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 |
|---|---|---|---|---|---|---|---|
Q16827 | P04626 | 1 | dephosphorylation | down-regulates quantity by destabilization | 0.403 | In this study, our co-immunoprecipitation experiment along with the results derived from in vivo , cultured cells and clinical specimen confirm that PTPRO dephosphorylates ERBB2 at Y1248.|PTPRO overexpression remarkably accelerated degradation of ERBB2 (XREF_FIG). | SIGNOR-276979 |
P06493 | P30260 | 1 | phosphorylation | up-regulates | 0.704 | Apc activation is thought to depend on apc phosphorylation and cdc20 binding. We have identified 43 phospho_sites on apc of which at least 34 are mitosis specific. Of these, 32 sites are clustered in parts of apc1 and the tetratricopeptide repeat (tpr) subunits cdc27, cdc16, cdc23 and apc7. In vitro, at least 15 of the... | SIGNOR-119873 |
Q96TA1 | P00533 | 0 | phosphorylation | up-regulates activity | 0.2 | We demonstrate here that activated EGFR phosphorylates the Y593 residue of the protein known as family with sequence similarity 129, member B (FAM129B), which is overexpressed in many types of human cancer. FAM129B phosphorylation increased the interaction between FAM129B and Ras, resulting in reduced binding of p120-... | SIGNOR-273637 |
Q9Y4K3 | Q07820 | 1 | ubiquitination | up-regulates activity | 0.396 | TRAF6 likely directly ubiquitinates MCL-1 since purified TRAF6 promoted the ubiquitination of recombinant GST-MCL-1 and co-expression of Tax with TRAF6 further enhanced MCL-1 ubiquitination .|Therefore, TRAF6 mediated MCL-1 stabilization appears to be a common mechanism of cell survival usurped by both viral and non vi... | SIGNOR-278726 |
Q16584 | Q92918 | 0 | phosphorylation | up-regulates | 0.574 | Hpk1 also phosphorylated mlk-3 activation loop in vitro, and ser281 was found to be the major phosphorylation site, indicating that hpk1 also activates mlk-3 via phosphorylation of the kinase activation loop. | SIGNOR-83415 |
P11802 | P24385 | 2 | binding | up-regulates | 0.964 | D-type cyclins (cyclin d1, d2, or d3) and their associated cyclin-dependent kinases (cdk4, cdk6) connect signals from cytokines to the cell cycle machinery, and they propel cells through the g1 restriction point and into the s phase when activated by cyclin d1, cdk4 is able to phosphorylate prb, | SIGNOR-201666 |
P06493 | Q5FBB7 | 1 | phosphorylation | up-regulates activity | 0.2 | The complex between shugoshin and protein phosphatase 2A (Sgo1-PP2A) localizes to centromeres in mitosis, binds to cohesin in a reaction requiring Cdk-dependent phosphorylation of Sgo1, dephosphorylates cohesin-bound sororin, and protects a centromeric pool of cohesin from mitotic kinases and the cohesin inhibitor Wapl... | SIGNOR-265263 |
Q96QV1 | Q15465 | 2 | binding | down-regulates activity | 0.897 | Hip encodes a membrane glycoprotein that binds to all three mammalian hedgehog proteins with an affinity comparable to that of ptc-1. our findings support a model in which hip attenuates hedgehog signalling as a result of binding to hedgehog proteins: a negative regulatory feedback loop established in this way could th... | SIGNOR-65078 |
P15923 | Q15759 | 0 | phosphorylation | up-regulates | 0.436 | Here we show that p38 mapk, whose activity is essential for myogenesis, regulates myod/e47 heterodimerization. Phosphorylation of e47 at ser140 by p38 induces myod/e47 association and activation of muscle-specific transcription, while the nonphosphorylatable e47 mutant ser140ala fails to heterodimerize with myod and di... | SIGNOR-134190 |
Q9H2G2 | Q99683 | 1 | phosphorylation | up-regulates | 0.253 | Induction of apoptosis by the ste20-like kinase slk, a germinal center kinase that activates apoptosis signal-regulating kinase and p38 | SIGNOR-142665 |
Q92748 | Q9NPA3 | 2 | binding | down-regulates activity | 0.512 | In the current study, we have determined the crystal structure of mouse S14 to 2.65-Å resolution. The structure of S14 reveals a helical protein arranged as a symmetric dimer. Cultured cell experiments indicate that S14 can form heterodimers with MIG12, suggesting a mechanism through which S14 could modulate ACC activi... | SIGNOR-267113 |
P50281 | P02679 | 1 | cleavage | down-regulates quantity by destabilization | 0.2 | Matrix metalloproteinases collagenase-2, macrophage elastase, collagenase-3, and membrane type 1-matrix metalloproteinase impair clotting by degradation of fibrinogen and factor XII| We have now investigated the role of collagenase-2 (MMP-8), macrophage elastase (MMP-12), collagenase-3 (MMP-13), and membrane type 1-mat... | SIGNOR-263616 |
Q01974 | P45983 | 2 | binding | up-regulates | 0.46 | Wnt5a stimulation induces activation of the c-jun n-terminal kinase jnk at the wound edge in a ror2-dependent manner, and inhibiting jnk activity abrogates wnt5a-induced lamellipodia formation and mtoc reorientation | SIGNOR-179671 |
P20393 | P37231 | 0 | transcriptional regulation | up-regulates quantity by expression | 0.277 | Mutations of the 5' or 3' half-sites of the response element totally abrogated PPARgamma binding and transcriptional activation, identifying this site as a novel type of functional PPARgamma response element. Finally, ectopic expression of Rev-Erbalpha in 3T3-L1 preadipocytes potentiated adipocyte differentiation induc... | SIGNOR-268022 |
O60674 | P18031 | 0 | dephosphorylation | down-regulates activity | 0.797 | Immunoblots with phospho-specific antibodies confirmed that PTP1B suppresses phosphorylation of the Jak2 activation site tyrosines (Y1007/Y1008) and Stat3 in a dose-dependent manner | SIGNOR-248405 |
Q99459 | P06493 | 0 | phosphorylation | up-regulates activity | 0.624 | Cdc5-dependent Net1 phosphorylation and Cdc14 release from the nucleolus require prior Cdc5 activation by Cdk1 and active separase to promote Cdc14 activation.|Cdk1 initially phosphorylates Cdc5, mostly at T242 and T238 (T242 phosphorylation is especially relevant based on our results), and phosphorylation activates it... | SIGNOR-279597 |
P18669 | Q13153 | 0 | phosphorylation | down-regulates | 0.2 | Activated pak1 inhibits glycolysis by association of its catalytic domain with pgam-b and subsequent phosphorylation of the enzyme on serine residues 23 and 118, thereby abolishing pgam activity. | SIGNOR-91594 |
Q96JP5 | Q99558 | 1 | ubiquitination | up-regulates | 0.5 | Zfp91 interacts with and promotes the lys(63)-linked ubiquitination of nik and subsequent processing of p100 to p52. | SIGNOR-167331 |
P33032 | Q03113 | 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- signali... | SIGNOR-257441 |
P60763 | O75398 | 0 | transcriptional regulation | up-regulates quantity by expression | 0.2 | Affymetrix gene profiling studies revealed Rac3 as a potential target gene and quantitative RT-PCR analysis confirmed that Rac3 was upregulated by Deaf-1 in immortalized mouse mammary epithelial cells. | SIGNOR-269059 |
P34925 | O14641 | 2 | binding | up-regulates | 0.419 | Ryk also binds to dishevelled, through which it activates the canonical wnt, providing a link between wnt and dishevelled. | SIGNOR-129571 |
Q04771 | Q13873 | 2 | binding | up-regulates | 0.714 | Bmpr-ii is a transmembrane serine/threonine kinase that binds bmp-2 and bmp-7 in association with multiple type i receptors, including bmpr-ia/brk1, bmpr-ib, and actr-i, which is also an activin type i receptor. | SIGNOR-33434 |
Q02763 | P42224 | 1 | phosphorylation | up-regulates activity | 0.301 | Tie2-R849W induced STAT1 phosphorylation at Y701 independent of ligand stimulation.|Together, Tie2-R849W induced functional activation of STAT1, leading to increased expression of STAT1-responsive gene like IRF1. | SIGNOR-279131 |
Q5TEC6 | Q9NRC8 | 0 | deacetylation | up-regulates activity | 0.2 | Besides confirming the previously reported histone H3K18 deacylation activity, our results revealed that SIRT7 has an astonishingly high activity to catalyze deacylation of H3K36 and is also catalytically active to deacylate H3K37. | SIGNOR-275883 |
P52789 | P01106 | 0 | transcriptional regulation | up-regulates quantity | 0.37 | Here, using the P493-6 Burkitt's lymphoma model with an inducible MYC, we demonstrate that HIF-1 cooperates with dysregulated c-Myc to promote glycolysis by induction of hexokinase 2, which catalyzes the first step of glycolysis, and pyruvate dehydrogenase kinase 1, which inactivates pyruvate dehydrogenase and diminish... | SIGNOR-259986 |
P17612 | P84243 | 1 | phosphorylation | up-regulates activity | 0.2 | Identification of a novel phosphorylation site on histone h3 coupled with mitotic chromosome condensation. | SIGNOR-70424 |
Q9UQL6 | Q13555 | 0 | phosphorylation | down-regulates | 0.428 | Camk phosphorylates serines -259 and -498 in hdac5, which subsequently serve as docking sites for 14-3-3. Our studies suggest that 14-3-3 binding to hdac5 is required for camk-dependent disruption of mef2hdac complexes and nuclear export of hdac5, and implicate 14-3-3 as a signal-dependent regulator of muscle cell diff... | SIGNOR-85102 |
Q9UBY5 | P38405 | 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- signali... | SIGNOR-256747 |
Q13555 | Q9Y618 | 1 | phosphorylation | down-regulates | 0.2 | The kinase activity of camkii was essential for the activation of notch signaling. We also determined that camkii could enhance the association between notch1-ic and rbp-jk. Furthermore, the physical association between rbp-jk and smrt was substantially suppressed by camkii. We demonstrated that camkii directly bound a... | SIGNOR-191777 |
Q9NZH5 | P06493 | 0 | phosphorylation | up-regulates activity | 0.291 | HPTTG is phosphorylated by Cdc2 at Ser165. we show that hPTTG is phosphorylated during mitosis. The direct phosphorylation of hPTTG by Cdc2 is interesting in itself since the substrates of this master mitotic kinase are supposed to play important roles in the initiation and progression of mitosis. | SIGNOR-262700 |
P04201 | P21333 | 2 | binding | up-regulates activity | 0.2 | We further determined that GPCRs, AT1R, and MAS directly recruited FLNa and promoted its phosphorylation by cellular S/T kinases in an agonist-dependent manner. Our studies thus provide a structural framework for filamin in GPCR signaling, potentially regulating a variety of cellular responses. MAS likely binds filamin... | SIGNOR-260627 |
Q9Y4D8 | P10275 | 1 | ubiquitination | down-regulates quantity by destabilization | 0.2 | We identified several E3 ligases as strong candidates responsible for AR and MYC protein loss as HECTD4, MYCBP2, and TRIM49. HECTD4 and MYCBP2 target AR and MYC for degradation while TRIM49 appears to promote AR and MYC stability. We have shown that these E3 ligases in turn are directly regulated by MYC. MYC in turn r... | SIGNOR-267148 |
Q14469 | Q8WTT2 | 1 | transcriptional regulation | down-regulates quantity | 0.2 | The expression level of FAD24 is inversely associated with that of HES1 in porcine MSCs after adipogenic induction. Enforced overexpression of HES1 in MSCs during the early stage of adipogenesis significantly repressed the transcription of FAD24 (P < 0.01) and the other pro-adipogenic genes | SIGNOR-253059 |
Q9Y490 | P16144 | 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 mo... | SIGNOR-257627 |
P40763 | Q05655 | 0 | phosphorylation | up-regulates | 0.596 | Abrogation of pkcdelta activity inhibited insulin-induced stat3 phosphorylation, pkcdelta-stat3 association and nuclear translocation. | SIGNOR-143828 |
Q9BW11 | P61244 | 2 | binding | up-regulates activity | 0.467 | the role MAX plays in transcription is thought to be primarily as a cofactor for DNA binding. In this capacity, however, it appears to be essential for most, if not all, the known biological activities of MYC. MAX also functions as a cofactor for DNA binding for a group of bHLHZip proteins related to MYC, including MNT... | SIGNOR-240393 |
O43865 | O15530 | 0 | phosphorylation | down-regulates activity | 0.2 | Residue 68 resides in a consensus phosphorylation site for PKD (Figure 1A) [22,23]. Interestingly, phosphorylation of Ser68 could allow for subsequent phosphorylation of Ser71, Ser74, Ser77 and Ser80 by CK1, for which the consensus phosphorylation site is pS/T-X-X-S/T| We found that phosphorylation of Ser71 and Ser74 w... | SIGNOR-249174 |
Q15306 | O15054 | 0 | transcriptional regulation | up-regulates quantity by expression | 0.422 | JMJD3 seems to function by controlling expression of the transcription factor IRF4, which in turn is required for M2 polarization of macrophages in vitro and in vivo. Although this pathway is strongly supported by genetic. | SIGNOR-249540 |
Q9H2K2 | O15234 | 1 | ADP-ribosylation | down-regulates quantity by destabilization | 0.2 | Here, we identify RNF146, a RING-domain E3 ubiquitin ligase, as a positive regulator of Wnt signalling. RNF146 promotes Wnt signalling by mediating tankyrase-dependent degradation of axin. Mechanistically, RNF146 directly interacts with poly(ADP-ribose) through its WWE domain, and promotes degradation of PARsylated pro... | SIGNOR-263382 |
Q7L7L0 | Q86Y13 | 0 | monoubiquitination | up-regulates activity | 0.2 | 2A-HUB catalyzes monoubiquitination of H2A at lysine 119, functioning as a combinatoric component of the repression machinery required for specific gene regulation programs. Thus, 2A-HUB mediates a selective repression of a specific set of chemokine genes in macrophages, critically modulating migratory responses to TL... | SIGNOR-271757 |
Q9UHD2 | Q04864 | 1 | phosphorylation | up-regulates | 0.579 | The present results demonstrate that ikkepsilon- and tbk1-mediated phosphorylation of crel in the c-terminal td leads to cytoplasmic dissociation of a crel-ikb_ complex and nuclear accumulation of crel. | SIGNOR-148623 |
Q96B86 | Q92859 | 2 | binding | down-regulates activity | 0.787 | Netrin-1-neogenin interactions mediate chemoattractive axon guidance, while RGMa-neogenin interactions repel axons. | SIGNOR-268388 |
P06241 | P16410 | 1 | phosphorylation | up-regulates quantity by stabilization | 0.77 | CTLA-4 can associate with the Src kinases Fyn and Lck and that transfection of Fyn or Lck, but not the unrelated kinase ZAP70, can induce tyrosine phosphorylation of CTLA-4 on residues Y201 and Y218.  Phosphorylation of CTLA-4 Y201 in Jurkat cells correlated with cell surface accumulation of CTLA-4. | SIGNOR-251161 |
Q13555 | P18846 | 1 | phosphorylation | up-regulates activity | 0.299 | Phosphopeptide mapping analysis and Western blotting studies demonstrated that in vitro, CaMK II phosphorylates only Ser63 (corresponding to Ser133 of CREB), which is essential for the activation, and not Ser72 (corresponding to Ser142 of CREB), which is a negative regulation site. | SIGNOR-250692 |
Q5S007 | Q9P2J5 | 1 | phosphorylation | down-regulates activity | 0.2 | In this study, we elucidated that leucyl-tRNA synthetase (LRS) was an LRRK2 kinase substrate and identified T293 as an LRRK2 phosphorylation site. LRRK2-meidated LRS phosphorylation or G2019S can lead to impairment of LRS editing, increased ER stress, and accumulation of autophagy markers. | SIGNOR-277417 |
Q12888 | P60510 | 0 | dephosphorylation | up-regulates activity | 0.357 | Here we show that 53BP1 is phosphorylated during mitosis on two residues, T1609 and S1618, located in its well-conserved ubiquitination-dependent recruitment (UDR) motif.|Dephosphorylation enables the recruitment of 53BP1 to double-strand DNA breaks |Depletion of PP4C, or PP4R3beta, causes persistence of phospho-T1609 ... | SIGNOR-264450 |
P02751 | P80370 | 2 | binding | up-regulates | 0.37 | We show a direct interaction of pref-1 and fibronectin via the pref-1 juxtamembrane domain and fibronectin c-terminal domain | SIGNOR-165347 |
P41134 | Q9UQM7 | 0 | phosphorylation | up-regulates activity | 0.2 | Here we show that CaMKII can directly phosphorylate Beclin 1 at Ser90 to promote K63-linked ubiquitination of Beclin 1 and activation of autophagy. | SIGNOR-277367 |
Q9Y4K3 | Q8IUC6 | 1 | polyubiquitination | up-regulates | 0.83 | Here, we show that the TRAF family proteins directly bind TICAM-1 and demonstrate that TRAF2 and TRAF6 bind different sites of the N-terminal TICAM-1 and accelerate its polyubiquitination. we speculate that polyubiquitination of TICAM-1 by TRAF2 and TRAF6 is required for TICAM-1 to induce IRF-3 and NF-κB activation. Th... | SIGNOR-271428 |
Q96EB6 | Q8N163 | 2 | binding | down-regulates activity | 0.745 | Here, we report that, in human cell lines, DNA damage triggered the phosphorylation of DBC1 on Thr454 by ATM (ataxia telangiectasia-mutated) and ATR (ataxia telangiectasia and Rad3-related) kinases. Phosphorylated DBC1 bound to and inhibited SIRT1, resulting in the dissociation of the SIRT1-p53 complex and stimulating... | SIGNOR-267663 |
P38936 | Q9NRM7 | 0 | phosphorylation | down-regulates quantity | 0.417 | Phosphorylation by Lats2 induces degradation of p21 and promotes apoptosis.|Subsequently, Lats2 phosphorylates p21 at S146. | SIGNOR-279530 |
Q16620 | Q9NR48 | 0 | transcriptional regulation | up-regulates quantity by expression | 0.2 | Depletion of ASH1L decreases neurite outgrowth and decreases expression of the gene encoding the neurotrophin receptor TrkB whose signaling pathway is linked to neuronal morphogenesis. | SIGNOR-269058 |
P06493 | P31350 | 1 | phosphorylation | down-regulates | 0.504 | We found that, during g2, following cdk-mediated phosphorylation of thr33, rrm2 is degraded via scf(cyclin f) to maintain balanced dntp pools and genome stability. | SIGNOR-197630 |
P17542 | P25791 | 2 | binding | up-regulates | 0.926 | Transcriptional activity of tal1 in t cell acute lymphoblastic leukemia (t-all) requires rbtn1 or -2 | SIGNOR-46161 |
P52926 | P06493 | 0 | phosphorylation | down-regulates | 0.374 | Architecture of high mobility group protein i-c dna complex and its perturbation upon phosphorylation by cdc2 kinase. Phosphorylation by cdc2 reduces binding strength of the mammalian and insect hmgi proteins to dna. After phosphorylation of the protein at ser-43 and ser-58 by cdc2 kinase multiple contacts of dbds, esp... | SIGNOR-74098 |
Q13464 | P17661 | 1 | phosphorylation | down-regulates | 0.316 | The sites phosphorylated by Aurora-B; Thr-7/Ser-13/Ser-38 of GFAP, and Thr-16 of desmin are common with those related to Rho-associated kinase (Rho-kinase), which has been reported to phosphorylate GFAP and desmin at cleavage furrow during cytokinesis. Rho-kinase was found to phosphorylate desmin at Thr-16, Thr-75, and... | SIGNOR-100177 |
O15162 | P12931 | 0 | phosphorylation | up-regulates activity | 0.476 | Plscr1 is phosphorylated by c-src, within the tandem repeat sequence 68vynqpvynqp77.|The EGF-mediated Interaction between PLSCR1 and Shc Requires Phosphorylation of Tyr69 and Tyr74 in PLSCR1 | SIGNOR-103773 |
P06493 | Q13541 | 1 | phosphorylation | down-regulates activity | 0.397 | Phosphorylation of 4e-bp1 is critical in causing its dissociation from eif-4e, leaving 4e available to form translationally active eif-4f complexes, switching on mrna translation. We show that the cyclin-dependent kinase, cdc2, phosphorylates 4e-bp1 at thr-70 and that phosphorylation of this site is permissive for ser-... | SIGNOR-110416 |
P08754 | Q99835 | 2 | binding | up-regulates | 0.429 | Consistent with its predicted topology, smo couples to a specific family of inhibitory g protein (gis) to regulate hh signaling. | SIGNOR-199165 |
Q4V328 | Q13233 | 2 | binding | up-regulates activity | 0.312 | To examine whether GRASP‐1 interacts with MEKK1 and JNK1 in neurons, co‐immunoprecipitation experiments were performed with detergent‐solubilized extracts from cultured cortical neurons. Both antiJNK1 and anti‐MEKK1 antibodies immunoprecipitated GRASP‐1 from neuronal lysates. These results suggest that GRASP‐1 interact... | SIGNOR-260640 |
O60674 | P19235 | 1 | phosphorylation | up-regulates activity | 0.812 | JAK2 in turn phosphorylates several tyrosine residues on the EpoR-cytosolic domain and probably on JAK2 itself that serve as docking sites for SH2 or protein tyrosine binding domains of downstream signal transduction proteins such as STAT5, phosphatidylinositol 3-kinase, Shc, and tyrosine phosphatases SHP1 and SHP2 | SIGNOR-251351 |
P40692 | P00519 | 0 | phosphorylation | up-regulates quantity by stabilization | 0.344 | We also observed phosphorylation of MLH1 by ABL1 in an in vitro kinase assay with purified recombinant ABL1 and MLH1, confirming there is a direct phosphorylation between ABL1 and the MLH1 component of the MLH1-PMS2 heterodimer.|we propose that ABL1 prevents MLH1 from being targeted for degradation by the chaperone Hsp... | SIGNOR-279581 |
P49768 | P42574 | 0 | cleavage | up-regulates activity | 0.454 | Remarkably, the caspases acting on PS1 could be subdivided in two groups. One group, containing caspase-8, -6 and -11, cleaved PS1 after residues ENDD329 and to a lesser extent after residues AQRD341. A second group consisting of caspase-3, -7 and -1 acted uniquely on AQRD341. Importantly, these two cleavage sites were... | SIGNOR-261756 |
Q9P2Y5 | Q6NUQ1 | 2 | binding | up-regulates activity | 0.497 | We further show that UVRAG interacts with RINT-1, and acts as an integral component of the RINT-1-containing ER tethering complex, which couples phosphoinositide metabolism to COPI-vesicle tethering. Displacement or knockdown of UVRAG profoundly disrupted COPI cargo transfer to the ER and Golgi integrity | SIGNOR-265028 |
P63096 | P31391 | 2 | binding | up-regulates activity | 0.504 | 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- signali... | SIGNOR-256680 |
Q92630 | Q00987 | 0 | ubiquitination | down-regulates quantity by destabilization | 0.57 | Under normal conditions, nuclear and not cytoplasmic DYRK2 is ubiquitinated by MDM2, resulting in its constitutive degradation.|Upon exposure to genotoxic stress, ATM phosphorylates DYRK2 at Thr-33 and Ser-369, which enables DYRK2 to escape from degradation by dissociation from MDM2 and to induce the kinase activity to... | SIGNOR-275579 |
Q9BXW4 | Q96A56 | 2 | binding | up-regulates | 0.28 | These data indicate that cell death observed after tp53inp1-lc3 interaction depends on both autophagy and caspase activity. We conclude that tp53inp1 could act as a tumor suppressor by inducing cell death by caspase-dependent autophagy. | SIGNOR-196676 |
P19544 | P49841 | 0 | phosphorylation | down-regulates quantity by destabilization | 0.284 | Glycogen synthase kinase 3β promoted phosphorylation of cugWT1 at S64, resulting in ubiquitination and degradation of the cugWT1 associated with the F-box-/- WD repeat-containing protein 8. | SIGNOR-277540 |
O60674 | P41597 | 1 | phosphorylation | up-regulates activity | 0.605 | JAK2 phosphorylates CCR2 at the Tyr139 position and promotes JAK2/STAT3 complex association to the receptor. | SIGNOR-251345 |
Q93034 | P17612 | 0 | phosphorylation | up-regulates activity | 0.322 | Elimination of the S730 but not the T325 PKA phosphorylation site of VACM-1 resulted in a complete inhibition of the VACM-1 activity, thus suggesting a direct effect of PKA on the VACM-1 receptor. | SIGNOR-250352 |
P28562 | P27361 | 2 | dephosphorylation | down-regulates activity | 0.786 | We demonstrate that ERK, JNK, and p38 are activated by distinct combinations of stimuli in T cells that simulate full or partial activation through the T cell receptor. These kinases are regulated by reversible phosphorylation on Tyr and Thr, and the dual specific phosphatases PAC1 and MKP-1 previously have been implic... | SIGNOR-248462 |
O95944 | Q8IZD2 | 2 | binding | up-regulates activity | 0.505 | We identify natural cytotoxicity receptor NKp44 (NKp44L), a novel isoform of the mixed-lineage leukemia-5 protein, as a cellular ligand for NKp44. Unlike the other MLL family members, NKp44L is excluded from the nucleus, but expressed at the cell-surface level; its subcellular localization is being associated with the ... | SIGNOR-260045 |
Q9UJ41 | Q15276 | 2 | binding | up-regulates | 0.942 | We show that rabaptin-5 increases the exchange activity of rabex-5 on rab5. | SIGNOR-109395 |
P31749 | Q15942 | 1 | phosphorylation | down-regulates | 0.415 | Akt binds and phosphorylates zyxin on serine 142, leading to its association with acinus zyxin is a substrate of caspases, but akt phosphorylation fails to protect its proteolytic degradation | SIGNOR-156122 |
O14950 | O43293 | 0 | phosphorylation | up-regulates | 0.511 | Hzipk phosphorylated the regulatory light chain of myosin ii (mrlc) at both ser19 and thr18 in vitro. Phosphorylation of mrlc is required to generate the driving force in the migration of the cells but not necessary for localization of myosin ii at the leading edge. | SIGNOR-16043 |
Q13043 | Q12778 | 1 | phosphorylation | up-regulates | 0.595 | Bonni and coworkers demonstrated that mst1 can phosphorylate foxo3 (and subsequently, foxo1) principally ser207 (ser212 in foxo1), a conserved site in the forkhead domain. This phosphorylation interdicts 14-3-3 binding, promotes foxo nuclear residence and transcriptional activity. The other major signaling modules that... | SIGNOR-191847 |
P27361 | Q13485 | 1 | phosphorylation | up-regulates | 0.419 | Our results suggest that map kinase can phosphorylate thr276 of smad4 and that phosphorylation can lead to enhanced tgf-beta-induced nuclear accumulation and, as a consequence, enhanced transcriptional activity of smad4. | SIGNOR-101664 |
P38936 | P06493 | 2 | binding | down-regulates | 0.881 | P21 and p27 are key inhibitors of both cdk1 and cdk2. | SIGNOR-128442 |
Q6ZVD8 | P17252 | 1 | dephosphorylation | down-regulates quantity | 0.253 | In addition, knockdown of PHLPP expression reduces the rate of phorbol ester-triggered dephosphorylation of the hydrophobic motif, but not turn motif, of PKC alpha | SIGNOR-237051 |
P36888 | Q13191 | 0 | ubiquitination | down-regulates activity | 0.326 | Functionally, CBL negatively regulated FMS-like tyrosine kinase 3 (FLT3) activity and interacted with human FLT3 via the autophosphorylation sites Y589 and Y599 and colocalized in vivo. | SIGNOR-260106 |
P25098 | P15311 | 1 | phosphorylation | up-regulates | 0.2 | Grk2 phosphorylates glutathione s-transferase (gst)-ezrin, but not an ezrin fusion protein lacking threonine 567 (t567), in vitro. These results suggest that t567, the regulatory phosphorylation site responsible for maintaining ezrin in its active conformation, represents the principle site of grk2-mediated phosphoryla... | SIGNOR-135622 |
Q14940 | P49407 | 0 | relocalization | down-regulates activity | 0.401 | Internalization of the Na(+)/H(+) exchanger NHE5 into recycling endosomes is enhanced by the endocytic adaptor proteins beta-arrestin1 and -2, best known for their preferential recognition of ligand-activated G protein-coupled receptors (GPCRs) | SIGNOR-275505 |
P00519 | Q92993 | 1 | phosphorylation | down-regulates activity | 0.647 | We present evidence that Tip60 is modified on tyrosine 327 by Abl kinase. We show that this causes functional changes in HAT activity and the subcellular localization of TIP60, which forms a complex with Abl kinase. The Tip60 mutation Y327F abolished tyrosine phosphorylation, reduced the inhibition of Tip60 HAT activit... | SIGNOR-276598 |
Q16236 | P00390 | 1 | transcriptional regulation | up-regulates quantity by expression | 0.405 | NFE2L2 is stabilized and translocates to the nucleus, where it dimerizes with sMAF proteins. This complex binds to AREs to mediate the transcription of genes involved in iron metabolism, GSH metabolism, and ROS detoxification.Importantly, GCLC, GCLM, GSS, and GSR are transcriptional targets of NFE2L2. Their upregulatio... | SIGNOR-279871 |
P10644 | O43164 | 0 | polyubiquitination | down-regulates quantity by destabilization | 0.379 | Praja2 controls the stability of PKA regulatory subunits. Praja2 ubiquitylates RIIα/β subunits. Subunits | SIGNOR-271855 |
Q15118 | P31751 | 2 | phosphorylation | up-regulates activity | 0.375 | Since both AKT-1, AKT-2, and SGK-1 are phosphorylated by PDK-1 and are themselves capable of phosphorylating DAF-16, their direct contact may reflect a temporary, regulatory interaction.|This demonstrates that functional PDK-1 is required to activate AKT-1, AKT-2, and SGK-1 in vivo. | SIGNOR-279248 |
P28482 | O75582 | 1 | phosphorylation | up-regulates | 0.617 | Together, our in vivo and in vitro studies indicate that the pkc/c-raf/mek/erk pathway plays a major role in the s6k1 activation in hypertrophic cardiac growth. | SIGNOR-131311 |
Q04206 | P49841 | 0 | phosphorylation | up-regulates | 0.357 | Rela is phosphorylated at: ser276 by the catalytic subunit of protein kinase a (pkac), msk1 and msk2; at ser311 by the atypical pkczeta; at ser468 by ikkbeta, ikkepsilon and glycogen-synthase kinase-3beta (gsk3beta); at ser529 by ck2; and at ser536 by ikkbeta, ikkalfa, ikkepsilon, nf-kb activating kinase (nak, also kno... | SIGNOR-151422 |
P49841 | P53805 | 1 | phosphorylation | up-regulates activity | 0.484 | Consensus phosphorylation sites for p42/44 MAPK and GSK-3 are present in the SP repeat of MCIP1 at serine 112 and serine 108, respectively |Several endogenous proteins are capable of inhibiting the catalytic activity of calcineurin. Modulatory calcineurin interacting protein 1 (MCIP1) is unique among these proteins on ... | SIGNOR-249359 |
P45983 | Q05655 | 0 | phosphorylation | up-regulates | 0.501 | By contrast, after uv stimulation, rela directly induces the expression of pkcdelta, which in turn activates jnk. | SIGNOR-151428 |
P43357 | Q13263 | 2 | binding | up-regulates activity | 0.435 | In this study, we demonstrated that the tripartite motif-containing protein 28 (TRIM28) binds directly to and promotes FBP1 for ubiquitination and degradation. MAGE-A3 and MAGE-C2, which are known to be overexpressed in HCC, can enhance TRIM28-dependent degradation of FBP1 by forming ubiquitin ligase complexes with TRI... | SIGNOR-267592 |
P35348 | P38405 | 2 | binding | up-regulates activity | 0.278 | 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- signali... | SIGNOR-256955 |
P51668 | Q9C040 | 2 | binding | up-regulates activity | 0.277 | Here, we show that TRIM RING finger protein TRIM2, highly expressed in the nervous system, is an UbcH5a-dependent ubiquitin ligase. We further demonstrate that TRIM2 binds to neurofilament light subunit (NF-L) and regulates NF-L ubiquitination. Together, our results indicate that TRIM2 is an ubiquitin ligase that binds... | SIGNOR-271775 |
P67775 | O15344 | 0 | ubiquitination | down-regulates quantity by destabilization | 0.453 | MID1, mutated in Opitz syndrome, encodes an ubiquitin ligase that targets phosphatase 2A for degradation | SIGNOR-271467 |
Q14344 | P49683 | 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- signali... | SIGNOR-257280 |
P04150 | Q13886 | 1 | transcriptional regulation | up-regulates quantity by expression | 0.321 | We show that in addition, DEX-bound GR directly promotes the expression of adipogenic TFs, including C/EBPβ, Klf5, Klf9, and C/EBPα | SIGNOR-256119 |
O94916 | P26447 | 1 | transcriptional regulation | up-regulates quantity by expression | 0.478 | As expected, the depletion of NFAT5 decreased the S100A4 and LCN2 mRNA levels (Figure 3a). In addition, chromatin immunoprecipitation (ChIP) assay using NFAT5 antibody indicated that NFAT5 was bound to the S100A4 and LCN2 promoters (Figure 3b, Supplementary Figure S3), as expected (Chen et al., 2009). | SIGNOR-274115 |
Q99956 | Q16539 | 1 | dephosphorylation | down-regulates | 0.701 | These properties define the ability of this enzyme to dephosphorylate and inactivate erk1/2 and p38a, but not jnk (c-jun n-terminal kinase) in vivo. | SIGNOR-87150 |
P12931 | Q96P31 | 1 | phosphorylation | up-regulates activity | 0.2 | Tyrosine phosphorylation of SPAP2a by c-Src and in vitro. Tyrosine-phosphorylated SPAP2 is specifically associated with SH2 domain-containing tyrosine kinases Syk and Zap70 and SH2 domain-containing tyrosine phosphatases SHP-1 and SHP-2. Site-specific mutagenesis studies revealed that tyrosyl residues 650 and 662 embed... | SIGNOR-274008 |
Q9HCU9 | P68400 | 0 | phosphorylation | down-regulates quantity by destabilization | 0.473 | We show that BRMS1 is posttranslationally regulated by TNF-induced casein kinase 2 catalytic subunit (CK2α') phosphorylation of nuclear BRMS1 on serine 30 (S30), resulting in 14-3-3ε-mediated nuclear exportation, increased BRMS1 cytosolic expression, and ubiquitin-proteasome-induced BRMS1 degradation. | SIGNOR-266407 |
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