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 |
|---|---|---|---|---|---|---|---|
P15172 | P53778 | 0 | phosphorylation | up-regulates activity | 0.446 | We determined that p38-gamma directly phosphorylated MyoD on Ser199 and Ser200, which results in enhanced occupancy of MyoD on the promoter of myogenin together with markedly decreased transcriptional activity. Phosphorylation of MyoD by p38-γ directs the assembly of a repressive transcriptional complex at the Myogenin promoter. | SIGNOR-276273 |
P23443 | P03372 | 1 | phosphorylation | up-regulates | 0.595 | Serine 167 is the major phosphorylation site on the human estrogen receptor. Phosphorylation is mediated by casein kinase ii. | SIGNOR-34117 |
P06493 | Q13501 | 1 | phosphorylation | up-regulates | 0.343 | Here we show that cdk1 phosphorylates p62 in vitro and in vivo at t269 and s272, which is necessary for the maintenance of appropriate cyclin b1 levels and the levels of cdk1 activity necessary to allow cells to properly enter and exit mitosis. | SIGNOR-169012 |
P30408 | Q08345 | 2 | binding | up-regulates activity | 0.424 | Gao et al have demonstrated that in metastatic breast cancer cell, DDR1 interacts with cell surface Transmembrane 4 L Six Family Member 1 (TM4SF1) and regulates tumor dormancy and reactivation [3]. The interaction between DDR1 and TM4SF1 is collagen dependent and control Protein Kinase C Alpha (PKCa) mediated downstream JAK-STAT signaling pathway [3] (Figure 3). Interestingly the data also showed that TM4SF1 failed to interact with DDR2. | SIGNOR-272400 |
P07320 | P02511 | 2 | binding | up-regulates activity | 0.52 | Human gamma-crystallins are long-lived, unusually stable proteins of the eye lens exhibiting duplicated, double Greek key domains. The lens also contains high concentrations of the small heat shock chaperone alpha-crystallin, which suppresses aggregation of model substrates in vitro. Mature-onset cataract is believed to represent an aggregated state of partially unfolded and covalently damaged crystallins. The alphaB-crystallin oligomers formed long-lived stable complexes with their gammaD-crystallin substrates. These in vitro results provide support for protein unfolding/protein aggregation models for cataract, with alpha-crystallin suppressing aggregation of damaged or unfolded proteins through early adulthood but becoming saturated with advancing age. | SIGNOR-253621 |
Q02156 | Q5JXC2 | 1 | phosphorylation | up-regulates activity | 0.2 | Here, we show that EGF stimulation induces PKCε-dependent phosphorylation of migration and invasion inhibitory protein (MIIP) at Ser303; this phosphorylation promotes the interaction between MIIP and RelA in the nucleus, by which MIIP prevents histone deacetylase 6 (HDAC6)-mediated RelA deacetylation, and thus enhances transcriptional activity of RelA and facilitates tumor metastasis. | SIGNOR-273828 |
P17612 | Q13526 | 1 | phosphorylation | down-regulates activity | 0.2 | Pka and pkc readily phosphorylated pin1 and its ww domain in summary, we have demonstrated that phosphorylation of the pin1 ww domain on ser16 regulates its ability to function as a pser/thr-binding module. |To examine the importance of Ser16 of Pin1, it was mutated to Glu to mimic pSer, and the mutant Pin1S16E failed to bind mitotic phosphoproteins | SIGNOR-112164 |
P33032 | P63092 | 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 ‚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-256798 |
P29350 | P78314 | 1 | dephosphorylation | down-regulates | 0.57 | Shp-1 dephosphorylates 3bp2 and potentially downregulates 3bp2-mediated t cell antigen receptor signaling | SIGNOR-146508 |
P49768 | P45984 | 0 | phosphorylation | up-regulates | 0.376 | This jnk phosphorylation of ps1 at ser(319)thr(320) enhances the stability of the ps1 c-terminal fragment that is necessary for gamma-secretase activity. | SIGNOR-179676 |
P48029 | O60674 | 0 | relocalization | down-regulates activity | 0.2 | Janus-activated kinase-2 (JAK2) participates in the regulation of the Na⁺-coupled glucose transporter SGLT1 and the Na⁺-coupled amino acid transporter SLC6A19. JAK2 is a novel regulator of the creatine transporter SLC6A8, which downregulates the carrier, presumably by interference with carrier protein insertion into the cell membrane. | SIGNOR-265781 |
P13861 | Q5VU43 | 2 | binding | up-regulates | 0.454 | Mmgl acts as a dual-specific akap by anchoring pka regulatory isoforms r1a and r2a. | SIGNOR-173831 |
O43586 | Q05209 | 0 | dephosphorylation | down-regulates activity | 0.61 | We also demonstrate that PTP-PEST dephosphorylates PSTPIP at tyrosine 344. Importantly, we identified tyrosine 344 as the main phosphorylation site of PSTPIP by performing tryptic phosphopeptide maps. |The biological functions of the complexes formed between PSTPIP and SH2 domain-containing tyrosine kinases may be to transmit the signals from activated EGF and PDGF receptor.|Furthermore, we show that PSTPIP is phosphorylated downstream of the activated PDGF and EGF receptors. This phosphorylation of PSTPIP is most likely mediated by c-Abl | SIGNOR-248656 |
Q9UHA4 | P27361 | 2 | binding | up-regulates | 0.606 | A protein called mp1 (mek partner 1) was identified that bound specifically to mek1 and erk1 and facilitated their activation. When overexpressed in cultured cells, mp1 enhanced activation of erk1 and activation of a reporter driven by the transcription factor elk-1. | SIGNOR-59877 |
Q13705 | P08476 | 2 | binding | up-regulates activity | 0.787 | Activin binds directly to ActR-IIB, and this complex associates with ActR-IB, which does not bind ligand on its own. In the resulting complex, ActR-IB becomes hyperphosphorylated, and this requires the kinase activity of ActR-IIB. | SIGNOR-235142 |
Q9H6Z4 | P84022 | 1 | relocalization | down-regulates | 0.389 | Ranbp3 directly recognizes dephosphorylated smad2/3, which results from the activity of nuclear smad phosphatases, and mediates nuclear export of smad2/3 in a ran-dependent manner | SIGNOR-184608 |
Q6PCD5 | Q00987 | 2 | binding | up-regulates activity | 0.364 | RFWD3 is a positive regulator of p53 abundance and regulates the G1 checkpoint in response to IR. We found that an E3 ubiquitin ligase RFWD3 (RNF201/FLJ10520) forms a complex with Mdm2 and p53 to synergistically ubiquitinate p53 and is required to stabilize p53 in the late response to DNA damage. | SIGNOR-271945 |
Q14457 | P10415 | 2 | binding | down-regulates | 0.739 | In mammalian cells, the antiapoptotic protein, bcl-2, binds to beclin 1 during nonstarvation conditions and inhibits its autophagy function. | SIGNOR-156941 |
Q9UPS8 | Q01196 | 0 | transcriptional regulation | down-regulates quantity by repression | 0.2 | In healthy individual, RUNX1/FLI1 complex negatively regulates ANKRD26 gene expression in MKs. | SIGNOR-266069 |
Q9UJU2 | Q04724 | 2 | binding | down-regulates activity | 0.689 | Our data shows that Groucho/TLE repression requires two sites of interaction in LEF-1 and that a central, conserved amino acid sequence within the primary region (F S/T/P/xx y I/L/V) is critical. | SIGNOR-260109 |
P49841 | Q16555 | 1 | phosphorylation | down-regulates activity | 0.724 | Here, we showed that glycogen synthase kinase-3beta (gsk-3beta) phosphorylated crmp-2 at thr-514 and inactivated it | SIGNOR-133255 |
Q15915 | P10071 | 1 | relocalization | up-regulates | 0.358 | Co-expression of zic1 resulted in gli1 and gli3 proteins being translocated to the nucleus in varying levels | SIGNOR-105497 |
Q9UNE7 | Q9BXL7 | 1 | ubiquitination | up-regulates activity | 0.327 | Subsequently, the ubiquitination of CARMA1 catalyzed by STUB1 was identified as Lys 27 linked, which is important for CARMA1 mediated NF-kappaB activation. | SIGNOR-278720 |
P30291 | P63151 | 0 | dephosphorylation | up-regulates quantity by stabilization | 0.385 | Knockout of FAM122A results in activation of PP2A-B55α, a phosphatase that dephosphorylates the WEE1 protein and rescues WEE1 from ubiquitin-mediated degradation. in tumor cells with oncogene-driven replication stress, CHK1 can directly phosphorylate FAM122A, leading to activation of the PP2A-B55α phosphatase and increased WEE1 expression. | SIGNOR-266381 |
O43524 | P67775 | 0 | dephosphorylation | up-regulates | 0.402 | Protein phosphatase 2a reactivates foxo3a through a dynamic interplay with 14-3-3 and aktpp2a-mediated dephosphorylation of t32/s253 is required for dissociation of 14-3-3, nuclear translocation, and transcriptional activation of foxo3a. | SIGNOR-163680 |
P28482 | Q9NXR1 | 1 | phosphorylation | up-regulates activity | 0.374 | Moreover, both proteins were phosphorylated by Cdc2 and Erk2 in vitro. In the case of Nudel, the phosphorylation sites were also located in the S/TP motifs. Detailed mutagenesis study indicated that T219, S242, and T245 were phosphorylated by Cdc2, while T219 and T245 were phosphorylated by Erk2.|Phosphorylation of Nudel in M phase appears to positively modulate dynein motor activity. Both phosphorylated and unphosphorylated forms of Nudel were transported by dynein (Fig. 7 and 9 and data not shown), indicating that neither of them inactivated the dynein motor. On the other hand, both phospho-Nudel and Nudelpmt5 bound Lis1 more strongly than Nudel or Nudelmt5 did | SIGNOR-249422 |
Q01130 | Q92993 | 0 | acetylation | down-regulates | 0.466 | In this study, we provide the first evidence that the acetyltransferase tip60 acetylates srsf2 on its lysine 52 residue inside the rna recognition motif, and promotes its proteasomal degradation. | SIGNOR-170594 |
Q04656 | P31751 | 0 | phosphorylation | up-regulates quantity by stabilization | 0.261 | Akt2 (Protein Kinase B Beta) Stabilizes ATP7A, a Copper Transporter for Extracellular Superoxide Dismutase, in Vascular Smooth Muscle: Novel Mechanism to Limit Endothelial Dysfunction in Type 2 Diabetes Mellitus|Immunoprecipitation, in vitro kinase assay, and mass spectrometry analysis reveal that insulin stimulates Akt2 binding to ATP7A to induce phosphorylation at Ser1424/1463/1466 | SIGNOR-272268 |
P16144 | O00329 | 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 |
P09651 | P62995 | 1 | transcriptional regulation | up-regulates quantity by expression | 0.699 | HnRNPA1 interacts with G-quadruplex in the TRA2B promoter and stimulates its transcription in human colon cancer cells. | SIGNOR-262280 |
Q9Y2H1 | Q9Y6E0 | 0 | phosphorylation | up-regulates | 0.441 | Ndr1/ndr2 protein kinase is activated by phosphorylation on the activation loop phosphorylation site ser281/ser282 and the hydrophobic motif phosphorylation site thr444/thr442. Autophosphorylation of ndr is responsible for phosphorylation on ser281/ser282, whereas thr444/thr442 is targeted by an upstream kinase. Here we show that mst3, a mammalian ste20-like protein kinase, is able to phosphorylate ndr protein kinase at thr444/thr442. In vitro, mst3 selectively phosphorylated thr442 of ndr2, resulting in a 10-fold stimulation of ndr activity. | SIGNOR-142510 |
P40763 | Q00535 | 0 | phosphorylation | up-regulates | 0.402 | We report here that the cdk5/p35 complex associates with stat3 and phosphorylates stat3 on the ser-727 residue in vitro and in vivo. Ser phosphorylation of stat3 and transcription of stat3 target genes, such as c-fos and junb, in a cdk5-dependent manner. | SIGNOR-124325 |
P42345 | P08069 | 1 | phosphorylation | up-regulates activity | 0.494 | Both recombinant mTOR and immunoprecipitated mTORC2 phosphorylate IGF-IR and InsR on Tyr1131/1136 and Tyr1146/1151, respectively.|Here we show that mTOR possesses unexpected tyrosine kinase activity and activates IGF-IR/InsR. | SIGNOR-280044 |
Q8TEU7 | P01112 | 1 | guanine nucleotide exchange factor | up-regulates | 0.336 | Gefs catalyse the transition from gdp-bound, inactive ras to gtp-bound, active ras. | SIGNOR-183796 |
P09341 | Q9P212 | 2 | binding | up-regulates | 0.2 | In the non-canonical wnt pathway, frizzled uses galfaq or galfai and gbetagamma dimers to activate phospholipase c (plc), resulting in protein kinase c (pkc) activation and calcium mobilization that regulates the transcription factor nfat, and frizzled also signals through the small gtpases rho and rac to c-jun n-terminal kinase (jnk), which activates the ap1 transcription factor. | SIGNOR-152591 |
Q9Y5H9 | Q9Y5G7 | 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-265694 |
Q13554 | Q13554 | 2 | phosphorylation | up-regulates activity | 0.2 | Ca2+/calmodulin-dependent protein kinase II: identification of threonine-286 as the autophosphorylation site in the alpha subunit associated with the generation of Ca2+-independent activity. | SIGNOR-250640 |
Q16539 | Q8IW41 | 1 | phosphorylation | up-regulates activity | 0.637 | In hela cells, prak was activated in response to cellular stress and proinflammatory cytokines. Prak activity was regulated by p38alpha and p38beta both in vitro and in vivo and thr182 was shown to be the regulatory phosphorylation site. | SIGNOR-58135 |
P46934 | Q9Y4H2 | 1 | ubiquitination | up-regulates activity | 0.374 | Nedd4 monoubiquitinates IRS-2, which promotes its association with Epsin1, a ubiquitin binding protein. | SIGNOR-278659 |
Q99538 | Q9Y4K3 | 0 | polyubiquitination | up-regulates quantity by stabilization | 0.307 | We demonstrate that TRAF6 ubiquitinates the proform of AEP through K63-linked polyubiquitin, reversible by USP17, and forms a complex with HSP90α to subsequently promote pro-AEP intracellular stability as well as secretion. We now present evidence that AEP is a substrate for TRAF6 ubiquitination, resulting in AEP/TRAF6/HSP90α complex formation. | SIGNOR-272853 |
O94901 | Q5MJ70 | 2 | binding | up-regulates activity | 0.247 | In this study, we found that SUN1 not only interacted with TERB1 but also interacted with MAJIN, and the interaction of SUN1 with MAJIN is stronger than TERB1. We also found that SUN1 interacted with SPDYA, an activator of CDK2. | Taken together, we speculate that speedy A is likely capable of interacting with both telomeres and the LINC complex and thus might function as the missing linkage between telomeres and the LINC complex during prophase I, stabilizing the telomere–NE connection | SIGNOR-263301 |
Q96P20 | Q8N4C8 | 0 | phosphorylation | up-regulates activity | 0.2 | MINK1-mediated NLRP3 phosphorylation at Ser725 is critical for inflammasome activation.|These results suggest that MINK1 promotes NLRP3 inflammasome activation via direct interaction with NLRP3.|To determine whether MINK1 phosphorylated NLRP3 directly, we used Phos-tag SDS\u2013PAGE to detect the phosphorylation of NLRP3. | SIGNOR-280042 |
Q9UIG0 | P45984 | 0 | phosphorylation | up-regulates | 0.2 | Wstf, a specific component of two chromatin remodeling complexes (swi/snf-type winac and iswi-type wich), was phosphorylated by the stimulation of mapk cascades in vitro and in vivo. Ser-158 residue in the wac (wstf/acf1/cbpq46) domain, located close to the n terminus of wstf, was identified as a major phosphorylation target | SIGNOR-188168 |
Q15788 | Q8IXJ9 | 2 | binding | up-regulates activity | 0.283 | We also show that ASXL1 associates specifically with SRC-1 and cooperates synergistically in the transcriptional activation.Therefore, both the ability to bind SRC-1 and the autonomous activation of ASXL1 are required for its coactivator function. Further data indicated that the transactivation domain (AD; amino acids 300–655) of ASXL1, newly defined in this study, interacts with the C-terminal AD2 (amino acids 1217–1441) of SRC-1, suggesting that one AD cooperates with the other AD in transcriptional activation by RAR. | SIGNOR-255924 |
P00533 | Q13237 | 0 | phosphorylation | down-regulates activity | 0.2 | Recombinant PKG II inhibited the epidermal growth factor (EGF)-induced activation of the EGF receptor via phosphorylating the T406 of the extracellular domain and blocked EGF-triggered proliferation of various cancer cells. | SIGNOR-277589 |
Q9UNE7 | P54252 | 1 | ubiquitination | down-regulates quantity by destabilization | 0.51 | Although our data show that CHIP may associate with Atx3 to ubiquitinate Atx3 in vitro, we still wonder whether CHIP is directly involved in the degradation of Atx3.|As a result, silencing of CHIP significantly increases the amount of Atx3 (XREF_FIG), suggesting that CHIP may down-regulate the Atx3 level. | SIGNOR-278667 |
P56945 | P06241 | 0 | phosphorylation | up-regulates activity | 0.766 | Taken together, these results suggest that p130Cas is directly phosphorylated by Fyn kinase in the cytoplasm of oligodendrocytes. | SIGNOR-279372 |
P33993 | P07948 | 0 | phosphorylation | up-regulates activity | 0.453 | Lyn phosphorylates MCM7 at Y600.|These evidences suggest that Lyn mediated Y600 phosphorylation may regulate MCM7 function in DNA replication licensing. | SIGNOR-278407 |
O60330 | 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-265698 |
P17612 | P08670 | 1 | phosphorylation | down-regulates activity | 0.309 | Ser-46 was phosphorylated preferentially by cAMP-dependent protein kinase. Both kinases reacted with Ser-6, Ser-24, Ser-38, Ser-50, and Ser-65. Domain- and sequence-specific phosphorylation of vimentin induces disassembly of the filament structure. | SIGNOR-250068 |
O15350 | P00519 | 0 | phosphorylation | up-regulates | 0.754 | C-abl phosphorylates p73 on a tyrosine residue at position 99 both in vitro and in cells that have been exposed to ionizing radiation. Our results show that c-abl stimulates p73-mediated transactivation and apoptosis. | SIGNOR-68931 |
O60353 | P41221 | 2 | binding | up-regulates activity | 0.698 | Human wnt5a, wnt5b and wnt11 are non-canonical wnt ligands transducing pcp signals through fzd3 or fzd6 receptors. | SIGNOR-141437 |
P16144 | Q9Y490 | 2 | binding | up-regulates activity | 0.494 | Over the past 10 years, the binding of talin to the cytoplasmic tail of integrin-β subunits has been established to have a key role in integrin activation. Binding of the phosphotyrosinebinding (PTB)-domain-like subdomain of the protein 4.1, ezrin, radixin, moesin (FERM) domain of talin to the conserved WxxxNP(I/L)Y motif of the β-integrin tail permits additional weaker interactions between talin and the membrane-proximal region of the tail that trigger integrin activation, probably through the disruption of inhibitory interactions between α- and β-subunit cytoplasmic tails. | SIGNOR-257627 |
P49841 | P56524 | 1 | phosphorylation | down-regulates | 0.364 | The double mutation of serines 298/302 into alanines, but also the sole mutation of serine 302, abolishes hdac4 phosphorylation by gsk3_we have shown that cells lacking gsk3_ are unable to degrade hdac4 after serum starvation | SIGNOR-170144 |
P28482 | Q99967 | 1 | phosphorylation | up-regulates activity | 0.454 | CITED2 coactivation is enhanced by activation of MAPK1 and requires T166.|CITED2 is phosphorylated by MAPK1 at S85, T166 and T175. | SIGNOR-278410 |
P17612 | O60825 | 1 | phosphorylation | up-regulates activity | 0.444 | PFK-2 that was phosphorylated on Ser466, but not Ser483, by PKA did not bind to 14-3-3s‚ | SIGNOR-250025 |
Q9Y297 | Q53EL6 | 1 | ubiquitination | down-regulates | 0.425 | Both akt and p70(s6k) phosphorylate pdcd4, allowing for binding of the e3-ubiquitin ligase beta-trcp and consequently ubiquitylation. | SIGNOR-160985 |
Q06124 | Q08881 | 1 | dephosphorylation | down-regulates activity | 0.324 | Using genetic and pharmacological approaches, we discovered that SHP2 dephosphorylates ITK specifically downstream of PD-1 and that this event was associated with PD-1 inhibitory cellular functions. | SIGNOR-277174 |
P01112 | Q9P212 | 0 | guanine nucleotide exchange factor | up-regulates | 0.578 | The presence of a rasgef motif in the n terminus of plcepsilon suggests that plcepsilon can activate ras by acting as an exchange factor by promoting the exchange of gtp for bound gdp. | SIGNOR-82859 |
P50539 | P14635 | 1 | transcriptional regulation | down-regulates quantity by repression | 0.266 | Mxi1 inhibits the proliferation of U87 glioma cells through down-regulation of cyclin B1 gene expression | Mxi1 inhibits the promoter activity of the cyclin B1 gene. | SIGNOR-266064 |
P19883 | O14793 | 2 | binding | down-regulates activity | 0.726 | Follistatin (FST) is a member of the tissue growth factor beta family and is a secreted glycoprotein that antagonizes many members of the family, including activin A, growth differentiation factor 11, and myostatin. FST315-deltaHBS-Fc induced improvements in muscle repair after injury/atrophy by modulating the early inflammatory phase allowing for increased macrophage density, and Pax7-positive cells leading to an accelerated restoration of myofibers and muscle function. | SIGNOR-251717 |
O43684 | O43683 | 0 | relocalization | up-regulates activity | 0.943 | Spindle checkpoint protein Bub1 is required for kinetochore localization of Mad1, Mad2, Bub3, and CENP-E, independently of its kinase activity | SIGNOR-252019 |
P32238 | Q14344 | 2 | binding | up-regulates activity | 0.25 | Our studies indicate that CCK-A receptors inserted into NIH3T3 cells also activate RhoA through G12/13 | SIGNOR-278062 |
Q13304 | P50148 | 2 | binding | up-regulates activity | 0.385 | Here we systematically quantified ligand-induced interactions between 148 GPCRs and all 11 unique G alpha subunit C-termini. For each receptor, we probed chimeric G alpha subunit activation via a transforming growth factor-alpha (TGF alpha) shedding response in HEK293 cells lacking endogenous Gq/11- and G12/13- signaling. | We defined positive coupling if any member of the subfamily scored LogRAi ≥ -1 and negative coupling if all of the members scored LogRAi < -1 (Figure 3A-B). ROC analysis gives AUC = 0.78 (Figure S4A) when considering high-confidence known coupling data and suggested a threshold of LogRAi ≥ -1.0 for defining true couplings. | The score associated to this interaction has a LogRAi ≥ -1.0. | SIGNOR-257087 |
O43541 | P49116 | 2 | binding | down-regulates | 0.2 | Smad6 interacts with tak1 and tab1, and smad7 with tab1 | SIGNOR-112636 |
O43521 | P27361 | 0 | phosphorylation | down-regulates quantity by destabilization | 0.731 | 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-129878 |
P49840 | Q07869 | 1 | phosphorylation | up-regulates activity | 0.2 | GSK-3alpha phosphorylates PPARalpha at Ser280, located in the ligand binding domain.|These results suggest that GSK-3alpha positively regulates PPARalpha activity through Ser280 phosphorylation. | SIGNOR-278515 |
P49770 | P49841 | 2 | binding | down-regulates | 0.2 | Akt also promotes protein synthesis by phosphorylating and inactivating gsk3b, thus releasing the gsk3b-dependent inhibition of the eukariotic translation initiation factor 2b (eif2b). | SIGNOR-175475 |
P06493 | Q9Y6I3 | 1 | phosphorylation | down-regulates activity | 0.323 | Phosphorylation of POB1 and Epsin by p34cdc2 kinase. Their phosphorylation sites (Ser411 of POB1 and Ser357 of Epsin) were determined. Phosphorylated Epsin and EpsinS357D formed a complex with α-adaptin less efficiently than wild type Epsin. | SIGNOR-262723 |
Q9H1D0 | P18031 | 0 | dephosphorylation | down-regulates activity | 0.631 | In HEK293 cells, transfected with the Ca2+ channel protein TRPV6, Ca2+ influx is increased and TRPV6 is tyrosine phosphorylated following addition of the tyrosine phosphatase inhibitor|PTP1B interacts with the N-terminal domain of TRPV6 within a region of amino acids 1-191 as shown by co-immunoprecipitation, bimolecular fluorescence complementation and the yeast 2-hybrid system. Point mutation of both tyrosines 161 and 162 in the TRPV6 protein abolishes the DMHV-effect on Ca2+ influx and tyrosine phosphorylation by Src. Single mutations of Y161 or Y162 shows that each of both tyrosines alone is sufficient for the DMHV-effect. We conclude that phosphorylation/dephosphorylation of tyrosines in position 161 and 162 is essential for regulation of Ca2+ influx through TRPV6 Ca2+ channels in HEK293 cells. | SIGNOR-248433 |
P00519 | O15269 | 1 | phosphorylation | down-regulates | 0.2 | We demonstrated that the er-resident human protein serine palmitoyltransferase long chain-1 (sptlc1), which is the first enzyme of sphingolipid biosynthesis, is phosphorylated at tyr(164) by the tyrosine kinase abl. this occurred through the specific abl-mediated phosphorylation of sptlc1 on tyr164, leading to the attenuation of its activity. | SIGNOR-202003 |
P28482 | Q13115 | 0 | dephosphorylation | down-regulates activity | 0.762 | Dephosphorylation and Inactivation of ERKs|A single protein kinase, MEK, activates ERK2 by phosphorylating threonine 183 and tyrosine 185 | SIGNOR-248718 |
P23443 | Q9UD71 | 1 | phosphorylation | up-regulates activity | 0.257 | D1R-PKA appears intact and elevated DARPP-32(pT34) in Rheb(S16H) mice is reduced by S6K1 inhibition (Figure 3).|S6K1 directly phosphorylates DARPP-32. | SIGNOR-279654 |
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 |
P32239 | P63092 | 2 | binding | up-regulates activity | 0.264 | 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-256765 |
Q9H2X6 | Q13131 | 0 | phosphorylation | up-regulates activity | 0.2 | These results indicate that HIPK2 is a substrate of AMPKα2 in vitro and in vivo. Site-directed mutagenesis of Thr112 and Ser114 in the N terminus, and Thr1107 in the C terminus markedly reduced HIPK2 phosphorylation by AMPKα2 in vitro (Figure S5J). | SIGNOR-276469 |
Q9Y4K3 | Q13546 | 2 | binding | up-regulates activity | 0.66 | Collectively, TRIF forms a multiprotein signaling complex along with TRAF6, TRADD, Pellino-1 and RIP1 for the activation of TAK1, which in turn activates the NF-_B and MAPK pathways. | SIGNOR-216325 |
Q9UPP1 | Q92547 | 2 | binding | up-regulates quantity by stabilization | 0.2 | TopBP1 Interacts with PHF8 through residue R1314 of TopBP1. Importantly, PHF8 regulates TopBP1 protein level by preventing its ubiquitination and degradation mediated by the E3 ligase UBR5. | SIGNOR-273657 |
P29474 | P0DP23 | 2 | binding | up-regulates activity | 0.76 | Electrons flow from the C-terminal reductase domain of one NOS monomer to the N-terminal oxygenase domain of the other NOS monomer (Siddhanta et al., 1998). The primary mode of enzyme activation is the binding of calcium-bound calmodulin to the N-terminal CaM-binding domain. This facilitates a structure change and the flow of electrons from NADPH through the flavins to the oxygenase domain of the other eNOS monomer | SIGNOR-251615 |
O15530 | P30559 | 1 | phosphorylation | up-regulates activity | 0.2 | We found that Ser261 in OXTR was phosphorylated by protein kinase D1 (PKD1).|In HEK293A cells, the PKD1-mediated phosphorylation of OXTR promoted its binding to Gq protein and, in turn, OXTR-mediated phosphorylation of PKD1, indicating a positive feedback loop. | SIGNOR-268577 |
Q9HBH9 | Q16539 | 0 | phosphorylation | up-regulates | 0.415 | Erk and p38 phosphorylate mnk1 and mnk2, which stimulates their in vitro kinase activity | SIGNOR-48349 |
Q96P48 | P63000 | 1 | gtpase-activating protein | down-regulates activity | 0.455 | 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-260451 |
P46379 | P35558 | 1 | acetylation | down-regulates quantity by destabilization | 0.34 | These results indicate that BAT3 and P300 can both exist in the PEPCK1 protein complex, suggesting the possibility that BAT3 could be an enhancer of PEPCK1 acetylation. | indicating a synergistic effect of BAT3 and P300 to promote PEPCK1 acetylation. | SIGNOR-267598 |
Q8N9B5 | Q8N0Z6 | 2 | binding | up-regulates activity | 0.531 | DNA damage activates ATM kinase which then phosphorylates Strap at Ser 203 (red circles). Phosphorylated Strap is stabilized and undergoes nuclear accumulation where it assembles into a co-activator complex, which includes p300 and cofactors such as JMY | SIGNOR-262647 |
O14733 | Q7Z6J0 | 2 | binding | up-regulates | 0.329 | We confirmed that posh binds activated rac1 and find that it also binds all mlk family members tested and interacts with mkk4/7 as well as jnk1 and jnk2. | SIGNOR-96955 |
Q92918 | P46108 | 2 | binding | up-regulates | 0.686 | We found that hpk1 interacted with crk and crkl adaptor proteins in vitro and in vivo and that the proline-rich motifs within hpk1 were involved in the differential interaction of hpk1 with the crk proteins and grb2. Crk and crkl not only activated hpk1 but also synergized with hpk1 in the activation of jnk. | SIGNOR-63988 |
P30622 | Q38SD2 | 0 | phosphorylation | up-regulates activity | 0.398 | LRRK1 phosphorylates CLIP-170 at Thr1384, located in its C-terminal zinc knuckle motif, and this promotes the association of CLIP-170 with dynein-dynactin complexes. | SIGNOR-275469 |
P55211 | Q13627 | 0 | phosphorylation | down-regulates activity | 0.388 | Depletion of DYRK1A from human cells by short interfering RNA inhibits the basal phosphorylation of caspase 9 at an inhibitory site, Thr125. DYRK1A-dependent phosphorylation of Thr125 is also blocked by harmine, confirming the use of this beta-carboline alkaloid as a potent inhibitor of DYRK1A in cells.|When co-expressed in cells, DYRK1A interacts with caspase 9, strongly induces Thr125 phosphorylation and inhibits caspase 9 auto-processing. | SIGNOR-279326 |
P63096 | Q99835 | 2 | binding | up-regulates | 0.516 | Consistent with its predicted topology, smo couples to a specific family of inhibitory g protein (gis) to regulate hh signaling. | SIGNOR-199159 |
O95837 | O43614 | 2 | binding | up-regulates activity | 0.435 | 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-257290 |
P54829 | Q16539 | 2 | binding | up-regulates | 0.489 | First [] step prevents upstream activating kinases from promiscuously binding and activating p38a. Second, by blocking access to the mapk insert pocket, through the stepcat interaction, step can prevent the binding of allosteric signaling molecules that induce autoactivation of p38a. | SIGNOR-194829 |
P11309 | Q00987 | 1 | phosphorylation | up-regulates | 0.388 | Additionally, the pim kinases phosphorylate mdm2 in vitro and in cultured cells at ser166 and ser186, two previously identified targets of other signaling pathways, including akt. | SIGNOR-178619 |
O43490 | Q15262 | 0 | dephosphorylation | down-regulates activity | 0.2 | PTPRK dephosphorylates CD133, which is a stem cell marker; phosphorylated CD133 accelerates xenograft tumor growth of colon cancer cells through the activation of AKT, but the functional significance of this has remained elusive.|Together, these observations suggest that PTPRK suppresses CD133\u2010mediated colon cancer growth both in\u00a0vitro and in\u00a0vivo. | SIGNOR-277133 |
Q9Y5S2 | P26038 | 1 | phosphorylation | up-regulates activity | 0.2 | In this study, we have shown that MRCKb phosphorylated moesin at Thr-558 | We have shown that the phosphorylation is important to the formation of ®lopodia, and that MRCK may regulate this formation through the phosphorylation of ERM proteins at the tip of ®lopodia. | SIGNOR-260802 |
P31751 | Q12778 | 1 | phosphorylation | down-regulates activity | 0.658 | Our results demonstrate that pkb/akt directly phosphorylates fkhr1, a member of the closely related fkhr subclass of the forkhead family of transcription factors, on at least two residues (threonine-24 and serine-253). These results indicate that phosphorylation by pkbyakt negatively regulates fkhr1 by promoting export from the nucleus. | SIGNOR-68652 |
O43524 | Q15831 | 1 | transcriptional regulation | down-regulates quantity | 0.634 | SGK-1 Negatively Regulates LKB1 Expression via FOXO3 Transcription Factor | SIGNOR-255758 |
Q6ZRV2 | P48730 | 2 | binding | up-regulates quantity | 0.326 | We identified members of the FAM83 family of proteins as partners of CK1 in cells. All eight members of the FAM83 family (FAM83A–H) interacted with the α and α-like isoforms of CK1; FAM83A, -B, -E, and -H also interacted with the δ and ε isoforms of CK1. The intrinsic catalytic activity of CK1 is not affected by or required for the association of CK1 with FAM83 proteins. Our findings imply that the DUF1669 domains of FAM83 proteins anchor CK1 α, α-like, δ, and ε isoforms in specific subcellular compartments and potentially mediate their association with substrates. | SIGNOR-273768 |
Q01726 | P42127 | 2 | binding | down-regulates activity | 0.739 | The antagonist agouti signal protein (ASP) interacts with the Mc1r and blocks its stimulation by MSH. | SIGNOR-252378 |
Q13470 | Q13470 | 2 | phosphorylation | up-regulates activity | 0.2 | We found a similar reduction in the levels of phosphorylation of Tyr277, which corresponds to the predicted major site of autophosphorylation within the activation loop of Tnk1 (Fig. 3C). | SIGNOR-274126 |
P08047 | Q04206 | 2 | binding | up-regulates | 0.63 | Rela (p65) nf-kappab subunit interacts with the zinc finger dna-binding domain of sp1. | SIGNOR-75004 |
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