173f mutant resulted in a reduced receptor dephosphorylation by coexpressed shp-1 and less interference with egf-dependent mitogen-activated protein kinase stimulation. | SIGNOR-59965 |
P49841 | Q2M1Z3 | 1 | phosphorylation | up-regulates activity | 0.302 | We show that GSK-3alpha and -beta interact with CdGAP in mammalian cells. We also demonstrate that GSK-3 phosphorylates CdGAP both in vitro and in vivo on Thr-776, which we have previously shown to be an ERK 1/2 phosphorylation site involved in CdGAP regulation. | SIGNOR-262879 |
Q13315 | P48730 | 1 | phosphorylation | up-regulates activity | 0.34 | These results elucidated the specificity of this in vivo degradation assay, and further implicated that CKI\u03b4-dependent phosphorylation events is the major signaling route through which DNA damage-dependent activation of ATM might control timely turnover of Mdm2 during genotoxic stress. (A) ATM-mediated phosphorylation of CK1\u03b4 promotes CK1\u03b4 nuclear localization.|We further demonstrated that DNA damage-induced activation of ATM directly phosphorylated CKI\u03b4 at two well-conserved S/TQ sites, which promotes CKI\u03b4 nuclear localization to increase CKI\u03b4-mediated phosphorylation of Mdm2, thereby facilitating subsequent Mdm2 ubiquitination by SCF\u03b2-TRCP. | SIGNOR-279504 |
P63092 | P41231 | 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 ‚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-256759 |
Q15034 | Q04206 | 1 | ubiquitination | down-regulates quantity by destabilization | 0.325 | Our data so far suggest that HERC3 reduces NF-kappaB transcriptional activity by binding to the proteasome and delivering RelA for degradation.|We show that HERC3 mediates ubiquitination of RelA on two distinct lysine residues, K195 and K315. | SIGNOR-278546 |
P63167 | Q13153 | 0 | phosphorylation | down-regulates | 0.378 | Dlc1 phosphorylation on ser(88) by p21-activated kinase 1 (pak1), a signaling nodule, promotes mammalian cell survival by regulating its interaction with bim and the stability of bim. Here we discovered that phosphorylation of ser(88), which juxtapose each other at the interface of the dlc dimer, disrupts dlc1 dimer formation and consequently impairs its interaction with bim | SIGNOR-159995 |
P78527 | Q13426 | 1 | phosphorylation | up-regulates activity | 0.907 | In response to ionizing radiation, ATM phosphorylates FBXW7 at serine 26 to recruit it to DNA double-strand break (DSB) sites, whereas activated DNA-PKcs phosphorylates XRCC4 at serines 325/326, which promotes binding of XRCC4 to FBXW7. SCF(FBXW7) E3 ligase then promotes polyubiquitylation of XRCC4 at lysine 296 via lysine 63 linkage for enhanced association with the Ku70/80 complex to facilitate NHEJ repair. | SIGNOR-277198 |
P68400 | Q01082 | 1 | phosphorylation | down-regulates | 0.334 | We show here that the short c-terminal splice variant of betaii-spectrin (betaiisigma2) is a substrate for phosphorylation. In vitro, protein kinase ck2 phosphorylates ser-2110 and thr-2159 / phosphorylation of ?II?2 C-terminal fragment inhibits its interaction with ?II N-terminal fragment. | SIGNOR-150471 |
P01116 | P48736 | 2 | binding | up-regulates | 0.778 | Grb2 binds and activates sos, which then activates ras, and this activates p110 independently of p85./it was also described that ras interacts with pi3k in a direct manner. | SIGNOR-59819 |
Q5XUX0 | Q12834 | 2 | binding | down-regulates quantity by destabilization | 0.398 | Here we show that the low levels of FBXO31 are maintained through proteasomal degradation by anaphase-promoting complex/cyclosome (APC/C). We find that the APC/C coactivators CDH1 and CDC20 bind to a destruction-box (D-box) motif present in FBXO31 to promote its polyubiquitination and degradation in a cell-cycle-regulated manner, which requires phosphorylation of FBXO31 on serine-33 by the prosurvival kinase AKT. | SIGNOR-277378 |
Q00535 | Q15303 | 1 | phosphorylation | up-regulates activity | 0.278 | Cdk5 Promotes ErbB4 and PI3-Kinase Activity In Vivo.|Cdk5 phosphorylates ErbB4 at T1152, situated in close proximity to the PI3-kinase-binding site (Y1056), and in turn promotes ErbB4 tyrosine phosphorylation. | SIGNOR-278436 |
P22607 | P09038 | 2 | binding | up-regulates | 0.82 | Fgf-2 and fgf-9 increased expression of other osteogenic factors bmp-2 and tgf-beta1, and endogenous fgf/fgfr signaling is a positive upstream regulator of the bmp-2 gene in calvarial osteoblasts. | SIGNOR-134788 |
Q8TDV5 | P19086 | 2 | binding | up-regulates activity | 0.25 | 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-257308 |
Q13485 | Q92905 | 0 | ubiquitination | down-regulates | 0.433 | We report a novel mechanism of smad4 degradation. Jab1 interacts directly with smad4 and induces its ubiquitylation for degradation | SIGNOR-114697 |
Q15398 | Q9UPX8 | 1 | relocalization | up-regulates activity | 0.452 | SHANK proteins are ‘master’ scaffolding proteins that tether and organize intermediate scaffolding proteins. They are located at excitatory synapses, where they are crucial for proper synaptic development and function. SAPAP proteins subsequently bind to the PDZ domain of members of the SHANK protein family. SHANK proteins then bind to the actin cytoskeleton and to Homer protein, which in turn interacts with mGluRs. Through these extended links, PSD95, SAPAP, SHANK and Homer proteins form a quaternary complex that brings together mGluR and NMDAR complexes in the PSD (FIG. 3). | SIGNOR-264599 |
P27361 | P17542 | 1 | phosphorylation | down-regulates | 0.357 | We report here that the important proangiogenic stimulus hypoxia stimulates phosphorylation, ubiquitination, and proteasomal breakdown of tal1 in endothelial cells. A specific serine in the putative transactivation domain of the protein, ser122, is preferentially phosphorylated by mapk in vitro. | SIGNOR-116153 |
O75460 | Q99683 | 0 | phosphorylation | up-regulates activity | 0.618 | ASK1 may directly phosphorylate IRE1\u03b1 at sites other than the IRE1\u03b1 autophosphorylation site. | SIGNOR-279213 |
Q9UKT8 | Q86Y07 | 0 | phosphorylation | down-regulates activity | 0.296 | Collectively, CK1 and VRK2, but not GRK2 kinase, appears to mediate FBXW2 phosphorylation at the beta-TrCP binding motif.|We followed this lead, and inactivated VRK2 and GRK2 by siRNA silencing, or CK1 and VRK2 by small molecule inhibitor IC-261, and found that GRK2 knockdown had no effect, whereas CK1 and VRK2 inhibition or VRK2 silencing largely blocked the degradation of exogenously expressed FBXW2 (XREF_FIG and XREF_SUPPLEMENTARY). | SIGNOR-280161 |
Q9Y572 | Q9Y572 | 2 | phosphorylation | up-regulates activity | 0.2 | This suggests that Thr182 is a likely auto-phosphorylation target and may be involved in RIP3 activity. | SIGNOR-277396 |
P31749 | P53004 | 1 | 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 |
P54646 | Q13315 | 0 | phosphorylation | up-regulates activity | 0.264 | ATM phosphorylates AMPKalpha2 to induce inhibitory phosphorylation of HIPK2| | SIGNOR-275488 |
P31749 | O14746 | 1 | phosphorylation | up-regulates | 0.732 | Akt kinase enhances human telomerase activity through phosphorylation of htert subunit as one of its substrate proteins. | SIGNOR-67313 |
P61586 | O14640 | 2 | binding | up-regulates activity | 0.624 | Although there are other activators of PCP, Wnt5a can activate the PCP pathway by forming a complex with Fzd and Ror2 receptors, activating DVL, which in turn activates Rho-family small GTPases, including RhoA and Rac, and their downstream effectors, Rho-associated protein kinase (ROCK), the actin-binding protein, Filamin A and c-Jun N-terminal protein kinase (JNK) | SIGNOR-258971 |
Q14344 | Q9H1C0 | 2 | binding | up-regulates activity | 0.35 | 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-257284 |
Q01860 | P31751 | 0 | phosphorylation | up-regulates quantity by stabilization | 0.255 | Here we show that in ECCs, Akt phosphorylated the master pluripotency factor Oct4 at threonine 235, and that the levels of phosphorylated Oct4 in ECCs correlated with resistance to apoptosis and tumorigenic potential. Phosphorylation of Oct4 increased its stability and facilitated its nuclear localization and its interaction with Sox2, which promoted the transcription of the core stemness genes POU5F1 and NANOG. | SIGNOR-242097 |
Q9HCD6 | Q12756 | 2 | binding | up-regulates activity | 0.248 | Kinesin-3 Family Member KIF1A Interacts with Liprin-α and TANC2. TANC2 and Liprin-α Recruit KIF1A-Driven DCVs in Dendritic Spines. Upon Ca2+/CaM binding, KIF1A is activated, allowing for DCV loading and motility. KIF1A-driven DCVs are recruited in dendritic spines by liprin-α and TANC2, which ensure a precise mechanism of synaptic tagging for the vesicles. | SIGNOR-266891 |
Q9HA47 | Q96RU2 | 0 | deubiquitination | up-regulates quantity by stabilization | 0.2 | We demonstrated that the ubiquitin E3 ligase KLHL2 interacted with UCK1 and mediated its polyubiquitination at the K81 residue and degradation. We showed that deubiquitinase USP28 antagonized KLHL2-mediated polyubiquitylation of UCK1. | SIGNOR-275855 |
Q6NUN9 | P00519 | 0 | phosphorylation | up-regulates activity | 0.313 | C-Abl-mediated phosphorylation of PARIS at Y137 (within the Krüppel-associated box domain) drives its association with KAP1 and the repression of genes with diverse functions in pathways such as chromatin remodelling and p53-dependent cell death. | SIGNOR-277626 |
Q8TDC3 | Q15831 | 0 | phosphorylation | up-regulates | 0.485 | Lkb1 is a master kinase that activates 13 kinases of the ampk subfamily, including mark/par-1we recently demonstrated that the lkb1 tumour suppressor kinase, in complex with the pseudokinase strad and the scaffolding protein mo25, phosphorylates and activates amp-activated protein kinase (ampk). 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-122413 |
P16144 | P48736 | 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-54703 |
P08581 | P40818 | 0 | destabilization | down-regulates quantity | 0.456 | Degradation of acutely stimulated receptor tyrosine kinases, epidermal growth factor receptor and Met, is strongly inhibited in UBPY knockdown cells suggesting that UBPY function is essential for growth factor receptor down-regulation. | SIGNOR-266903 |
O95837 | P32238 | 2 | binding | up-regulates activity | 0.459 | 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-257361 |
P46531 | P51608 | 0 | transcriptional regulation | down-regulates quantity by repression | 0.29 | As the first step to reveal how MeCP2 phosphorylation may regulate Notch signaling, we conducted chromatin immunoprecipitation (ChIP) experiment to determine whether the phosphor-mutant MeCP2 protein has altered promoter occupancy at the promoters of Dll1 and Notch1. We found increased binding of the phosphor-mutant protein at the promoters of both Dll1 and Notch1 | SIGNOR-264675 |
P01106 | Q13049 | 0 | ubiquitination | down-regulates quantity by destabilization | 0.456 | TRIM32 ubiquitinates and degrades the transcription factor c-Myc but also binds Argonaute-1 and thereby increases the activity of specific microRNAs. | SIGNOR-278676 |
O75581 | Q9H0K1 | 0 | phosphorylation | up-regulates activity | 0.2 | Mechanistically, SIK2, phosphorylated by CK1α, directly phosphorylated LRP6 in a SIK2 kinase activity-dependent manner, leading to Wnt/β-catenin signaling pathway activation. | SIGNOR-275399 |
Q14980 | P23258 | 2 | binding | up-regulates | 0.618 | Direct binding of numa to tubulin is mediated by a novel sequence motif in the tail domain that bundles and stabilizes microtubules. | SIGNOR-117203 |
P53350 | P52565 | 1 | phosphorylation | up-regulates activity | 0.2 | PLK1 phosphorylates RhoGDI1 at Thr7/91 residue in vitro and in vivo. Collectively, we demonstrate that the phosphorylation of RhoGDI1 by PLK1 promotes cancer cell migration and invasion through RhoA activation. | SIGNOR-277882 |
Q15418 | P29317 | 1 | phosphorylation | up-regulates activity | 0.292 | These comprehensive analyses indicate that high matrix stiffness activates ERK/RSK1-mediated EPHA2 non-canonical signalling to induce LYN activation, TWIST1 nuclear localization, and cell invasion (Fig. 6M).|We next knocked down the most abundant RSK family members and found that loss of RSK1, but not RSK2 or RSK3, drastically inhibited EPHA2 S897 phosphorylation, prevented ECM stiffness-induced LYN activation and recruitment to EPHA2, and inhibited cell EMT and invasion induced by increasing rigidities (Fig. 6F\u2013I and S6H\u2013L). | SIGNOR-280113 |
P14778 | P45984 | 1 | phosphorylation | up-regulates activity | 0.281 | Il-1 binding to its receptor triggers a cascade of signaling events, including activation of the stress-activated mitogen-activated protein (map) kinases, c-jun nh2-terminal kinase (jnk) and p38 map kinase, as well as transcription factor nuclear factor kappab (nf-kappab | SIGNOR-249514 |
Q9NRC8 | P04637 | 1 | deacetylation | down-regulates | 0.498 | We found that sirt7 interacts with p53 and efficiently deacetylates p53 in vitro, which corresponds to hyperacetylation of p53 in vivo. | SIGNOR-160539 |
Q13393 | P17252 | 0 | phosphorylation | up-regulates | 0.714 | Serine 2, threonine 147, and serine 561 were identified as phosphorylation sites of pld1 by pkcalpha in the cells. | SIGNOR-69938 |
Q9UHD9 | Q13148 | 2 | binding | down-regulates quantity by destabilization | 0.583 | Here, we describe a high affinity interaction between UBQLN2 and TDP-43 and demonstrate that overexpression of both UBQLN2 and TDP-43 reduces levels of both exogenous and endogenous TDP-43 in human H4 cells.|Consequently, these data suggest that UBQLN2 enhances the clearance of TDP-43 | SIGNOR-262112 |
O95278 | Q9UQK1 | 1 | dephosphorylation | up-regulates quantity by stabilization | 0.749 | We have recently described that the activity of R5/PTG is down-regulated by the laforin-malin complex, composed of a dual specificity phosphatase (laforin) and an E3-ubiquitin ligase (malin). We now demonstrate that phosphorylation of R5/PTG at Ser-8 by AMPK accelerates its laforin/malin-dependent ubiquitination and subsequent proteasomal degradation, which results in a decrease of its glycogenic activity. | SIGNOR-276239 |
P55157 | P04114 | 1 | lipidation | up-regulates activity | 0.793 | As ApoB is translated, it is lipidated by microsomal triglyceride transfer protein (MTP). MTP adds triglycerides to the nascent ApoB during its co-translational translocation into the lumen of the endoplasmic reticulum. | SIGNOR-252118 |
P35638 | Q13131 | 0 | phosphorylation | down-regulates activity | 0.265 | Here, we report that phosphorylation of CHOP at Ser30 by AMPKα1 triggers CHOP degradation resulting in reduced macrophage apoptosis and subsequent ameliorated plaque vulnerability in vivo. | SIGNOR-259864 |
P30307 | O14757 | 0 | phosphorylation | down-regulates quantity by destabilization | 0.85 | The signal for ubiquitination after uv and ir exposure is created by phosphorylation of cdc25a mediated by chk1 and chk2, respectively. Chk1 is a major kinase phosphorylating cdc25a (ser76/124) and cdc25c (ser216). | SIGNOR-163158 |
Q06124 | O60674 | 2 | dephosphorylation | up-regulates quantity by stabilization | 0.793 | We report that SHP-2 dephosphorylates tyrosine (Tyr-1007) of Jak2 kinase, a critical recruitment site for the ubiquitin ligase-associated inhibitory protein suppressor of cytokine signaling-1 (SOCS-1), thereby contributing to Jak2 stability. Inactivation of SHP-2 function by blocking receptor/SHP-2 association or by using a catalytically inactive mutant of SHP-2 led to a marked increase in Jak2 ubiquitination/degradation, Jak2 phosphorylation on Tyr-1007, and Jak2/SOCS-1 association | SIGNOR-248665 |
Q9GZU1 | P17612 | 0 | phosphorylation | down-regulates | 0.2 | The stimulatory effect of h89 on mcoln1 function was not observed when ser(557) and ser(559) were mutated to alanine residues, indicating that these two residues are essential for pka-mediated negative regulation of mcoln1. | SIGNOR-158946 |
P01213 | P41143 | 1 | chemical activation | up-regulates activity | 0.667 | Accordingly, for the OTDP, the binding affinity and activity of a large number of opiate compounds have been tested at μ-, δ-, and κ-opiate receptors. Binding studies were originally conducted in guinea pig brain membranes, and subsequent studies have been carried out in CHO cells transfected with human receptors. Table 7 shows a biochemical method for determining activity and potency of opioid compounds, stimulation of [35S]GTPγS binding in membranes from cells transfected with human μ, δ, or κ receptors. | SIGNOR-258415 |
Q14012 | P46527 | 1 | phosphorylation | up-regulates activity | 0.305 | We also demonstrate that i) CaMKI phosphorylates p27 at Thr157and Thr198 in human cells and at Thr170and Thr197in mouse cells to modulate its subcellular localization;|Collectively, these results suggest that CaMKI is involved in mediating G1 progression by promoting cyclin D1/cdk4 complex formation through site-specific p27 phosphorylation in human lung epithelia. | SIGNOR-261194 |
Q13309 | P36639 | 2 | binding | down-regulates quantity by destabilization | 0.253 | Here, we report that MTH1 is regulated by polyubiquitination mediated by the E3 ligase Skp2. In melanoma cells, MTH1 was upregulated commonly mainly due to its improved stability caused by K63-linked polyubiquitination. Although Skp2 along with other components of the Skp1-Cullin-F-box (SCF) ubiquitin ligase complex was physically associated with MTH1, blocking the SCF function ablated MTH1 ubiquitination and expression. Conversely, overexpressing Skp2-elevated levels of MTH1 associated with an increase in its K63-linked ubiquitination. | SIGNOR-272790 |
P11226 | P48740 | 2 | binding | up-regulates activity | 0.751 | The results (Fig. 3A) show that the anti-MBL antibody, in addition to binding MBL captures both MASP-1 and MASP-2|Our results emphasize the similarity between complement activation through the MBL, or 'MBLectin' pathway of the innate immune system and the classical pathway of complement activation (Fig. 5). | SIGNOR-263414 |
O75197 | O00755 | 2 | binding | up-regulates activity | 0.59 | 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-131900 |
P51452 | P28482 | 1 | dephosphorylation | down-regulates activity | 0.672 | Extracellular regulated kinases (ERK) 1 and ERK2 are authentic substrates for the dual-specificity protein-tyrosine phosphatase VHR. A novel role in down-regulating the ERK pathway.|Catalysis by VHR requires the native structure of ERK and is specific for tyrosine 185 of ERK2 | SIGNOR-248536 |
Q9NZQ7 | P51955 | 0 | phosphorylation | up-regulates quantity by stabilization | 0.2 | NEK2 interacts with PD-L1, phosphorylating the T194/T210 residues and preventing ubiquitin-proteasome pathway-mediated degradation of PD-L1 in ER lumen. | SIGNOR-277314 |
Q7L7X3 | Q9Y6E0 | 0 | phosphorylation | up-regulates activity | 0.2 | Thus, MST3 phosphorylates TAO1 and TAO2, enabling their association with Myosin Va. | SIGNOR-280140 |
O60885 | O60674 | 0 | phosphorylation | up-regulates quantity by stabilization | 0.324 | JAK2 induces tyrosine phosphorylation of BRD4 at Y97/Y98, resulting in BRD4 stabilization. | SIGNOR-277312 |
P49841 | P17252 | 0 | phosphorylation | down-regulates | 0.357 | Gsk3 is different from most kinases in that it is constitutively partially active and the most common regulatory mechanism is inhibition by phosphorylation of ser21 in gsk3_ or ser9 in gsk3_. This inhibitory phosphorylation can be mediated by several kinases, such as akt/protein kinase b (pkb), protein kinase c (pkc) and protein kinase a (pka). | SIGNOR-188581 |
P25942 | Q12933 | 2 | binding | up-regulates activity | 0.844 | Cd40, a tumor necrosis factor receptor (tnfr) family member, forms a complex containing adaptor molecules traf2 and traf3. | SIGNOR-179473 |
P28482 | O43521 | 1 | phosphorylation | down-regulates quantity by destabilization | 0.716 | In vitro, bimel was phosphorylated by extracellular signal-regulated kinase on ser(69), which resides in the bimel-specific insert region. Using phosphospecific antibody against this site, we show that this residue is actually phosphorylated in cells. We also show that phosphorylation of ser(69) promotes ubiquitination of bimel. We conclude that mek inhibitors sensitize mda-mb231 and hbc4 cells to anoikis by blocking phosphorylation and hence degradation of bimel | SIGNOR-129874 |
P56704 | P11308 | 0 | transcriptional regulation | up-regulates quantity by expression | 0.2 | Interestingly, our data showed that ERG drastically induced Wnt ligand gene expression. | SIGNOR-261598 |
Q13257 | Q96SN8 | 0 | transcriptional regulation | up-regulates quantity by expression | 0.309 | These data indicate that CDK5RAP2 is a positive regulator of both the BUBR1 promoter and the MAD2 promoter | SIGNOR-260313 |
O60573 | Q9Y4X5 | 0 | ubiquitination | down-regulates quantity by destabilization | 0.678 | Human homologue of Drosophila ariadne (HHARI) is a RING-IBR-RING domain protein identified through its ability to bind the human ubiquitin-conjugating enzyme, UbcH7. Thus, by promoting the ubiquitin-mediated degradation of 4EHP, HHARI may have a role in both protein degradation and protein translation. | SIGNOR-268848 |
Q12774 | P61586 | 1 | guanine nucleotide exchange factor | up-regulates activity | 0.617 | 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-260533 |
Q7Z628 | Q13153 | 0 | phosphorylation | down-regulates activity | 0.249 | In this work we show that the Rac/Cdc42hs-regulated protein kinase PAK1 down-regulates the activity of the RhoA-specific guanine nucleotide exchange factor NET1. Specifically, PAK1 phosphorylates NET1 on three sites in vitro: serines 152, 153, and 538. Replacement of serines 152 and 153 with glutamate residues down-regulates the activity of NET1 as an exchange factor in vitro and its ability to stimulate actin stress fiber formation in cells. Using a phospho-specific antibody that recognizes NET1 phosphorylated on serine 152, we show that PAK1 phosphorylates NET1 on this site in cells and that Rac1 stimulates serine 152 phosphorylation in a PAK1-dependent manner. | SIGNOR-263018 |
O75116 | O14974 | 1 | phosphorylation | down-regulates activity | 0.785 | Rho kinase is known to control smooth muscle contractility by phosphorylating the 110 kDa myosin-targetting subunit (MYPT1) of the myosin-associated form of protein phosphatase 1 (PP1M). Phosphorylation of MYPT1 at Thr695 has previously been reported to inhibit the catalytic activity of PP1. Here, we show that the phosphorylation of Thr850 by Rho kinase dissociates PP1M from myosin, providing a second mechanism by which myosin phosphatase activity is inhibited. | SIGNOR-249164 |
Q13188 | P40763 | 1 | phosphorylation | down-regulates activity | 0.2 | Hippo pathway component MST2 kinase phosphorylates STAT3 at T622, which is located in the SH2 domain of STAT3. This phosphorylation blocks the SH2 domain in one STAT3 molecule to bind with the phosphorylated Y705 site in another STAT3 molecule, which further counteracts IL6-induced STAT3 dimerization and activation. | SIGNOR-277599 |
Q07889 | P27361 | 0 | phosphorylation | down-regulates | 0.636 | For example, inactivation of sos through phosphorylation by the downstream mapk | SIGNOR-26338 |
Q00535 | Q16555 | 1 | phosphorylation | down-regulates activity | 0.655 | Cdk5 and DYRK2 phosphorylate CRMP2 and CRMP4, respectively, priming these proteins at S522 before their subsequent phosphorylation by GSK-3b at T509, T516 and S518|e CRMP2 phosphorylation by GSK-3b disrupts its interaction with tubulin (Yamashita & Goshima, 2012), leading to growth inhibition | SIGNOR-264838 |
Q9BYB0 | P12814 | 1 | relocalization | up-regulates activity | 0.2 | SHANK proteins are ‘master’ scaffolding proteins that tether and organize intermediate scaffolding proteins. They are located at excitatory synapses, where they are crucial for proper synaptic development and function. SAPAP proteins subsequently bind to the PDZ domain of members of the SHANK protein family. SHANK proteins then bind to the actin cytoskeleton and to Homer protein, which in turn interacts with mGluRs. Through these extended links, PSD95, SAPAP, SHANK and Homer proteins form a quaternary complex that brings together mGluR and NMDAR complexes in the PSD (FIG. 3). | SIGNOR-264585 |
Q16539 | P18031 | 0 | dephosphorylation | down-regulates activity | 0.443 | Here, we show that PTP1B regulates CD40 and BAFF-R signaling and dephosphorylates the mitogen-activated protein kinase p38.|Specifically, PTP1B counteracts p38 mitogen-activated protein kinase activation by directly dephosphorylating Tyr182 of this kinase. | SIGNOR-277167 |
Q6IA17 | P49841 | 0 | phosphorylation | down-regulates quantity by destabilization | 0.2 | Activation of GSK3beta promotes Sigirr degradation in the proteasome .|Taken together, IL-37-induced Sigirr internalization is dependent on phosphorylation of Sigirr in T372 residue by GSK3\u03b2. | SIGNOR-279053 |
Q02952 | P17252 | 1 | relocalization | up-regulates activity | 0.459 | A-kinase-anchoring protein 250 (AKAP250; gravin) acts as a scaffold that binds protein kinase A (PKA), protein kinase C and protein phosphatases, associating reversibly with the beta(2)-adrenergic receptor. | SIGNOR-271836 |
P38405 | Q96P68 | 2 | binding | up-regulates activity | 0.2 | Here we systematically quantified ligand-induced interactions between 148 GPCRs and all 11 unique G alpha subunit C-termini. For each receptor, we probed chimeric G alpha subunit activation via a transforming growth factor-alpha (TGF alpha) shedding response in HEK293 cells lacking endogenous Gq/11- and G12/13- signaling. | We defined positive coupling if any member of the subfamily scored LogRAi ≥ -1 and negative coupling if all of the members scored LogRAi < -1 (Figure 3A-B). ROC analysis gives AUC = 0.78 (Figure S4A) when considering high-confidence known coupling data and suggested a threshold of LogRAi ≥ -1.0 for defining true couplings. | The score associated to this interaction has a LogRAi ≥ -1.0. | SIGNOR-256913 |
P49841 | Q08050 | 1 | phosphorylation | down-regulates quantity by destabilization | 0.355 | GSK3 phosphorylates FoxM1 on serine 474 which induces FoxM1 ubiquitination mediated by FBXW7. | SIGNOR-277208 |
P28358 | O00470 | 2 | binding | up-regulates activity | 0.375 | We now show that the Hoxa-9 protein physically interacts with Meis1 proteins. Hox proteins from the other AbdB-like paralogs, Hoxa-10, Hoxa-11, Hoxd-12, and Hoxb-13, also form DNA binding complexes with Meis1b. DNA binding complexes formed by Meis1 with Hox proteins dissociate much more slowly than DNA complexes with Meis1 alone, suggesting that Hox proteins stabilize the interactions of Meis1 proteins with their DNA targets. | SIGNOR-241226 |
P35637 | P78352 | 1 | post transcriptional regulation | up-regulates quantity | 0.27 | These results point toward a novel mechanism by which FUS targets neuronal mRNA and given that these PSD-95 and Shank1 3'-UTR G quadruplex structures are also targeted by the fragile X mental retardation protein (FMRP), they raise the possibility that FUS and FMRP might work together to regulate the translation of these neuronal mRNA targets.|As seen in Figure 7 (top panel), both PSD-95 Q1-Q2 and Shank1a GQ probes pulled down endogenous FUS, whereas their M2 mutants did not, indicating that the GQ structure is sufficient for recognition. | SIGNOR-262103 |
P06239 | P43405 | 0 | phosphorylation | down-regulates activity | 0.592 | Our experiments indicate that the TCR-induced activation of Erk2 depends on the function of SH2 domain of Lck and is reduced by phosphorylation of wild type Lck at Tyr192 or by mutation of this site to a negatively charged amino acid. Such dependence on the SH2 domain has also been reported for the bulk of TCR-induced tyrosine phosphorylation and activation of the interleukin 2 gene (26). Thus, phosphorylation of Lck at Tyr192 may represent a negative feedback mechanism in the interplay between Src and Syk family PTKs in TCR signaling | SIGNOR-246562 |
Q9Y6K1 | P68400 | 0 | phosphorylation | down-regulates activity | 0.2 | This modulation can be directly attributed to CK2-mediated phosphorylation of Dnmt3a. We also find that CK2-mediated phosphorylation is required for localization of Dnmt3a to heterochromatin. | SIGNOR-276650 |
Q5T447 | Q9UNK0 | 1 | polyubiquitination | down-regulates quantity by destabilization | 0.44 | Our co-immunoprecipitation experiments show that Syntaxin 8 directly interacts with HECTd3 and that the overexpression of HECTd3 promotes the ubiquitination of Syntaxin 8. Immunoprecipitates probed with the anti-ubiquitin (Santa Cruz) antibody could be recognized by the anti-ubiquin antibody (Fig. 3a), indicating that the shift of the His-syntaxin 8 protein bands were caused by polyubiquitin conjugations. Our data suggest that HECTd3 may function as an E3 ubiquitin-protein ligase to promote the ubiquitination and degradation of Syntaxin 8 through the proteasome pathway. | SIGNOR-271772 |
Q96CV9 | Q8WV16 | 2 | binding | up-regulates activity | 0.2 | DCAF4-mediated ubiquitination of OPTN facilitates the degradation of DBR-exposed SOD1. OPTN is involved in degradation of DBR-exposed SOD1. These data demonstrate that DCAF4-including CRL4 complex mediates OPTN ubiquitination at lysine 501, and this ubiquitination is absent in the ALS-related OPTNmut. | SIGNOR-272210 |
P04114 | P01130 | 2 | binding | up-regulates | 0.805 | In the case of ldl, binding of apolipoprotein b (apob) to the ldl-r18-20 and proteoglycans17 21 initiates plasma clearance and lipoprotein degradation | SIGNOR-87035 |
Q13501 | Q14596 | 2 | binding | up-regulates | 0.472 | Nbr1 and p62 interact and form oligomers. | SIGNOR-184273 |
Q96F45 | Q08117 | 2 | binding | down-regulates activity | 0.2 | these results show that Grg5 can specifically interact with the C-terminus of Nolz1. these data suggest that Nolz1 functions as a repressor molecule, and that Grg5 interactions with Nolz1 serve to modulate Nolz1 repressor function. Mechanistically, Grg5 is known to modulate Grg co-repressor activity, raising the possibility that classical Grg proteins mediate Nolz1-dependent transcriptional repression. GalNolz1ΔC22 showed increased repressor activity compared with GalNolz1, consistent with the ability of Grg5 to modulate Nolz1 repressor function. | SIGNOR-261192 |
O43541 | Q9HCE7 | 2 | binding | up-regulates activity | 0.831 | Smad6 mediates Tbx6 ubiquitination and proteasomal degradation. Tbx6 forms a ternary complex with Smad6 and Smurf1. Here, we report that Tbx6 interacts directly with Smad6, an inhibitory Smad that antagonizes the BMP signal. This interaction is mediated through the Mad homology 2 (MH2) domain of Smad6 and residues 90-180 of Tbx6. We demonstrate that Smad6 facilitates the degradation of Tbx6 protein through recruitment of Smurf1, a ubiquitin E3 ligase. | SIGNOR-272786 |
Q8NEM2 | P04626 | 0 | phosphorylation | up-regulates activity | 0.2 | Blocking HER2 activation using trastuzumab effectively abolished EGF-induced nuclear localization of SHCBP1 in gastric cancer cells [7].|In addition, nuclear translocation of SHCBP1 is a downstream consequence of HER2 activation, which is dependent on phosphorylation of SHCBP1 at the Ser273 site. | SIGNOR-280009 |
P35869 | P04798 | 1 | transcriptional regulation | up-regulates quantity by expression | 0.684 | Kaempferol proved to be capable of inhibiting binding of agonist and agonist-induced formation of the AHR/ARNT DNA-binding complex and upregulation of the AHR target gene, CYP1A1. | SIGNOR-259909 |
P06213 | Q14451 | 2 | binding | up-regulates | 0.418 | Insulin induces the ir-grb7 interaction in cells expressing physiological levels of the proteins, suggesting that grb7 is implicated in insulin signaling. | SIGNOR-77153 |
O75581 | Q9H461 | 2 | binding | up-regulates activity | 0.755 | Ligands such as Wnt1, Wnt3a, and Wnt8 couple the seven-transmembrane domain receptor Frizzled (Fzd) and the single-membrane-spanning low-density receptor-related protein 5/6 (LRP5/6) to activate WntBeta-catenin signaling. | SIGNOR-169638 |
Q16514 | P17544 | 2 | binding | up-regulates activity | 0.515 | We show that overexpression of hsTAF12 potentiates ATF7-induced transcriptional activation through direct interaction with ATF7, suggesting that TAF12 is a functional partner of ATF7. | SIGNOR-225249 |
Q9Y4K3 | Q13404 | 2 | binding | up-regulates activity | 0.699 | We find that traf6, a ring domain protein, functions together with ubc13/uev1a to catalyze the synthesis of unique polyubiquitin chains linked through lysine-63 (k63) of ubiquitin | SIGNOR-83603 |
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