IdA stringlengths 6 21 | IdB stringlengths 6 21 | labels float64 0 2 | mechanism stringclasses 40 values | effect stringclasses 10 values | score float64 0.1 0.99 ⌀ | sentence stringlengths 10 1.63k ⌀ | signor_id stringlengths 12 14 |
|---|---|---|---|---|---|---|---|
P26583 | P09086 | 1 | binding | up-regulates activity | 0.32 | HMG2 and Oct2 interact via their HMG domains and POU homeodomains, respectively. This interaction is not restricted to Oct2, as other members of the octamer transcription factor family like Oct1 and Oct6 also interact with HMG2. The interaction with HMG2 results in a marked increase in the sequence-specific DNA binding activity of the Oct proteins | SIGNOR-240108 |
P50750 | Q15797 | 1 | phosphorylation | down-regulates | 0.32 | Phosphorylation of the linker region of smad1, a receptor-activated smad (r-smad), at serine 206 (s206) and s214 induced by bmp and mediated by cdk8/9 is critical for binding of the e3 ubiquitin ligase smurf1. Binding of smurf1 leads to polyubiquitination of smad1 and its degradation by the proteasome;cdk8 and cyclint-cdk9 showed a preference for s206 and s214 but also phosphorylated s186 and s195 in the case of smad1;and t179, s208 and s213 in the case of smad3. | SIGNOR-161569 |
P68400 | Q04724 | 1 | phosphorylation | up-regulates | 0.32 | These results suggest that ck2 phosphorylation of serine 239 of gro/tle1 is important for its function during neuronal differentiation. | SIGNOR-129026 |
Q9NXK8 | P30838 | 1 | binding | down-regulates quantity by destabilization | 0.32 | We now show that SCFFBXL12 is an authentic E3 for the ALDH3 family of enzymes. We now show that the ubiquitin-dependent degradation of ALDH3 mediated by FBXL12 (F box and leucine-rich repeat protein 12) is essential for execution of the differentiation program of trophoblast stem cells (TSCs). FBXL12 is present only in eutherian mammals, and its expression is largely restricted to the placenta during mouse embryogenesis. FBXL12 was found to interact specifically with members of the ALDH3 family and to mediate their polyubiquitylation. Finally, coimmunoprecipitation analysis revealed that FBXL12 interacted efficiently only with members of the ALDH3 family (ALDH3A1, ALDH3A2, and ALDH3B1), showing little if any association with those of the ALDH1 family (ALDH1A1, ALDH1A2, and ALDH1A3) (Fig. 2H). Collectively, these results suggested that SCFFBXL12 is an authentic E3 specific for ALDH3 family members. | SIGNOR-272813 |
Q9Y4K3 | Q9BVN2 | 1 | polyubiquitination | down-regulates quantity by destabilization | 0.32 | We demonstrated that NESCA and NEMO interact by their N-terminal region. Beside to NEMO, we revealed that NESCA directly associates to the E3 ubiquitin ligase TRAF6, which in turn catalyzes NESCA polyubiquitination. Finally, we demonstrated that NESCA overexpression strongly inhibits TRAF6-mediated polyubiquitination of NEMO. | SIGNOR-272774 |
P53779 | O60282 | 1 | phosphorylation | down-regulates activity | 0.32 | Mass spectrometry identified a residue in the kinesin-1 motor domain that was phosphorylated by JNK3 and this modification reduced kinesin-1 binding to microtubules. JNK3 phosphorylates kinesin-1 at Ser176 | SIGNOR-262950 |
Q96PU5 | Q9Y5Y9 | 1 | ubiquitination | down-regulates quantity by destabilization | 0.32 | The control of Nav density at the cell membrane is crucial to ensuring normal neuronal excitability. Navs are subject to posttranslational modifications that may influence their cell membrane availability. Ubiquitylation is a key process that orchestrates the internalization and subsequent degradation or recycling of Navs. This is accomplished by ubiquitin protein ligases, such as NEDD4-2 (neuronal precursor cell expressed developmentally downregulated-4 type 2). | SIGNOR-253463 |
A6NLU0 | P14635 | 1 | ubiquitination | down-regulates quantity by destabilization | 0.32 | We conclude that, like many RING-finger containing proteins, RFPL4 is an E3 ubiquitin ligase. The specificity of its expression and these interactions suggest that RFPL4 targets cyclin B1 for proteasomal degradation, a key aspect of oocyte cell cycle control during meiosis and the crucial oocyte-to-embryo transition to mitosis. | SIGNOR-271476 |
P12931 | P42680 | 1 | phosphorylation | up-regulates activity | 0.32 | The proximal event following T cell-APC synapse formation is immediate activation of several signaling molecules: The Src kinase phosphorylates and activates Tec tyrosine kinases, which then activate PLC-\u03b3 that is required for IP 3 generation to sustain intracellular calcium flux. | SIGNOR-280135 |
Q00535 | P46531 | 1 | phosphorylation | up-regulates activity | 0.32 | An in vitro kinase reaction demonstrated that T2132, S2136, and S2141 were CDK5\u2010phosphorylated sites in the Notch1 peptide (Figure\u00a02B, C, and D).|In conclusion, CDK5 positively regulates Notch1 function via phosphorylation, which in turn promotes cell proliferation and migration. | SIGNOR-279401 |
P27361 | P11362 | 1 | phosphorylation | down-regulates | 0.32 | Erk-mediated phosphorylation of fibroblast growth factor receptor 1 on ser777 inhibits signaling | SIGNOR-200884 |
P62837 | Q9P253 | 1 | binding | up-regulates activity | 0.32 | VPS18 Ubiquitylates SNK in Vitro and in Vivo. The ubiquitylation of proteins by hVPS18 was selectively mediated by UbcH4. | SIGNOR-271549 |
Q16539 | O43521 | 1 | phosphorylation | down-regulates quantity by destabilization | 0.32 | Ser69 can also be phosphorylated by JNK and p38MAPK at least in vitro. Phosphorylation of BimEL on Ser69 promotes its ubiquitination. | SIGNOR-260442 |
O43303 | P0DP23 | 1 | binding | up-regulates activity | 0.32 | We report that CP110 interacts with two different Ca2+-binding proteins, calmodulin (CaM) and centrin, in vivo. our data demonstrate a functional role for CaM binding to CP110 and suggest that CP110 cooperates with CaM and centrin to regulate progression through cytokinesis. | SIGNOR-265965 |
Q9NXK8 | P43353 | 1 | binding | down-regulates quantity by destabilization | 0.32 | We now show that SCFFBXL12 is an authentic E3 for the ALDH3 family of enzymes. We now show that the ubiquitin-dependent degradation of ALDH3 mediated by FBXL12 (F box and leucine-rich repeat protein 12) is essential for execution of the differentiation program of trophoblast stem cells (TSCs). FBXL12 is present only in eutherian mammals, and its expression is largely restricted to the placenta during mouse embryogenesis. FBXL12 was found to interact specifically with members of the ALDH3 family and to mediate their polyubiquitylation. Finally, coimmunoprecipitation analysis revealed that FBXL12 interacted efficiently only with members of the ALDH3 family (ALDH3A1, ALDH3A2, and ALDH3B1), showing little if any association with those of the ALDH1 family (ALDH1A1, ALDH1A2, and ALDH1A3) (Fig. 2H). Collectively, these results suggested that SCFFBXL12 is an authentic E3 specific for ALDH3 family members. | SIGNOR-272815 |
Q05397 | O14939 | 1 | phosphorylation | up-regulates activity | 0.32 | The kinase domain of FAK interacts with PLD2-PH and induces tyrosine phosphorylation and activation of PLD2. | SIGNOR-279480 |
P49840 | P46531 | 1 | phosphorylation | down-regulates | 0.319 | Taken together, our results indicate that gsk-3alfa is a negative regulator of notch1/nicd. | SIGNOR-183969 |
P08047 | P08581 | 1 | transcriptional regulation | up-regulates quantity by expression | 0.319 | Furthermore, in transient cotransfection assays, overexpression of Sp1 and/or Sp3 stimulated HGF promoter activity independently and additively through binding to the Sp1 binding site in the HGF gene promoter region. | SIGNOR-241490 |
Q969K3 | Q9UBK2 | 1 | ubiquitination | down-regulates quantity by destabilization | 0.319 | Mechanistically, PGC1α was phosphorylated at serine (S) 636 by DNA-dependent protein kinase in response to irradiation. Phosphorylation at S636 promoted the degradation of PGC1α by facilitating its binding to the E3 ligase RNF34. | SIGNOR-277912 |
P68400 | Q96FW1 | 1 | phosphorylation | up-regulates activity | 0.319 | Casein kinase 2 (CK2)-dependent phosphorylation of OTUB1 at Ser16 played a critical role in ODN- and cathepsin K siRNA-mediated p53 stabilization. |Furthermore, although OTUB1 dramatically induced p53 deubiquitination, its mutant (S16A) and deletion mutant did not have this effec | SIGNOR-276527 |
Q15418 | Q9H6Z4 | 1 | phosphorylation | up-regulates quantity | 0.319 | RSK phosphorylates RanBP3 at Serine 58 residue in vitro and in vivo.RanBP3 phosphorylation increases its affinity towards Ran | SIGNOR-276149 |
P17252 | Q9UKF7 | 1 | phosphorylation | up-regulates activity | 0.319 | Only BIM-I caused a reduction in 14-3-3 binding (Figure 3B), suggesting that PKC could be responsible for one or both of the serine phosphorylations, pSer274 and pSer299. | SIGNOR-273801 |
Q9H4B4 | P37840 | 1 | phosphorylation | down-regulates activity | 0.319 | Polo-like kinase (plk) family (plk1, plk2, and plk3) phosphorylate alpha-syn and beta-syn specifically at ser-129 and ser-118, respectively. Polo-like kinase 2 (plk2) phosphorylates alpha-synuclein at serine 129 in central nervous system. The membrane association of pd-linked mutant alpha -synuclein, but not wild-type -synuclein, was increased by serine 129 phosphorylation. | SIGNOR-189053 |
Q9H0M0 | P04637 | 1 | ubiquitination | up-regulates activity | 0.319 | Unlike other E3 ligases, WWP1 increases p53 stability; inhibition of WWP1 expression or expression of a ligase-mutant form results in decreased p53 expression.|WWP1 associates with p53 and induces p53 ubiquitylation. | SIGNOR-278649 |
P05771 | P41180 | 1 | phosphorylation | down-regulates activity | 0.319 | Expression of a mutant CaR in which the major PKC phosphorylation site is altered by substitution of alanine for threonine (T888A) eliminated oscillatory behavior, producing [Ca(2+)](i) responses almost identical to those produced by the wild type CaR exposed to PKC inhibitors. These results support a model in which phosphorylation of the CaR at the inhibitory threonine 888 by PKC provides the negative feedback needed to cause [Ca(2+)](i) oscillations mediated by this receptor. | SIGNOR-249176 |
P17844 | P10275 | 1 | binding | up-regulates | 0.319 | P68 is a nuclear protein and interacts with ar / p68 co-occupies the active psa promoter at are regions and enhances ar transcriptional activity | SIGNOR-181456 |
P34969 | P50148 | 1 | binding | up-regulates activity | 0.319 | 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-257381 |
P31749 | Q96J02 | 1 | phosphorylation | up-regulates quantity | 0.319 | AKT1-mediated phosphorylation of ITCH at Ser257 drives its nuclear translocation | SIGNOR-272922 |
Q13428 | O60934 | 1 | relocalization | up-regulates activity | 0.319 | We further identify TCOF1 (also known as Treacle), a nucleolar factor implicated in ribosome biogenesis and mutated in Treacher Collins syndrome, as an interaction partner of NBS1, and demonstrate that NBS1 translocation and accumulation in the nucleoli is Treacle dependent. | SIGNOR-265085 |
Q9P275 | P04179 | 1 | deubiquitination | up-regulates quantity by stabilization | 0.319 | Protein stability of mitochondrial superoxide dismutase SOD2 is regulated by USP36|Finally, USP36 was shown to be a specific deubiquitinating enzyme that reduces the ubiquitination level of SOD2 and was involved in SOD2 protein stability by extending its half-life. | SIGNOR-272280 |
Q9H4L7 | Q13547 | 1 | binding | up-regulates activity | 0.319 | SMARCAD1 interacts with HDAC1 and KAP1 and is required for their binding to heterochromatin | SIGNOR-239835 |
Q03112 | P15976 | 1 | transcriptional regulation | up-regulates quantity by expression | 0.319 | We finally observed that the forced expression of Evi1 induced GATA-2 expression in a hematopoietic cell line, EML C1, along with GATA-1, Ang-1, Ang-2 and Tie2 | SIGNOR-266061 |
Q15303 | P48736 | 1 | binding | up-regulates | 0.319 | Pi3k is the sole binding partner to six tyrosines of erbb3 and one in erbb4. | SIGNOR-146888 |
Q92630 | Q00613 | 1 | phosphorylation | up-regulates activity | 0.318 | To test whether in a similar way DYRK2 phosphorylates and activates HSF1 in human cancer cells, we overexpressed DYRK2 and, by use of phosphospecific antibodies, we observed that the levels of endogenous HSF1 phosphorylated at S326 and S320 (two main phosphorylation events linked to HSF1 activation) were increased (Fig.\u00a0 xref ).|Together, these results show that DYRK2 phosphorylates HSF1 in cells and in vitro at S320 and also at S326, which is critical for HSF1 activation.Next, to test whether endogenous DYRK2 plays a role in HSF1 activation by proteotoxic stress, we used the prototypical HSF1 inducer heat shock (HS), in the absence or in the presence of harmine, observing that the inhibitor clearly impaired the phosphorylation of HSF1 upon HS (Fig S1F). | SIGNOR-278355 |
Q5SGD2 | Q99683 | 1 | dephosphorylation | down-regulates | 0.318 | Exogenous pp2cepsilon associated with exogenous ask1 in hek-293 cells under non-stressed conditions, inactivating ask1 by decreasing thr845 phosphorylation | SIGNOR-154554 |
Q9H6Z9 | P07550 | 1 | hydroxylation | up-regulates quantity by stabilization | 0.318 | We further show that the interaction of pVHL with beta(2)AR is dependent on proline hydroxylation (proline-382 and -395) and that the dioxygenase EGLN3 interacts directly with the beta(2)AR to serve as an endogenous beta(2)AR prolyl hydroxylase. Under hypoxic conditions, receptor hydroxylation and subsequent ubiquitylation decrease dramatically, thus attenuating receptor degradation and down-regulation. | SIGNOR-262007 |
O14713 | P18084 | 1 | binding | down-regulates activity | 0.318 | Integrins also bind to many PTBdomain-containing proteins (Calderwood et al., 2003) – including Dok1 and integrincytoplasmic-domain-associated protein 1 (ICAP1) – and these can compete with talin for binding to integrin and so can impair activation | SIGNOR-257660 |
P28482 | Q15366 | 1 | phosphorylation | up-regulates quantity by stabilization | 0.318 | We also identified 4 hnRNP-E2 MAPKERK1/2 phosphorylation sites and demonstrated that hnRNP-E2 is a bona fide MAPKERK1/2 substrate and that MAPKERK1/2-dependent phosphorylation of hnRNP-E2 at these amino acid residues is essential for increased hnRNP-E2 expression in BCR/ABL-expressing cells. Serine/threonine to alanine substitution abolishes hnRNP-E2 phosphorylation and markedly decreases its stability in BCR/ABL-expressing myeloid precursors. Consistent with the existence of a BCR/ABL-MAPK pathway that posttranslationally regulates hnRNP-E2 expression, sequence analysis of hnRNP-E2 revealed the presence of 4 consensus ERK phosphorylation sites (S/T-P)35,36 at amino acid residues 173, 189, 213, and 272 (Figure 2B). | SIGNOR-262912 |
P78527 | Q9H4A6 | 1 | phosphorylation | up-regulates activity | 0.318 | In response to DNA damage, DNA-PK phosphorylates GOLPH3, resulting in increased interaction with MYO18A, which applies a tensile force to the Golgi. Interference with the Golgi DNA damage response by depletion of DNA-PK, GOLPH3, or MYO18A reduces survival after DNA damage, whereas overexpression of GOLPH3, as is observed frequently in human cancers, confers resistance to killing by DNA-damaging agents | SIGNOR-253558 |
Q9H0Z9 | P38936 | 1 | post transcriptional regulation | up-regulates quantity by stabilization | 0.318 | Here, we found that RNPC1, an RNA-binding protein and a target of the p53 family, is required for maintaining the stability of the basal and stress-induced p21 transcript. | SIGNOR-275391 |
P51955 | P04637 | 1 | phosphorylation | down-regulates | 0.318 | NEK2 Phosphorylates p53 at Ser315 and Reduces Its Stability.|These results are consistent with NEK2 inhibiting p53 transcriptional activation functions. | SIGNOR-278488 |
Q96JC1 | Q13485 | 1 | relocalization | down-regulates activity | 0.318 | The data demonstrating binding of TLP to TGF-β and activin type II receptors and selective inhibition of Smad3/Smad4 complex formation by deregulated TLP suggest that TLP is involved in localizing these receptors and Smad4 to specific intracellular compartments, where it regulates formation of Smad3/Smad4 but not Smad2/Smad4 complexes. | SIGNOR-261377 |
P51812 | P18846 | 1 | phosphorylation | up-regulates activity | 0.318 | ATF1 and CREB can be phosphorylated by Rsk2 which is a protein kinase directly activated by Erk MAP kinase. These results suggest a signaling pathway in which Erk MAP kinase activates the c-fos enhancer by direct phosphorylation of p62TCF and by activation of Rsk related kinases that phosphorylate ATF1 and CREB.|ATF1 and CREB can be phosphorylated by Rsk2 which is a protein kinase directly activated by Erk MAP kinases. | SIGNOR-280117 |
O60315 | P50222 | 1 | transcriptional regulation | down-regulates quantity by repression | 0.318 | ZEB2 represses GAX transcription through multiple up- stream consensus binding sites. | SIGNOR-268951 |
P17252 | P04004 | 1 | phosphorylation | up-regulates quantity by stabilization | 0.318 | Phosphorylation of vitronectin on Ser362 by protein kinase C attenuates its cleavage by plasmin. | SIGNOR-248962 |
O15409 | Q13224 | 1 | transcriptional regulation | up-regulates quantity by expression | 0.318 | By interacting with CASK, TBR1 regulates several ASD candidate genes, such as GRIN2B, AUTS2 and RELN—all of which are recurrently mutated in ASD. In areas of the brain with overlapping expression patterns, such as in glutamatergic layer 6 neurons, the TBR1–FOXP2 interaction may result in co-ordinated regulation of common downstream targets. | SIGNOR-266834 |
Q9UNE7 | P29034 | 1 | polyubiquitination | down-regulates quantity by destabilization | 0.318 | S100 protein itself is ubiquitinated by CHIP in a Ca2+-dependent manner.Ubiquitylated S100 proteins are shown as (Ub)n-S100A2 and (Ub)n-S100P. The association of the S100 proteins with CHIP provides a Ca2+-dependent regulatory mechanism for the ubiquitination and degradation of intracellular proteins by the CHIP-proteasome pathway. | SIGNOR-272918 |
Q9P2R6 | P46531 | 1 | binding | up-regulates activity | 0.318 | In mammalian cells, RERE co‐immunoprecipitates with CBF1 and Notch intracellular domain (NICD), and is recruited to nuclear foci formed by over‐expressed NICD1. RERE is also necessary for NICD to activate the expression of Notch target genes. | SIGNOR-264486 |
P55210 | P49810 | 1 | cleavage | up-regulates activity | 0.318 | In decreasing order of activity, caspase-8, -3, -1, -6 and -7 proteolysed PS2 at the recognition site D326SYD329. | SIGNOR-261751 |
P48729 | O15534 | 1 | phosphorylation | down-regulates quantity by destabilization | 0.318 | CKI\u03b1-Dependent Phosphorylation and Degradation of PER1. | SIGNOR-279700 |
P36873 | P04637 | 1 | dephosphorylation | down-regulates activity | 0.318 | Protein serine/threonine phosphatase-1 dephosphorylates p53 at Ser-15 and Ser-37 to modulate its transcriptional and apoptotic activities|In addition, our results reveal that one of the molecular mechanisms by which PP-1 promotes cell survival is to dephosphorylate p53, and thus negatively regulate p53-dependent death pathway. | SIGNOR-248499 |
P68400 | O60341 | 1 | phosphorylation | up-regulates activity | 0.318 | We demonstrated here that phosphorylation and dephosphorylation of LSD1 at S131 and S137 was mediated by casein kinase 2 (CK2) and wild-type p53-induced phosphatase 1 (WIP1), respectively. LSD1, RNF168 and 53BP1 interacted with each other directly. CK2-mediated phosphorylation of LSD1 exhibited no impact on its interaction with 53BP1, but promoted its interaction with RNF168 and RNF168-dependent 53BP1 ubiquitination and subsequent recruitment to the DNA damage sites. | SIGNOR-276903 |
P60484 | O14641 | 1 | dephosphorylation | down-regulates activity | 0.318 | This showed that while both PTEN WT and the lipid phosphatase-inactive G129E mutant suppressed phosphorylation of DVL2 on serine 143 that accumulated upon PTEN knockdown, the C124S and Y138L mutants did not .|Finally, it is important to point out that while our studies show that PTEN can directly dephosphorylate DVL2 in vitro, it is possible that regulation of serine 143 phosphorylation of DVL2 by PTEN in cells may require additional protein factors, or post-translational modifications. | SIGNOR-277035 |
P53350 | Q16143 | 1 | phosphorylation | down-regulates activity | 0.318 | Polo-like kinase (plk) family (plk1, plk2, and plk3) phosphorylate alpha-syn and beta-syn specifically at ser-129 and ser-118, respectively. Polo-like kinase 2 (plk2) phosphorylates alpha-synuclein at serine 129 in central nervous system. The membrane association of pd-linked mutant alpha -synuclein, but not wild-type -synuclein, was increased by serine 129 phosphorylation. | SIGNOR-176079 |
Q9HCK8 | P48431 | 1 | transcriptional regulation | down-regulates quantity | 0.318 | Many of the most significantly up-regulated genes in Chd8+/− and Chd8−/− NPCs are involved in later stages of neuronal development, including Ascl1 [a central driver of neural reprogramming (29)], Dcx, Map2, Nefm, Neurod4, and Neurog1 (Fig. 2 E and F). Additionally, we found that Sox3 is derepressed in both Chd8+/− and Chd8−/− NPCs, and several other Sox TF members (Sox2, Sox7, and Sox11) became derepressed in the Chd8−/− cells | SIGNOR-268921 |
Q01973 | P12931 | 1 | phosphorylation | up-regulates | 0.318 | Ror1 binds to and phosphorylates c-src / ror1 kinase-dependent c-src activation | SIGNOR-196751 |
P49759 | Q96I25 | 1 | phosphorylation | up-regulates activity | 0.317 | In this work, we show that Cdc2-like kinase 1 (Clk1) phosphorylates SPF45 on eight serine residues. | SIGNOR-262710 |
Q9UQM7 | Q00975 | 1 | phosphorylation | down-regulates | 0.317 | Here, we report a direct modulation of ca(v)2.2 channel inactivation properties by 14-3-3, a family of signaling proteins involved in a wide range of biological processes.Wild-type gst fusion proteins containing the putative 14-3-3-binding motif (aa 2076__?2140) werein vitro phosphorylated at s2126 by either camkii or pka, as detected by thesequence- and phosphorylation-specific antibody, anti-ps2126 (middle panel). Phosphorylation of s2126 significantly increases its binding to recombinant 14-3-3? | SIGNOR-149684 |
P43115 | P12931 | 1 | binding | up-regulates activity | 0.317 | These results clearly demonstrate that EP3 contributes to the activation of Src and its related cell growth in A549 cells treated with PGE2. | SIGNOR-278885 |
P28482 | P41212 | 1 | phosphorylation | down-regulates | 0.317 | Tel became phosphorylated by erk on two serine residues, ser213 and ser257, in the internal domain between the hlh and ets domains. Tel lost its abilities to repress transcription through the phosphorylation. | SIGNOR-260086 |
P62258 | Q14957 | 1 | binding | up-regulates quantity by stabilization | 0.317 | Here, we demonstrate that PKB/Akt directly phosphorylates NR2C on serine 1096 (S1096). In addition, we identify 14-3-3epsilon as an NR2C interactor, whose binding is dependent on S1096 phosphorylation. These data are all consistent with a model in which NR1 and NR2C oligomerize, PKB phosphorylates S1096, and 14-3-3ε binds to phosphorylated NR2C thereby promoting NR2C-containing NMDA receptor surface expression in cerebellar granule cells. | SIGNOR-262622 |
P67775 | Q8WUI4 | 1 | dephosphorylation | up-regulates activity | 0.317 | Phosphorylation of conserved serine residues triggers association with 14-3-3 proteins and cytoplasmic relocalization of class IIa HDACs, which leads to the derepression of their target genes. |Here we identify PP2A as a phosphatase responsible for dephosphorylating the 14-3-3 binding sites in class IIa HDACs.|we demonstrate that PP2A constitutively dephosphorylates the class IIa member HDAC7 to control its biological functions as a regulator of T cell apoptosis and endothelial cell functions. | SIGNOR-248649 |
Q03113 | Q06187 | 1 | binding | up-regulates activity | 0.317 | Here we show that Ga12 binds directly to, and stimulates the activity of, Bruton’s tyrosine kinase (Btk) and a Ras GTPase-activating protein, Gap1m, in vitro and in vivo | SIGNOR-278082 |
P11309 | Q9UM11 | 1 | phosphorylation | down-regulates activity | 0.317 | Pim-1 phosphorylates Cdh1 and impairs binding of this protein to another APC/C complex member, CDC27. These modifications inhibit Skp2 from degradation.Pim-1 Impairs Cdh1 and CDC27 Interaction and Phosphorylates Cdh1. | SIGNOR-259820 |
P49715 | P22415 | 1 | binding | up-regulates activity | 0.317 | Our studies show that the human C/EBPa protein stimulates USF to bind to a USF consensus element within C/EBPa promoter and activates it by two- to threefold.The mechanism by which C/EBPa enhances USF binding and transactivation is currently under study. | SIGNOR-255701 |
Q15084 | O75460 | 1 | null | down-regulates activity | 0.317 | A resident ER protein disulfide isomerase, PDIA6, limits the duration of IRE1α activity by direct binding to cysteine148 in the luminal domain of the sensor, | SIGNOR-256536 |
Q9UPW0 | Q06413 | 1 | transcriptional regulation | up-regulates quantity by expression | 0.317 | Foxj3 transcriptionally activates Mef2c and regulates adult skeletal muscle fiber type identity. | SIGNOR-261606 |
O14818 | P17861 | 1 | binding | down-regulates quantity by destabilization | 0.317 | We saw preferential binding of XBP-1u to subunits _5, _6 and _7.2. We demonstrate that XBP-1u undergoes efficient degradation in vitro by 20S proteasomes in the absence of ubiquitination. | SIGNOR-239042 |
P27361 | P41212 | 1 | phosphorylation | down-regulates | 0.317 | Tel became phosphorylated by erk on two serine residues, ser213 and ser257, in the internal domain between the hlh and ets domains. Tel lost its abilities to repress transcription through the phosphorylation. | SIGNOR-123656 |
Q7Z6E9 | P67809 | 1 | ubiquitination | down-regulates quantity by destabilization | 0.317 | RBBP6 interacts with multifunctional protein YB-1 through its RING finger domain, leading to ubiquitination and proteosomal degradation of YB-1 | SIGNOR-271773 |
P05109 | Q15109 | 1 | binding | up-regulates activity | 0.317 | RAGE and TLR4 are well-characterized S100A8 and S100A9 receptors and expressed in AML cells Once secreted, S100A8 and S100A9 induce immune and inflammatory responses9 through interaction with receptors such as Toll-like receptor 4 (TLR4), receptor for advanced glycation end-product (RAGE), and CD33 | SIGNOR-261919 |
P23470 | P08581 | 1 | dephosphorylation | down-regulates activity | 0.317 | PTPRG activation by the P1-WD peptide affected the tyrosine phosphorylation of several signaling molecules. Data analysis identified 31 molecules whose phosphorylation was modified in a statistically significant manner (Table I). inhibition of ABL1, BMX, BTK, DAB1, ITGB1, JAK2, KDR, KIT, LIMK1, MET, PDGFRB, SHC1, and VCL correlates with tyrosine dephosphorylation. In contrast, SRC inhibition correlates with hyperphosphorylation of the inhibitory Tyr530 residue and with dephosphorylation of the activatory Tyr419. Moreover, CDK2 and CTTN inhibition correlates with a hyperphosphorylation of the inhibitory Tyr15 and Tyr470, respectively. In contrast, a subgroup of 13 proteins, including BLNK, DOK2, ERBB2, GRIN2B, INSR, PDGFRA, PRKCD, PXN, STAT1, STAT2, STAT3, STAT5A, and ZAP70, appears to be activated by PTPRG activity. | SIGNOR-254712 |
P61328 | Q9UQD0 | 1 | binding | down-regulates activity | 0.317 | Sodium channel fast inactivation is modulated by alpha subunit interaction with a family of cytoplasmic proteins termed fibroblast growth factor homologous factors (FHFs). In this paper, we report that all A-type FHFs exert rapid onset long-term inactivation on Nav1.6 and other sodium channels. | SIGNOR-253412 |
Q8WV44 | P05771 | 1 | polyubiquitination | down-regulates quantity by destabilization | 0.317 | RINCK induces the ubiquitination of PKC both in vitro and in cells. Overexpression of RINCK reduces the levels of PKC in cells, whereas genetic knockdown of endogenous RINCK increases the levels of PKC. The RINCK-mediated ubiquitination is likely to be polyubiquitination, because the ubiquitinated PKCβII was detected as a high molecular weight smear. | SIGNOR-271667 |
Q02078 | P35580 | 1 | transcriptional regulation | up-regulates quantity by expression | 0.317 | Myocyte enhancer factor-2 and serum response factor binding elements regulate fast Myosin heavy chain transcription in vivo. We show that the upstream promoter region of the gene most abundantly expressed in mouse skeletal muscles, IIb MyHC, retains binding activity and transcriptional activation for three positive transcription factors, the serum response factor, Oct-1, and myocyte enhancer factor-2, whereas the other two genes (IIa and IId/x) have nucleotide substitutions in these sites that reduce binding and transcriptional activation | SIGNOR-238763 |
Q96PU5 | Q99250 | 1 | ubiquitination | down-regulates quantity by destabilization | 0.317 | The control of Nav density at the cell membrane is crucial to ensuring normal neuronal excitability. Navs are subject to posttranslational modifications that may influence their cell membrane availability. Ubiquitylation is a key process that orchestrates the internalization and subsequent degradation or recycling of Navs. This is accomplished by ubiquitin protein ligases, such as NEDD4-2 (neuronal precursor cell expressed developmentally downregulated-4 type 2). | SIGNOR-253459 |
Q15059 | Q09472 | 1 | binding | up-regulates activity | 0.317 | Brd3 interacts with both IRF3 and p300, increases p300-mediated acetylation of IRF3, and enhances the association of IRF3 with p300 upon virus infection.|Brd3 enhances p300-mediated acetylation of IRF3 | SIGNOR-262044 |
P07947 | Q9GZV5 | 1 | phosphorylation | up-regulates activity | 0.317 | Yes directly phosphorylates YAP and TAZ, resulting in their increased nuclear localization and transcriptional activity.Analysis by mass spectrometry identified Tyr391 and Tyr407 as the two phosphorylation sites of YAP, whereas Tyr305 was the sole phosphorylated residue of TAZ (Fig. 5F and fig. S4, A to C). | SIGNOR-277654 |
P27361 | P24928 | 1 | phosphorylation | down-regulates | 0.316 | Erk1/2 are major ser-5 kinases after h2o2 treatment. These results suggest that subsequent to h2o2 treatment, the ser-5-phosphorylated form, but not the ser-2-phosphorylated form or the unphosphorylated form, is targeted for rapid proteasomal degradation through its ubiquitination. | SIGNOR-120176 |
O14965 | P23528 | 1 | phosphorylation | down-regulates activity | 0.316 | However, this study identified that CFL-1 also acts as a direct substrate of Aur-A, which phosphorylates CFL-1 at multiple sites, including S3, S8, and T25, resulting in its inactivation.|In early cell mitotic phases, LIMK1 and Aur-A phosphorylate and inactivate CFL-1, while at the later stages, SSH-1 inactivates LIMK1 and dephosphorylates and activates CFL-1 [33] . | SIGNOR-279798 |
O15530 | P24723 | 1 | phosphorylation | up-regulates activity | 0.316 | Protein kinase C(eta) is phosphorylated by PDK1 in vitro, leading to kinase activation as similarly reported for protein kinase C(epsilon) activation by PDK1. | SIGNOR-280062 |
P53350 | Q15208 | 1 | phosphorylation | down-regulates activity | 0.316 | Here, we identified a conserved signaling axis in which NDR1 kinase activity is regulated by PLK1 in mitosis. PLK1 phosphorylates NDR1 at three putative threonine residues (T7, T183 and T407) at mitotic entry, which elicits PLK1-dependent suppression of NDR1 activity and ensures correct spindle orientation in mitosis. | SIGNOR-276914 |
P45983 | P16949 | 1 | phosphorylation | down-regulates | 0.316 | Involved in the regulation of the microtubule (mt) filament system by destabilizing microtubules. Prevents assembly and promotes disassembly of microtubules. Here we show that in response to hyperosmotic stress, jnk phosphorylates a key cytoplasmic microtubule regulatory protein, stathmin (stmn), on conserved ser-25 and ser-38 residues. In in vitro biochemical studies, we identified stmn ser-38 as the critical residue required for efficient phosphorylation by jnk and identified a novel kinase interaction domain in stmn required for recognition by jnk. We revealed that jnk was required for microtubule stabilization in response to hyperosmotic stress. | SIGNOR-166694 |
O43293 | P38936 | 1 | phosphorylation | up-regulates quantity by stabilization | 0.316 | ZIP kinase phosphorylates p21(WAF1) at Thr145 and alanine-substituted mutations in the p21(WAF1) phosphorylation site alter its ability to be phosphorylated by ZIP kinase. | Transfected ZIPK can promote the phosphorylation of p21(WAF1) at Thr145 in vivo and can increase the half-life of p21(WAF1) | SIGNOR-251085 |
P46934 | Q2KJY2 | 1 | ubiquitination | down-regulates quantity by destabilization | 0.316 | Nedd4 polyubiquitinates Kif26b and thus targets it for degradation via the ubiquitin-proteasome pathway. | SIGNOR-278767 |
Q16539 | O75928 | 1 | phosphorylation | up-regulates activity | 0.316 | The switch between the coactivating and inhibitory actions of PIASxα is controlled, at least in part, through PIASxα phosphorylation. PIASxα is itself phosphorylated by p38 in vitro and in vivo in response to the activation of stress signaling pathways (Figure 2, Figure 3, Figure 4). We identify Ser113 and Ser 116 as two residues that are phosphorylated by p38 and have important functional roles | SIGNOR-262949 |
P30530 | P04626 | 1 | phosphorylation | down-regulates activity | 0.316 | Blockade of Axl function abrogated phosphorylation of ERBB2 (Her-2 and neu) at the Tyr877 residue, indicative of receptor crosstalk.|We have demonstrated that either pharmacological or genetic inhibition of Axl function abrogates phosphorylation of ERBB2 at the critical Tyr877 residue and sensitizes OE33 cells to lapatinib in vitro. | SIGNOR-280193 |
O95644 | P35354 | 1 | transcriptional regulation | up-regulates quantity by expression | 0.316 | NFAT induces the transcription of the COX2 (cyclo-oxygenase-2) gene incancer cells thereby enhancing invasive migration | SIGNOR-264026 |
O14965 | Q96EZ8 | 1 | phosphorylation | up-regulates activity | 0.316 | We conclude that Aurora-A phosphorylates MCRS1 on Ser35/36 specifically during mitosis. | SIGNOR-278232 |
Q9UKG1 | Q15831 | 1 | binding | up-regulates | 0.316 | In this study, we identified lkb1 as a new binding partner of appl1 and showed that the bar domain of appl1 is involved in this interaction.Here we show that in muscle cells adiponectin and metformin induce ampk activation by promoting appl1-dependent lkb1 cytosolic translocation. Appl1 mediates adiponectin signaling by directly interacting with adiponectin receptors and enhances lkb1 cytosolic localization by anchoring this kinase in the cytosol. | SIGNOR-186065 |
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 Thr-76 | SIGNOR-100177 |
Q16539 | P10636 | 1 | phosphorylation | up-regulates | 0.316 | A large number of cytosolic proteins can be phosphorylated by p38 mapks, including phospholipase a2, the microtubule-associated protein tau, nhe-1, cyclin d1, cdk inhibitors, bcl2 family proteins, growth factor receptors or keratins. | SIGNOR-166611 |
P49841 | O15033 | 1 | phosphorylation | down-regulates quantity by destabilization | 0.316 | These experiments suggested that GSK3beta phosphorylation of FIEL1 is required for PIAS4 targeting, and FIEL1 residues P779 and phosphorylated T783 are both required for PIAS4 interaction |FIEL1 T783A mutant overexpression completely failed to decrease PIAS4 protein level. | SIGNOR-275528 |
Q04206 | P56524 | 1 | binding | up-regulates | 0.316 | P65 and histone deacetylases 4 cooperate to inhibit the ability of mef2 factors to induce the klf2 promoter | SIGNOR-138368 |
Q9UQB3 | P33151 | 1 | binding | up-regulates quantity by stabilization | 0.316 | To clarify the role of p120 in mammalian cells, we have knocked down p120 with siRNA in cells expressing epithelial (E-), placental (P-), neuronal (N-), and vascular endothelial (VE-) cadherins. We report that each of these cadherins, as well as α- and β-catenins, were rapidly degraded in the absence of p120, resulting in loss of cell–cell adhesion. The effect was clearly dose dependent, indicating that p120 expression levels may directly determine cadherin levels. Degradation of p120-uncoupled cadherin occurred after its arrival at the surface, indicating that p120 regulates cadherin turnover at the level of internalization or recycling. p120 homologues ARVCF and δ-catenin could substitute for p120, so at least one family member is likely required to maintain adhesion. Thus, cadherin complexes are rapidly turned over and degraded in mammalian cells in the absence of direct interaction with p120 or a p120 family member. | SIGNOR-252132 |
Q14164 | P05412 | 1 | phosphorylation | up-regulates activity | 0.316 | Indeed, using an in vitro kinase assay, we demonstrated that both JNK and IKKepsilon phosphorylated c-Jun (XREF_FIG and XREF_SUPPLEMENTARY). | SIGNOR-279621 |
P53350 | Q12778 | 1 | phosphorylation | down-regulates activity | 0.316 | In conclusion, we provide evidence that PLK1-dependent phosphorylation of FOXO1 induces its nuclear exclusion and negatively regulates FOXO1 transcriptional activity in PCa.|We previously demonstrated that PLK1 inhibits the transcriptional activity of FOXO1 by promoting its nuclear exclusion in U2OS cells . | SIGNOR-278269 |
Q96EP1 | Q12824 | 1 | polyubiquitination | down-regulates quantity by destabilization | 0.316 | Here we report that CHFR interacts with BRG1, SNF5, and BAF60a of the SWI/SNF-like BAF complex and ubiquitinates them to target for degradation through a proteasome-mediated pathway, and that SRG3/mBAF155 stabilizes these components by blocking their interaction with CHFR. These results suggest that CHFR enhances the degradation of the components of the SWI/SNF-like BAF complex by inducing their poly-ubiquitination. | SIGNOR-271458 |
P06493 | Q9NTG7 | 1 | phosphorylation | up-regulates activity | 0.315 | Both SIRT3 T150 and S159 phosphorylated by CDK1 indicates that CDK1-SIRT3 pathway may play a role in the overall mitochondrial protein acetylation involved in mitochondrial homeostasis and apoptosis. | SIGNOR-279395 |
Q5VU43 | P10644 | 1 | binding | up-regulates | 0.315 | Mmgl acts as a dual-specific akap by anchoring pka regulatory isoforms r1a and r2a. | SIGNOR-173769 |
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