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 |
|---|---|---|---|---|---|---|---|
Q9C0F0 | Q13133 | 1 | binding | down-regulates activity | 0.2 | We determined that ASXL3 depletion augments the ligand-induced transcriptional activities of LXRα and TRβ, which were repressed by ASXL3 overexpression. The ligand-dependent interactions of ASXL3 with LXRα and TRβ were demonstrated by the GST pull-down and immunoprecipitation analyses. We confirmed that ASXL3 suppresses the expression of LXRα target genes through its recruitment to the LXR-response elements. | SIGNOR-266765 |
Q8TAT6 | Q92890 | 1 | binding | up-regulates activity | 0.2 | These findings ascribe specific functions to each of the components of the VCP-UFD1L-NPL4 complex in Vpu-mediated CD4 degradation: VCP energizes the process through ATP binding and hydrolysis, UFD1L binds ubiquitinated CD4 through recognition of K48 Ub chains, and NPL4 stabilizes UFD1L. VCP is thus likely to provide the energy required for extraction of CD4 from membranes. | SIGNOR-252422 |
Q86Y13 | Q9BTM1 | 1 | 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 TLR activation. H2A monoubiquitination acts to prevent FACT recruitment at the transcriptional promoter region, blocking RNA polymerase II release at the early stage of elongation. | SIGNOR-271763 |
Q14689 | P42684 | 1 | binding | up-regulates activity | 0.2 | Here, using cultured hippocampal neurons pooled from both sexes of mice, we provide evidence that binding to cortactin tethers Abl2 in spines, where Abl2 and cortactin maintain the small pool of stable actin required for dendritic spine stability. | SIGNOR-266593 |
O60260 | Q96M98 | 1 | polyubiquitination | down-regulates quantity by destabilization | 0.2 | In this study, we found that CHIP promotes Parkin-mediated Pael-R ubiquitination and subsequent degradation. In vitro ubiquitination assays suggested that only a combination of both Parkin and its cofactor CHIP function as a ubiquitin ligase, which is able to sufficiently ubiquitinate Pael-R in vivo (Figure 6). | SIGNOR-272889 |
P51452 | P06748 | 1 | dephosphorylation | down-regulates activity | 0.2 | In the absence of DUSP3, these three residues remain phosphorylated and favor the dissociation equilibrium of NPM homo-oligomerization and/or its association with ARF, therefore promoting an early nuc|Therefore, here we focused on the molecular mechanisms used by DUSP3-NPM interaction to affect the abovementioned cellular responses and found out that DUSP3 dephosphorylates three tyrosine residues (Y29, Y67, and Y271) of NPM. | SIGNOR-277005 |
O95271 | 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 proteins. Using proteomics approaches, we have identified BLZF1 and CASC3 as further substrates targeted by tankyrase and RNF146 for degradation. | SIGNOR-263383 |
P06493 | Q9NQR1 | 1 | phosphorylation | up-regulates quantity by stabilization | 0.2 | We found that PR-Set7 is phosphorylated at Ser 29 (S29) specifically by the cyclin-dependent kinase 1 (cdk1)/cyclinB complex, primarily from prophase through early anaphase, subsequent to global accumulation of H4K20me1. While S29 phosphorylation did not affect PR-Set7 methyltransferase activity, this event resulted in the removal of PR-Set7 from mitotic chromosomes. S29 phosphorylation also functions to stabilize PR-Set7 by directly inhibiting its interaction with the anaphase-promoting complex (APC), an E3 ubiquitin ligase. | SIGNOR-259832 |
O95835 | Q14872 | 1 | phosphorylation | down-regulates activity | 0.2 | The Hippo pathway kinases LATS1 and LATS2 attenuate cellular responses to heavy metals through phosphorylating MTF1|the Hippo pathway kinase LATS phosphorylates and inhibits MTF1|LATS phosphorylates MTF1 at S152 and disrupts its association with the promoters of heavy metal response genes, resulting in the loss of heavy metal response gene expression | SIGNOR-275473 |
Q9HC97 | P63096 | 1 | binding | up-regulates activity | 0.2 | Here we systematically quantified ligand-induced interactions between 148 GPCRs and all 11 unique G alpha subunit C-termini. For each receptor, we probed chimeric G alpha subunit activation via a transforming growth factor-alpha (TGF alpha) shedding response in HEK293 cells lacking endogenous Gq/11- and G12/13- signaling. | We defined positive coupling if any member of the subfamily scored LogRAi ≥ -1 and negative coupling if all of the members scored LogRAi < -1 (Figure 3A-B). ROC analysis gives AUC = 0.78 (Figure S4A) when considering high-confidence known coupling data and suggested a threshold of LogRAi ≥ -1.0 for defining true couplings. | The score associated to this interaction has a LogRAi ≥ -1.0. | SIGNOR-256717 |
Q05655 | O00165 | 1 | phosphorylation | down-regulates quantity by destabilization | 0.2 | FBXO25 encodes an orphan F-box protein that determines the substrate specificity of the SCF (SKP1-CUL1-F-box)(FBXO25) ubiquitin ligase complex. An unbiased screen uncovered the prosurvival protein HCLS1-associated protein X-1 (HAX-1) as the bona fide substrate of FBXO25 that is targeted after apoptotic stresses. Protein kinase Cdelta (PRKCD) initiates this process by phosphorylating FBXO25 and HAX-1, thereby spatially directing nuclear FBXO25 to mitochondrial HAX-1.|Accordingly, PRKCD-induced phosphorylation of Hax-1 at Ser210 and Fbxo25 at Ser178 was associated with decreased expression of Hax-1 in control cells, | SIGNOR-275562 |
Q96KG9 | Q9BV73 | 1 | relocalization | down-regulates activity | 0.2 | Moreover, TEIF closely co-localized with C-NAP1 at the proximal ends of centrioles, and centriolar loading of TEIF stimulated by EGF/Akt could displace C-NAP1, resulting in centrosome splitting. | SIGNOR-265497 |
Q9H3R0 | P68431 | 1 | demethylation | down-regulates activity | 0.2 | As one member of the Jumonji-C histone demethylase family, JMJD2C has the ability to demethylate tri- or di-methylated histone 3 and 2 in either K9 (lysine residue 9) or K36 (lysine residue 36) sites by an oxidative reaction, thereby affecting heterochromatin formation, genomic imprinting, X-chromosome inactivation, and transcriptional regulation of genes.JMJD2C has been proved to be a demethylase for H3K9 methylation, in the manner of catalyzing the demethylation of H3K9me3/me2 (the known repressive markers of gene regulation), a histone mark found in heterochromatin associated with euchromatic transcriptional silencing and heterochromatin formation | SIGNOR-263864 |
O76050 | O76083 | 1 | polyubiquitination | down-regulates quantity by destabilization | 0.2 | Neuralized family member NEURL1 is a ubiquitin ligase for the cGMP-specific phosphodiesterase 9A. We also demonstrate that NEURL1 can promote polyubiquitination of PDE9A that leads to its proteasome-mediated degradation mainly via lysine residue K27 of ubiquitin. | SIGNOR-272305 |
Q9Y5H9 | Q9Y5G9 | 1 | 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-265675 |
Q9ULA0 | Q13107 | 1 | cleavage | down-regulates quantity by destabilization | 0.2 | A further analysis showed that the hydrolysis pathway contributes to DNPEP-mediated degradation of USP4 (Supporting Information Figs. S3A–S3F). The interaction between USP4 and DNPEP was confirmed by coIP assays | SIGNOR-275652 |
P23470 | P18206 | 1 | dephosphorylation | down-regulates activity | 0.2 | 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-254731 |
Q12857 | P54764 | 1 | transcriptional regulation | up-regulates quantity | 0.2 | For example, within the NFI targetome, we identified 6 collagen genes, 13 genes encoding potassium channel or glutamate receptor subunits and a range of factors related to axon guidance (e.g. Slit1, Robo1, Epha4, Epha5, Epha8) | SIGNOR-268894 |
P10275 | P10275 | 2 | binding | up-regulates activity | 0.2 | The unliganded AR resides predominately in the cytoplasm as a heteromeric complex with hsp90 and other chaperone proteins. These chaperone proteins maintain AR in a form that is receptive to ligand binding. Regulation of gene expression by androgen-activated AR occurs through receptor nuclear translocation, dimerization, and binding to androgen response elements (AREs) in the DNA of target genes. | SIGNOR-251537 |
P04626 | Q8NEM2 | 1 | phosphorylation | up-regulates activity | 0.2 | Blocking HER2 activation using trastuzumab effectively abolished EGF-induced nuclear localization of SHCBP1 in gastric cancer cells [7].|In addition, nuclear translocation of SHCBP1 is a downstream consequence of HER2 activation, which is dependent on phosphorylation of SHCBP1 at the Ser273 site. | SIGNOR-280009 |
Q13185 | P84243 | 1 | binding | up-regulates activity | 0.2 | A core characteristic of heterochromatin is its association with heterochromatin protein 1 (HP1) proteins, a highly conserved family of chromosomal proteins that bind to di- and trimethylated H3K9 via a conserved N-terminal domain called the chromodomain (CD) HP1 proteins are a highly conserved family of eukaryotic proteins that bind to methylated histone H3 lysine 9 (H3K9) and are required for heterochromatic gene silencing. | SIGNOR-264494 |
P22694 | Q6PIY7 | 1 | phosphorylation | down-regulates activity | 0.2 | We found that Gld2 activity is regulated by site-specific phosphorylation in its disordered N-terminal domain. We identified two phosphorylation sites (S62, S110) where phosphomimetic substitutions increased Gld2 activity and one site (S116) that markedly reduced activity. Using mass spectrometry, we confirmed that HEK 293 cells readily phosphorylate the N-terminus of Gld2. We identified protein kinase A (PKA) and protein kinase B (Akt1) as the kinases that site-specifically phosphorylate Gld2 at S116, abolishing Gld2-mediated nucleotide addition. | SIGNOR-259403 |
P49840 | Q9Y6Q9 | 1 | phosphorylation | down-regulates quantity by destabilization | 0.2 | GSK3 Phosphorylates SRC-3 on S505.In this report, we identified GSK3 as a kinase that phosphorylates SRC-3 on S505 and demonstrated that this phosphorylation modulates SRC-3 transcriptional function and turnover. | SIGNOR-276067 |
P16144 | O00329 | 1 | 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 |
P20309 | P08754 | 1 | binding | up-regulates activity | 0.2 | Here we systematically quantified ligand-induced interactions between 148 GPCRs and all 11 unique G alpha subunit C-termini. For each receptor, we probed chimeric G alpha subunit activation via a transforming growth factor-alpha (TGF alpha) shedding response in HEK293 cells lacking endogenous Gq/11- and G12/13- signaling. | We defined positive coupling if any member of the subfamily scored LogRAi ≥ -1 and negative coupling if all of the members scored LogRAi < -1 (Figure 3A-B). ROC analysis gives AUC = 0.78 (Figure S4A) when considering high-confidence known coupling data and suggested a threshold of LogRAi ≥ -1.0 for defining true couplings. | The score associated to this interaction has a LogRAi ≥ -1.0. | SIGNOR-256882 |
P12931 | Q15691 | 1 | phosphorylation | down-regulates activity | 0.2 | These data suggest that Src phosphorylates endogenous EB1 at Y247. | SIGNOR-278215 |
P06493 | Q8TF76 | 1 | phosphorylation | up-regulates activity | 0.2 | Phosphorylation by Cyclin B-Cdk1 allows Haspin to bind Plk1-PBD. Phosphorylation of Haspin at T128 and Plk1 target sites is required for full H3T3ph generation and normal Aurora B localization in mitosis. | SIGNOR-275419 |
O14929 | P62805 | 1 | acetylation | down-regulates activity | 0.2 | Histone acetyltransferase 1 is the founding member of the histone acetyltransferase superfamily and catalyzes lysine acetylation of newly synthesized histone H4|Lys12 for direct attack of the acetyl group of the cofactor.| It is postulated that histone acetylation, through charge neutralization of the cationic histone tails, weakens nucleosomal electrostatic interactions with anionic DNA, thus destabilizing internucleosomal contacts and nucleosomal structure and facilitating access to the promoter region for RNA polymerase and transcription factors. | SIGNOR-264790 |
Q8NFZ3 | Q9P2S2 | 1 | binding | up-regulates activity | 0.2 | Pre- and postsynaptic plasma membranes are always precisely aligned, and are separated by a synaptic cleft of ~20 nm. The cleft contains an undefined proteinaceous material in the middle, and is presumably bridged by synaptic cell-adhesion molecules such as Nrxns and Nlgns that align the pre- and postsynaptic elements and mediate trans-synaptic signaling.|Nlgns bind to both alpha- and beta-Nrxns with nanomolar affinities; binding involves the sixth LNS-domain of alpha-Nrxns which corresponds to the only LNS-domain of beta-Nrxns52. The binding affinities differ characteristically between various pairs of Nlgns and Nrxns, and are controlled by alternative splicing of both Nrxns and Nlgns (Figure 1c) | SIGNOR-264153 |
P49841 | P15260 | 1 | phosphorylation | up-regulates quantity by stabilization | 0.2 | Our data suggest that glycogen synthase kinase 3 beta (GSK3beta) phosphorylates IFNGR1 thereby enhancing receptor protein stability by limiting ubiquitin proteasomal degradation. | SIGNOR-279720 |
P27708 | P27708 | 2 | phosphorylation | up-regulates activity | 0.2 | Autophosphorylation resulted in a 2-fold increase in CPSase activity, an increased sensitivity to the feedback inhibitor UTP, and decreased allosteric activation by 5-phosphoribosyl-1-pyrophosphate | SIGNOR-250610 |
P06493 | O60610 | 1 | phosphorylation | down-regulates activity | 0.2 | In this study, we found that Cdk1 phosphorylated DIAPH1, which inhibited the interaction between DIAPH1 and profilin1 (PFN1) during metaphase.|Thus, the results suggest that the level of cortical F-actin has to be finely maintained by Cdk1 mediated positive and negative regulation of DIAPH1. | SIGNOR-279598 |
Q99698 | P51148 | 1 | binding | down-regulates activity | 0.2 | Mauve interacts with Rab5, Msps, and gamma-tubulin|Mauve/LYST opposes Rab5, which promotes vesicle fusion affecting PCM recruitment | SIGNOR-266003 |
Q9Y5I2 | Q9UN71 | 1 | 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-265701 |
P17612 | P07196 | 1 | phosphorylation | down-regulates activity | 0.2 | Phosphorylation of neurofilament-L protein (NF-L) by the catalytic subunit of cAMP-dependent protein kinase (A-kinase) inhibits the reassembly of NF-L and disassembles filamentous NF-L. | SIGNOR-252401 |
O94901 | Q3KP22 | 1 | binding | up-regulates activity | 0.2 | 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. | It will be of great interest to test this hypothesis to fully understand the mechanisms of stable telomere–NE connection and telomere movement along the NE driven by the LINC complex. | SIGNOR-263300 |
Q16236 | O00625 | 2 | transcriptional regulation | up-regulates quantity by expression | 0.2 | The activation of NFE2L2 is pivotal in protecting cells from ferroptotic death. To achieve this protective function, NFE2L2 regulates a broad spectrum of genes involved in multiple cellular pathways, including those that modulate ROS, detoxify harmful agents, and repair damaged proteins. In human pancreatic cancer cell lines, the expression of PIR is upregulated by NFE2L2 in response to ferroptosis-inducing agents (erastin or RSL3) | SIGNOR-279850 |
P17612 | Q9UL62 | 1 | phosphorylation | down-regulates quantity | 0.2 | Together, these results suggest that TRPC5 is directly phosphorylated by G(s)/cAMP/PKA at positions S794 and S796. These inhibitory effects were blocked by the protein kinase A (PKA) inhibitors, KT-5720 and H-89, as well as by two point mutations at consensus PKA phosphorylation sites on TRPC5 (S794A and S796A). | SIGNOR-277823 |
Q8IYW5 | P16403 | 1 | polyubiquitination | down-regulates | 0.2 | ITCH biochemically antagonized RNF168 and RNF8 in polyubiquitination of histone H1.2 ITCH interacts with and ubiquitinates linker histone H1.2 at K46. ITCH biochemically competes with RNF168 and RNF8 to polyubiquitinate histone H1.2. Both RNF168 and RNF8 elicited higher Ubn levels of K46R-H1.2 compared to WT-H1.2, suggesting that Ubn of H1.2 by both E3 ligases occurs at a site apart from K46. | SIGNOR-272927 |
Q14493 | P23527 | 1 | translation regulation | up-regulates quantity by expression | 0.2 | Synthesis of mature histone mRNA requires only a single processing reaction: an endonucleolytic cleavage between a conserved stem-loop and a purine-rich downstream element to form the 3' end. The stem-loop binding protein (SLBP) is required for processing, and following processing, histone mRNA is transported to the cytoplasm, where SLBP participates in translation of the histone mRNA|We used radiolabeled probes generated by PCR targeting the open reading frame (ORF) to detect histones H2A, H2B, H3, H4, and H1 and used 7SK snRNA as a loading control (Fig. 2A). The abundance of histone H2A, H2B, H3, and H4 mRNAs is reduced to 37% to 70% of control levels in the SLBP knockdown cells when compared to the C2 control. | SIGNOR-265379 |
Q00535 | Q9Y696 | 1 | phosphorylation | up-regulates quantity by stabilization | 0.2 | These results confirm that CDK5 phosphorylates CLIC4 at serine 108.|We found that activated CDK5 phosphorylated serine 108 in CLIC4, increasing CLIC4 protein stability, and accumulation. | SIGNOR-279451 |
P07948 | P07948 | 2 | phosphorylation | up-regulates activity | 0.2 | Lyn is a member of the Src family of protein-tyrosine kinases that can readily undergo autophosphorylation in vitro. The site of autophosphorylation is Tyr397. Autophosphorylation results in a 17-fold increase in protein-tyrosine kinase activity. | SIGNOR-251402 |
Q9BYB0 | P42261 | 1 | binding | up-regulates quantity | 0.2 | SHANK proteins are ‘master’ scaffolding proteins that tether and organize intermediate scaffolding proteins. They are located at excitatory synapses, where they are crucial for proper synaptic development and function. SAPAP proteins subsequently bind to the PDZ domain of members of the SHANK protein family. SHANK proteins then bind to the actin cytoskeleton and to Homer protein, which in turn interacts with mGluRs. Through these extended links, PSD95, SAPAP, SHANK and Homer proteins form a quaternary complex that brings together mGluR and NMDAR complexes in the PSD (FIG. 3). | SIGNOR-264601 |
Q92993 | P35790 | 1 | acetylation | up-regulates activity | 0.2 | Glucose deprivation induces the binding of choline kinase α2 (CHKα2) to lipid droplets, followed by a continuous PTMs to promote lipolysis of lipid droplets, which are in turn mediated by AMPK-dependent CHKα2 Serine 279 phosphorylation and KAT5-dependent CHKα2 Lysine 247 acetylation. | SIGNOR-267648 |
Q02447 | Q9UKX5 | 1 | null | up-regulates quantity by expression | 0.2 | We speculate that the "mesenchymal signature" of alpha11 integrin gene expression is controlled by the activity of Sp1/Sp3, fibroblast-specific combinations of Ets family members and yet unidentified enhancer-binding transcription factors. | SIGNOR-253351 |
Q9P2R6 | Q07812 | 1 | relocalization | up-regulates activity | 0.2 | We detected RERE protein mainly in the nucleus, where it colocalizes with the promyelocytic leukemia protein in promyelocytic leukemia oncogenic domains (PODs). Overexpression of RERE recruits a fraction of the proapoptotic protein BAX to PODS: This observation correlates with RERE-induced apoptosis, which occurs in a caspase-dependent manner. | SIGNOR-264485 |
Q99704 | P18564 | 1 | binding | down-regulates activity | 0.2 | 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-257693 |
P17612 | P42858 | 1 | phosphorylation | down-regulates quantity by destabilization | 0.2 | Moreover, phosphorylation of C-HEAT Ser2550 by cAMP-dependent protein kinase (PKA), the top hit in kinase activity screens, was found to hasten huntingtin degradation, such that levels of the catalytic subunit (PRKACA) were inversely related to huntingtin levels. | SIGNOR-277625 |
Q9Y5I2 | Q9Y5H4 | 1 | 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-265708 |
O60285 | Q96QC0 | 1 | phosphorylation | up-regulates activity | 0.2 | Here, we show that NUAK1 is a predominantly nuclear protein that associates with a network of nuclear protein phosphatase 1 (PP1) interactors and that PNUTS, a nuclear regulatory subunit of PP1, is phosphorylated by NUAK1.|Inhibition of NUAK1 abolishes chromatin association of PNUTS, reduces spliceosome activity, and suppresses nascent RNA synthesis. | SIGNOR-280051 |
P00519 | Q8N2M8 | 1 | phosphorylation | up-regulates activity | 0.2 | In biochemical assays and in Xenopus growth cones we find that Abl kinase activity enhances the association or co-localization of CLASP2 and F-actin, consistent with previous reports of CLASP binding to actin [Tsvetkov et al., ].|In vitro, Abl phosphorylates CLASP with a Km of 1.89 \u00b5M, indicating that CLASP is a bona fide substrate. | SIGNOR-280166 |
P46736 | P0C0S8 | 1 | deubiquitination | down-regulates | 0.2 | Brcc36 regulates the abundance of lys(63)-linked ubiquitin chains at chromatin and that one of its substrates is diubiquitinated histone h2a | SIGNOR-167142 |
P62136 | P42575 | 1 | dephosphorylation | up-regulates activity | 0.2 | nutrient-replete oocytes inhibit C2 via S135 phosphorylation catalyzed by calcium/calmodulin-dependent protein kinase II. We now show that C2 phosphorylated at S135 binds 14-3-3zeta, thus preventing C2 dephosphorylation. Moreover, we determined that S135 dephosphorylation is catalyzed by protein phosphatase-1 (PP1), which directly binds C2. | SIGNOR-248564 |
P06400 | P39687 | 1 | binding | down-regulates activity | 0.2 | We further demonstrate that pp32-Rb interaction inhibits the apoptotic activity of pp32 and stimulates proliferation. | SIGNOR-259083 |
Q2TAL8 | P41252 | 1 | transcriptional regulation | up-regulates quantity by expression | 0.2 | QRICH1 promotes the expression of translation-related genes. our combined ChIP-seq and RNA-seq analyses identified that QRICH1 and ATF4 were enriched at the promoters of these specific tRNA synthetases, and that ER stress positively regulated their transcription (Fig. 4I). Together, these findings suggest that QRICH1 and ATF4 modulate tRNA metabolic processes to promote secreted protein synthesis during ER stress. | SIGNOR-269406 |
P14921 | P24821 | 1 | transcriptional regulation | up-regulates quantity by expression | 0.2 | Sp1 and Ets1 are potent transactivators of the TN-C promoter. | SIGNOR-261599 |
P25098 | Q16539 | 1 | phosphorylation | down-regulates | 0.2 | Phosphorylation of p38 by grk2 at the docking groove unveils a novel mechanism for inactivating p38mapk p38 associates with grk2 endogenously and is phosphorylated by grk2 at thr-123, a residue located at its docking groove. Mimicking phosphorylation at this site impairs the binding and activation of p38 by mkk6 and diminishes the capacity of p38 to bind and phosphorylate its substrates | SIGNOR-150152 |
Q9UNN5 | Q7Z434 | 1 | binding | down-regulates activity | 0.2 | We find that the scaffold protein FAF1 forms aggregates that negatively regulate MAVS.FAF1 antagonizes the poly-ubiquitination and aggregation of MAVS by competing with TRIM31 for MAVS association. | SIGNOR-277619 |
O60260 | P49792 | 1 | ubiquitination | down-regulates quantity by destabilization | 0.2 | Our findings suggested that the intracellular levels of RanBP2 and its functional activity may be modulated by Parkin-mediated ubiquitination and proteasomal pathways. Furthermore, Parkin controls the intracellular levels of sumoylated HDAC4, as a result of the ubiquitination and degradation of RanBP2. | SIGNOR-259116 |
Q99856 | P0DOX3 | 1 | transcriptional regulation | up-regulates quantity by expression | 0.2 | In this work, we show that TFII-I directly interacts with human Bright through amino acids in Bright's protein interaction domain and that specific tyrosine residues of TFII-I are essential for Bright-induced activity of an immunoglobulin reporter gene. Moreover, inhibition of TFII-I function in a B-cell line resulted in decreased heavy-chain transcript levels.| Figure 3 shows that both anti-Bright and anti-TFII-I precipitated the bf150 Bright binding site from the B-cell line but not from a T-cell line that contains but does not express the V1 gene. | SIGNOR-268531 |
P25103 | P38405 | 1 | binding | up-regulates activity | 0.2 | Here we systematically quantified ligand-induced interactions between 148 GPCRs and all 11 unique G alpha subunit C-termini. For each receptor, we probed chimeric G alpha subunit activation via a transforming growth factor-alpha (TGF alpha) shedding response in HEK293 cells lacking endogenous Gq/11- and G12/13- signaling. | We defined positive coupling if any member of the subfamily scored LogRAi ≥ -1 and negative coupling if all of the members scored LogRAi < -1 (Figure 3A-B). ROC analysis gives AUC = 0.78 (Figure S4A) when considering high-confidence known coupling data and suggested a threshold of LogRAi ≥ -1.0 for defining true couplings. | The score associated to this interaction has a LogRAi ≥ -1.0. | SIGNOR-256919 |
P37275 | P09467 | 1 | transcriptional regulation | down-regulates quantity by repression | 0.2 | Down-regulation of FBP1 by ZEB1-mediated repression confers to growth and invasion in lung cancer cells|we confirmed DNA methylation in the promoter contributed to the decrease of FBP1 expression in lung cancer cells. We identified Zinc finger E-box-binding homeobox 1 (ZEB1) bond to FBP1 promoter to enhance DNA methylation in lung cancer cells. | SIGNOR-267596 |
P35367 | P09471 | 1 | binding | up-regulates activity | 0.2 | Here we systematically quantified ligand-induced interactions between 148 GPCRs and all 11 unique G alpha subunit C-termini. For each receptor, we probed chimeric G alpha subunit activation via a transforming growth factor-alpha (TGF alpha) shedding response in HEK293 cells lacking endogenous Gq/11- and G12/13- signaling. | We defined positive coupling if any member of the subfamily scored LogRAi ≥ -1 and negative coupling if all of the members scored LogRAi < -1 (Figure 3A-B). ROC analysis gives AUC = 0.78 (Figure S4A) when considering high-confidence known coupling data and suggested a threshold of LogRAi ≥ -1.0 for defining true couplings. | The score associated to this interaction has a LogRAi ≥ -1.0. | SIGNOR-257251 |
P18848 | P49591 | 1 | transcriptional regulation | up-regulates quantity by expression | 0.2 | QRICH1 promotes the expression of translation-related genes. our combined ChIP-seq and RNA-seq analyses identified that QRICH1 and ATF4 were enriched at the promoters of these specific tRNA synthetases, and that ER stress positively regulated their transcription (Fig. 4I). Together, these findings suggest that QRICH1 and ATF4 modulate tRNA metabolic processes to promote secreted protein synthesis during ER stress. | SIGNOR-269424 |
Q96L34 | Q13470 | 1 | phosphorylation | down-regulates activity | 0.2 | We also discover a MARK-mediated phosphorylation on TNK1 at S502 that promotes an interaction between TNK1 and 14-3-3, which sequesters TNK1 and inhibits its kinase activity.Phosphorylation of TNK1 at S502 within the proline rich domain is required for TNK1 binding to 14-3-3.MARKs mediate phosphorylation at S502 and 14-3-3 binding to TNK1, which restrains the movement of TNK1 into heavy membrane-associated clusters. | SIGNOR-273865 |
Q15077 | P63092 | 1 | binding | up-regulates activity | 0.2 | Here we systematically quantified ligand-induced interactions between 148 GPCRs and all 11 unique G alpha subunit C-termini. For each receptor, we probed chimeric G alpha subunit activation via a transforming growth factor-alpha (TGF alpha) shedding response in HEK293 cells lacking endogenous Gq/11- and G12/13- signaling. | We defined positive coupling if any member of the subfamily scored LogRAi ‚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-256804 |
P49591 | P01106 | 1 | binding | down-regulates activity | 0.2 | Using in vitro, cell and animal experiments, we show here that SerRS intervenes by antagonizing c-Myc, the major transcription factor promoting VEGFA expression, through a tandem mechanism. First, by direct head-to-head competition, nuclear-localized SerRS blocks c-Myc from binding to the VEGFA promoter. Second, DNA-bound SerRS recruits the SIRT2 histone deacetylase to erase prior c-Myc-promoted histone acetylation. | SIGNOR-259368 |
O75030 | Q15661 | 1 | transcriptional regulation | up-regulates quantity by expression | 0.2 | The transcription of tryptase gene in human mast cells is regulated by mi transcription factor |Using mutant constructs of tryptase promoter, we observed that two E-box (CANNTG) motifs including between -817 to -715 and -421 to -202 are able to involve in the transactivation of tryptase gene by MITF-A. | SIGNOR-251725 |
P68400 | Q01534 | 1 | phosphorylation | up-regulates activity | 0.2 | CK2-dependent C-terminal phosphorylation at T300 directs the nuclear transport of TSPY protein | SIGNOR-250969 |
Q9BV47 | P11362 | 1 | dephosphorylation | down-regulates activity | 0.2 | NEAP and DUSP26 dephosphorylated TrkA and FGFR1 directly.|We found that NEAP, but not its phosphatase-defective mutant, suppressed nerve growth factor (NGF) receptor TrkA and fibroblast growth factor receptor 1 (FGFR1) activation in PC12 cells | SIGNOR-277104 |
Q14980 | Q13509 | 1 | binding | up-regulates | 0.2 | Direct binding of numa to tubulin is mediated by a novel sequence motif in the tail domain that bundles and stabilizes microtubules. | SIGNOR-116979 |
Q96TA1 | P01112 | 1 | binding | up-regulates activity | 0.2 | EGFR phosphorylates FAM129B, resulting in binding of phosphorylated FAM129B to H-Ras and reduced the association of p120-RasGAP with H-Ras, thereby enhancing H-Ras activation for ERK1/2-dependent β-catenin transactivation for enhanced Warburg effect, tumor cell proliferation, and brain tumorigenesis. | SIGNOR-273659 |
P29466 | Q96EP0 | 2 | cleavage | down-regulates activity | 0.2 | We show that LUBAC interacted with caspase-1 via HOIP and modified its CARD domain with linear polyubiquitin and that depletion of HOIP or Sharpin resulted in heightened caspase-1 activation and cell death in response to inflammasome activation, unlike what is observed in macrophages. Reciprocally, caspase-1, as well as caspase-8, regulated LUBAC activity by proteolytically processing HOIP at Asp-348 and Asp-387 during the execution of cell death. | SIGNOR-272193 |
Q9BXC1 | P63092 | 1 | binding | up-regulates activity | 0.2 | Here we systematically quantified ligand-induced interactions between 148 GPCRs and all 11 unique G alpha subunit C-termini. For each receptor, we probed chimeric G alpha subunit activation via a transforming growth factor-alpha (TGF alpha) shedding response in HEK293 cells lacking endogenous Gq/11- and G12/13- signaling. | We defined positive coupling if any member of the subfamily scored LogRAi ‚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-256757 |
Q03135 | P43005 | 1 | binding | down-regulates activity | 0.2 | EAAT3 has previously been shown to form complexes with caveolin-1, a major component of caveolae, which participate in the regulation of transport proteins. The present study explored the impact of caveolin-1 on electrogenic transport by excitatory amino acid transporter isoforms EAAT1-4. caveolin-1 is a powerful negative regulator of the excitatory glutamate transporters EAAT1, EAAT2, EAAT3, and EAAT4. Caveolin-1 has been shown to form complexes with the excitatory amino acid transporter EAAT3 (EAAC1) (Gonzalez et al. 2007) and may thus modify the EAAT isoforms by direct interaction with the carriers. | SIGNOR-264807 |
P17612 | Q9Y6D6 | 1 | phosphorylation | up-regulates activity | 0.2 | Within 20 min after addition of 8-Br-cAMP, BIG1 accumulated in nuclei, and this effect was blocked by protein kinase A (PKA) inhibitors H-89 and PKI, suggesting a dependence on PKA-catalyzed phosphorylation. |Mutant BIG1 (S883A) in which Ala replaced Ser-883, a putative PKA phosphorylation site, did not move to the nucleus with cAMP addition, whereas replacement with Asp (S883D) resulted in nuclear accumulation of BIG1 without or with cAMP exposure, consistent with the mechanistic importance of a negative charge at that site | SIGNOR-272146 |
P0C0S8 | Q5FBB7 | 1 | relocalization | 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.|The centromeric localization of Sgo1 requires histone H2A phosphorylation at T120 (H2A-pT120) by the kinase Bub1. | SIGNOR-265262 |
Q8N0X7 | Q96J02 | 2 | binding | up-regulates activity | 0.2 | Cytosolic endogenous spartin is mono-ubiquitinated and we demonstrate that it interacts via a PPXY motif with the ubiquitin E3 ligases AIP4 [atrophin-interacting protein 4; ITCH (itchy E3 ubiquitin protein ligase homologue] [corrected] and AIP5 (WWP1). Surprisingly, the PPXY motif, AIP4 and AIP5 are not required for spartin's ubiquitination, and so we propose that spartin acts as an adaptor for these proteins. | SIGNOR-261306 |
Q7LBC6 | P25874 | 1 | transcriptional regulation | up-regulates quantity by expression | 0.2 | We show that Jhdm2a expression is induced by beta-adrenergic stimulation, and that Jhdm2a directly regulates peroxisome proliferator-activated receptor alpha (Ppara) and Ucp1 expression. | SIGNOR-266638 |
P35398 | Q8IVA1 | 1 | transcriptional regulation | up-regulates quantity by expression | 0.2 | RORα regulates the expression of several genes in Purkinje cells. RORα becomes highly expressed in postmitotic Purkinje cells. It regulates their maturation, particularly dendritic differentiation. Dendritogenesis and the expression of several genes, including Shh, Itpr1, Pcp4, Calb1, Pcp2, and Slc1a6, normally expressed in mature Purkinje cells, are inhibited in RORα-deficient mice. | SIGNOR-266849 |
P49840 | Q969R2 | 1 | phosphorylation | up-regulates activity | 0.2 | CK1a1, JNK1 and CDK1 had the highest site-specific activity for ORP4L, while CDK1, GSK3a, CK1a1 and GSK3b showed the highest specificity for the site when corrected for background activity with ORP4L-S4A. Because of the complexity of the serine/proline-rich site, we did not determine which serine(s) in ORP4L were phosphorylated by candidate kinases.|We conclude that phosphorylation of a unique serine/proline motif in the ORD induces a conformation change in ORP4L that enhances interaction with vimentin and cholesterol extraction from membranes. | SIGNOR-264875 |
Q14493 | P0C0S8 | 1 | translation regulation | up-regulates quantity by expression | 0.2 | Synthesis of mature histone mRNA requires only a single processing reaction: an endonucleolytic cleavage between a conserved stem-loop and a purine-rich downstream element to form the 3' end. The stem-loop binding protein (SLBP) is required for processing, and following processing, histone mRNA is transported to the cytoplasm, where SLBP participates in translation of the histone mRNA|We used radiolabeled probes generated by PCR targeting the open reading frame (ORF) to detect histones H2A, H2B, H3, H4, and H1 and used 7SK snRNA as a loading control (Fig. 2A). The abundance of histone H2A, H2B, H3, and H4 mRNAs is reduced to 37% to 70% of control levels in the SLBP knockdown cells when compared to the C2 control. | SIGNOR-265403 |
Q13315 | Q9NPI1 | 1 | phosphorylation | down-regulates activity | 0.2 | ATM Directly Phosphorylates BRD7 at Ser 263 Site. | SIGNOR-279780 |
Q9H3F6 | Q8IW35 | 1 | binding | down-regulates quantity by destabilization | 0.2 | Cullin-3-KCTD10-mediated CEP97 degradation promotes primary cilium formation. we identified the cullin-3-RBX1-KCTD10 complex as the E3 ligase that mediates CEP97 degradation and removal from the mother centriole. | SIGNOR-272923 |
Q9NQU5 | P04049 | 1 | phosphorylation | up-regulates activity | 0.2 | PAK5 phosphorylates Raf-1 on serine 338 and stimulates Raf-1 activity. | SIGNOR-278971 |
O60260 | Q07817 | 1 | ubiquitination | down-regulates quantity by destabilization | 0.2 | In cells, we found BCL-XL levels were reduced by overexpression of PARK2, but this catalytic activity was blocked by the proteasome inhibitor MG132, suggesting degradation of BCL-XL protein by PARK2 is dependent on the proteasome system (XREF_FIG A).|PARK2 directly binds to and ubiquitinates BCL-XL. | SIGNOR-278661 |
Q9HAZ1 | O75030 | 1 | phosphorylation | down-regulates quantity by destabilization | 0.2 | Mechanistically, wild type CLK4 (WT-CLK4) but not kinase-dead CLK4-K189R mutant phosphorylated MITF at Y360. This modification promoted its interaction with E3 ligase COP1 and its K63-linked ubiquitination at K308/K372, leading to sequestosome 1 recognition and autophagic degradation. | SIGNOR-274116 |
Q5JXC2 | Q04206 | 1 | binding | 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-273829 |
P18146 | P10645 | 1 | transcriptional regulation | up-regulates quantity by expression | 0.2 | Recently, binding of specific protein 1 (Sp1) and cAMP response element binding protein (CREB) to a GC-rich element at -92/-62 has been identified as a critical step in gastrin-dependent regulation of the chromogranin A (CgA) gene in gastric epithelial cells. Here we demonstrate that binding of early growth response protein 1 (Egr-1) to the distal part of the -92/-62 site is also required for gastrin-dependent CgA transactivation. | SIGNOR-254265 |
P43657 | P63096 | 1 | binding | up-regulates activity | 0.2 | Here we systematically quantified ligand-induced interactions between 148 GPCRs and all 11 unique G alpha subunit C-termini. For each receptor, we probed chimeric G alpha subunit activation via a transforming growth factor-alpha (TGF alpha) shedding response in HEK293 cells lacking endogenous Gq/11- and G12/13- signaling. | We defined positive coupling if any member of the subfamily scored LogRAi ≥ -1 and negative coupling if all of the members scored LogRAi < -1 (Figure 3A-B). ROC analysis gives AUC = 0.78 (Figure S4A) when considering high-confidence known coupling data and suggested a threshold of LogRAi ≥ -1.0 for defining true couplings. | The score associated to this interaction has a LogRAi ≥ -1.0. | SIGNOR-256725 |
P23470 | P52630 | 1 | dephosphorylation | up-regulates activity | 0.2 | 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-254728 |
P17612 | Q6PIY7 | 1 | phosphorylation | down-regulates activity | 0.2 | We found that Gld2 activity is regulated by site-specific phosphorylation in its disordered N-terminal domain. We identified two phosphorylation sites (S62, S110) where phosphomimetic substitutions increased Gld2 activity and one site (S116) that markedly reduced activity. Using mass spectrometry, we confirmed that HEK 293 cells readily phosphorylate the N-terminus of Gld2. We identified protein kinase A (PKA) and protein kinase B (Akt1) as the kinases that site-specifically phosphorylate Gld2 at S116, abolishing Gld2-mediated nucleotide addition. | SIGNOR-259402 |
O60260 | Q8IXI2 | 1 | ubiquitination | down-regulates quantity by destabilization | 0.2 | We observe that Parkin efficiently ubiquitylates Miro1 at highly conserved lysine residues, 153, 230, 235, 330 and 572, upon phosphorylation by PINK1. | SIGNOR-278561 |
O15530 | P05129 | 1 | phosphorylation | up-regulates | 0.2 | One of the most studiedevents controlled by ptdins(3,4,5)p3, comprises the activation of aof agc family protein kinases, including isoforms of protein kinase b (pkb)/akt, p70 ribosomal s6 kinase (s6k), serum- and glucocorticoid-induced protein kinase (sgk) and protein kinase c (pkc), which play crucial roles in regulating physiological processes relevant to metabolism, growth, proliferation and survival. Here, we review recent biochemical, genetic and structural studies on the 3-phosphoinositide-dependent protein kinase-1 (pdk1), which phosphorylates and activates the agc kinase members regulated by pi 3-kinase. We also discuss whether inhibitors of pdk1 might have chemotherapeutic potential in the treatment of cancers in which the pdk1-regulated agc kinases are constitutively activated. | SIGNOR-126072 |
Q8N0X7 | Q9H0M0 | 1 | binding | up-regulates activity | 0.2 | Cytosolic endogenous spartin is mono-ubiquitinated and we demonstrate that it interacts via a PPXY motif with the ubiquitin E3 ligases AIP4 [atrophin-interacting protein 4; ITCH (itchy E3 ubiquitin protein ligase homologue] [corrected] and AIP5 (WWP1). Surprisingly, the PPXY motif, AIP4 and AIP5 are not required for spartin's ubiquitination, and so we propose that spartin acts as an adaptor for these proteins. | SIGNOR-261307 |
P36888 | P24752 | 1 | phosphorylation | up-regulates activity | 0.2 | We previously reported that the mitochondrial fraction of FLT3 activates acetyl-CoA acetyltransferase ACAT1 in mitochondria via Y407 phosphorylation to acetylate and inhibit mitochondrial pyruvate dehydrogenase A (PDHA) and PDH phosphatase 1 (PDP1) | SIGNOR-267628 |
P53350 | Q9NYQ6 | 1 | phosphorylation | down-regulates activity | 0.2 | In contrast to the non autonomous polarity defects caused by transgenic expression of Celsr1 LLtoAA, Plk1 inhibition did not cause a significant alteration in Celsr1 interphase polarity (XREF_FIG).|Plk1 phosphorylates the Celsr1 cytoplasmic domain in\nvitro . | SIGNOR-279094 |
P31749 | Q8N9L9 | 1 | phosphorylation | up-regulates quantity by stabilization | 0.2 | HSPA1A was found to associate with ACOT4. Furthermore, we found that phosphorylation of ACOT4 at S392 by AKT decreased the binding of ACOT4 to HSPA1A, resulting in ACOT4 accumulation. |AKT phosphorylates ACOT4 at S392 and promotes ACOT4 stability | SIGNOR-271820 |
Q5D1E8 | P17542 | 1 | post transcriptional regulation | up-regulates quantity | 0.2 | Here, we show that Regnase-1 regulates self-renewal of HSPCs through modulating the stability of Gata2 and Tal1 mRNA | SIGNOR-259944 |
P53778 | Q16875 | 1 | phosphorylation | up-regulates quantity | 0.2 | KRAS transformation and overexpression of p38gamma increased expression of PFKFB3 and glucose transporter GLUT2 | SIGNOR-279539 |
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