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 |
|---|---|---|---|---|---|---|---|
P08047 | P49585 | 1 | transcriptional regulation | up-regulates quantity by expression | 0.2 | Sp1 and Sp3 function as transcriptional activators of the Ctpct promoter | SIGNOR-266231 |
Q15326 | P84243 | 1 | binding | up-regulates activity | 0.2 | We found that full-length BS69 specifically interacted with H3K36me3 in native nucleosome co-immunoprecipitation (co-IP) experiments. We propose that BS69 specifically associates with H3K36me3-enriched chromatin through the PWWP domain, which facilitates the recruitment of MYND-bound transcription and chromatin remodeling factors including EZH2, HDAC1, Brg1 and E2F6 to target gene loci, thereby repressing target gene transcription. | SIGNOR-263897 |
P48730 | P02810 | 1 | phosphorylation | up-regulates | 0.2 | Ser22 may be phosphorylated by a g-ck that recognizes an atypical substrate sequence or by a novel kinase. While prp1 secreted from salivary glands is fully phosphorylated at ser8 and 22 | SIGNOR-75272 |
Q8TCQ1 | P13762 | 1 | polyubiquitination | down-regulates quantity by destabilization | 0.2 | Two E3 ligases, MARCH I and MARCH VIII, have been shown to polyubiquitinate lysine residue 225 in the cytoplasmic tail of I-Abeta and HLA-DRbeta. We show that lysine residue 219 in the cytoplasmic tail of DRalpha is also subject to polyubiquitination. | SIGNOR-271409 |
Q92831 | Q71DI3 | 1 | acetylation | down-regulates activity | 0.2 | The HAT module within the SAGA and ADA complexes acetylates histone H3, mainly on residues K9 and K14. | SIGNOR-269626 |
P23470 | O75553 | 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-254697 |
Q8NHG7 | Q9Y468 | 1 | binding | down-regulates activity | 0.2 | In response to DNA damage, VCP/p97, an ATPase which unfolds proteins, removes L3MBTL1 from H4K20me2, creating free H4K20me2 for 53BP1 to bind to (Fig. 3b). | SIGNOR-262060 |
Q6ZWJ1 | P46937 | 1 | binding | down-regulates activity | 0.2 | WW domain‐containing protein STXBP4 inhibits YAP activity via LATS1‐mediated phosphorylation. | SIGNOR-260013 |
P0DMV8 | P22413 | 1 | post transcriptional regulation | up-regulates quantity | 0.2 | We demonstrated the binding of heat shock protein 70 (HSP70) to ENPP1-3'UTR. Through this binding, HSP70 stabilizes ENPP1 mRNA and increases ENPP1 transcript and protein levels. This positive modulation of ENPP1 expression is paralleled by a reduced insulin-induced IR and IRS-1 phosphorylation. | SIGNOR-252197 |
P54792 | P17252 | 1 | binding | up-regulates | 0.2 | Our findings suggest a molecular interaction between pka, hdpr1, and dvl and a possible contribution of this interaction to tumorigenesis. | SIGNOR-199454 |
Q86YJ5 | Q13291 | 1 | ubiquitination | down-regulates quantity by destabilization | 0.2 | MARCH9, a member of the RING-CH family of transmembrane E3 ubiquitin ligases, down-regulates CD4, major histocompatibility complex-I (MHC), and ICAM-1 in lymphoid cells. To identify novel MARCH9 substrates, we used high throughput flow cytometry and quantitative mass spectrometry by stable isotope labeling by amino acids in cell culture (SILAC) to determine the differential expression of plasma membrane proteins in a MARCH9-expressing B cell line. This combined approach identified 13 potential new MARCH9 targets. | SIGNOR-271537 |
O14965 | Q14863 | 1 | phosphorylation | down-regulates activity | 0.2 | Here, we report that Aurora kinase A phosphorylates mPOU at Ser197 and inhibit its DNA-binding ability. | SIGNOR-273546 |
Q14493 | Q7L7L0 | 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-265409 |
O15033 | O75431 | 1 | ubiquitination | down-regulates quantity by destabilization | 0.2 | Therefore, these results implied that AREL1 ubiquitinates and promotes the degradation of MTX2. | SIGNOR-267674 |
Q70YC5 | P09874 | 1 | binding | up-regulates activity | 0.2 | We identified ZNF365 as a necessary component of the HR repair pathway. ZNF365 interacts with PARP1 and tethers MRE11 to the nucleolytic resection sites for replication fork recovery | SIGNOR-272477 |
P28370 | Q9NRC1 | 1 | transcriptional regulation | down-regulates quantity by repression | 0.2 | Human SWI/SNF-associated PRMT5 methylates histone H3 arginine 8 and negatively regulates expression of ST7 and NM23 tumor suppressor genes. | SIGNOR-268991 |
Q13131 | P52292 | 1 | phosphorylation | up-regulates | 0.2 | Ampk phosphorylated importin alpha1 on ser(105). Accordingly, expression of importin alpha1 proteins bearing k22r or s105a mutations failed to mediate the nuclear import of hur in intact cells. Our results point to importin alpha1 as a critical downstream target of ampk and key mediator of ampk-triggered hur nuclear import. | SIGNOR-128629 |
Q9BQN1 | Q8N752 | 1 | binding | up-regulates quantity | 0.2 | We identified members of the FAM83 family of proteins as partners of CK1 in cells. All eight members of the FAM83 family (FAM83A–H) interacted with the α and α-like isoforms of CK1; FAM83A, -B, -E, and -H also interacted with the δ and ε isoforms of CK1. The intrinsic catalytic activity of CK1 is not affected by or required for the association of CK1 with FAM83 proteins. Our findings imply that the DUF1669 domains of FAM83 proteins anchor CK1 α, α-like, δ, and ε isoforms in specific subcellular compartments and potentially mediate their association with substrates. | SIGNOR-273760 |
O96013 | O43426 | 1 | phosphorylation | up-regulates activity | 0.2 | We identified two novel Pak5 substrates, Pacsin1 and Synaptojanin1, proteins that directly interact with one another to regulate synaptic vesicle endocytosis and recycling. Pacsin1 and Synaptojanin1 were phosphorylated by Pak5 and the other group II Paks in vitro, and Pak5 phosphorylation promoted Pacsin1-Synaptojanin1 binding both in vitro and in vivo. | SIGNOR-263024 |
Q6PML9 | P49757 | 1 | ubiquitination | down-regulates quantity by destabilization | 0.2 | Lnx functions as a ring type e3 ubiquitin ligase that targets the cell fate determinant numb for ubiquitin-dependent degradation. | SIGNOR-113704 |
Q6UB99 | Q9BR76 | 1 | transcriptional regulation | up-regulates quantity by expression | 0.2 | Neurite growth-related genes such as Trkb, Bdnf, Gap43, Coronin 1B, and Rab13 are downregulated in ANKRD11-deficient neurons. | SIGNOR-266737 |
Q08117 | Q96F45 | 1 | binding | down-regulates activity | 0.2 | these results show that Grg5 can specifically interact with the C-terminus of Nolz1. these data suggest that Nolz1 functions as a repressor molecule, and that Grg5 interactions with Nolz1 serve to modulate Nolz1 repressor function. Mechanistically, Grg5 is known to modulate Grg co-repressor activity, raising the possibility that classical Grg proteins mediate Nolz1-dependent transcriptional repression. GalNolz1ΔC22 showed increased repressor activity compared with GalNolz1, consistent with the ability of Grg5 to modulate Nolz1 repressor function. | SIGNOR-261192 |
Q06187 | Q06187 | 2 | phosphorylation | up-regulates | 0.2 | Overexpression of btk with a src family kinase increases tyrosine phosphorylation and catalytic activity of btk. This occurs by transphosphorylation at y551 in the btk catalytic domain and the enhancement of btk autophosphorylation at a second site. We mapped the major btk autophosphorylation site to y223 within the sh3 domain | SIGNOR-41480 |
P17252 | P11387 | 1 | phosphorylation | up-regulates activity | 0.2 | In vitro kinase assays demonstrated that Ser(10) can be phosphorylated by casein kinase II, Ser(21) can be phosphorylated by protein kinase Calpha, and Ser(112) and Ser(394) can be phosphorylated by Cdk1.Collectively these results indicate that topo I is phosphorylated during mitosis at multiple sites, one of which enhances DNA relaxation activity in vitro and interaction with DNA in cells. | SIGNOR-276154 |
P68400 | P49418 | 1 | phosphorylation | down-regulates | 0.2 | Amphiphysins interact directly with clathrin and have a function in clathrin-mediated synaptic vesicle recycling and clathrin-mediated endocytosis. The n-terminal domain of clathrin bound to unphosphorylated amphiphysin-1, but not to the phosphorylated protein. The assumption that casein kinase 2 phosphorylates amphiphysin-1 at t350 and t387 was corroborated by experiments showing that: casein kinase 2 phosphorylated these residues directly in vitro,. upon activation by nerve growth factor, casein kinase 2 phosphorylates amphiphysin-1 and thereby regulates the endocytosis of clathrin-coated vesicles via the interaction between clathrin and amphiphysin. | SIGNOR-149314 |
P17612 | P54296 | 1 | phosphorylation | down-regulates | 0.2 | This binding is regulated in vitro by phosphorylation of a single serine residue (ser76) in the immediately adjacent amino-terminal domain mp1. M-protein phosphorylation by camp-dependent kinase a inhibits binding to myosin lmm. | SIGNOR-56395 |
Q9Y5I2 | Q9Y5G5 | 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-265702 |
Q13131 | Q8NE86 | 1 | phosphorylation | up-regulates activity | 0.2 | Cellular ATP levels drop during early mitosis, and the mitochondrial Ca2+ transients boost mitochondrial respiration to restore energy homeostasis. This is achieved through mitosis-specific MCU phosphorylation and activation by the mitochondrial translocation of energy sensor AMP-activated protein kinase (AMPK). |In vitro kinase assays showed that AMPK immunoprecipitated from cells as well as recombinant AMPK phosphorylated MCU at Ser57 | SIGNOR-275547 |
O14490 | Q9BYB0 | 1 | relocalization | up-regulates activity | 0.2 | SHANK proteins are ‘master’ scaffolding proteins that tether and organize intermediate scaffolding proteins. They are located at excitatory synapses, where they are crucial for proper synaptic development and function. SAPAP proteins subsequently bind to the PDZ domain of members of the SHANK protein family. SHANK proteins then bind to the actin cytoskeleton and to Homer protein, which in turn interacts with mGluRs. Through these extended links, PSD95, SAPAP, SHANK and Homer proteins form a quaternary complex that brings together mGluR and NMDAR complexes in the PSD (FIG. 3). | SIGNOR-264588 |
O43829 | O43829 | 2 | binding | up-regulates activity | 0.2 | ZF5, which we have cloned as a transcriptional repressor on the mouse c-myc promoter, has the POZ domain at the amino-terminus and the Kruppel-type zinc finger domain at the carboxy-terminus. We demonstrated that the POZ domain has a function mediating homomeric protein-protein interaction and this interaction requires the zinc finger domain. | SIGNOR-220534 |
Q04206 | P12644 | 1 | transcriptional regulation | down-regulates quantity by repression | 0.2 | Co-transfection with pCMV4-RelA alone or in combination with pCMV4p50 repressed pSLA4.1 EX-Lux activity by approximately 75 percent in both H441 and A549 cells | SIGNOR-266087 |
Q9UGL1 | P84243 | 1 | demethylation | up-regulates activity | 0.2 | KDM5 subfamily is capable of removing tri‐ and di‐ methyl marks from lysine 4 on histone H3 (H3K4). Depending on the methylation site, its effect on transcription can be either activating or repressing. | SIGNOR-264304 |
O00206 | O00206 | 2 | binding | up-regulates | 0.2 | Upon activation, tlrs hetero- or homodimerize inducing the recruitment of adaptor proteins via the cytoplasmic tir domain | SIGNOR-203484 |
P10909 | O14920 | 1 | binding | down-regulates quantity by destabilization | 0.2 | CLU-2 is a ubiquitin binding protein (UBP) that enhances proteasome activity. sCLU promotes degradation of COMMD1. sCLU interacts with the SCF-βTrCP E3 ligase complex, serving as a scaffolding chaperone to form a multimeric protein complex that facilitates COMMD1 and I-κB ubiquitination and proteasomal degradation. | SIGNOR-271433 |
Q92794 | P10147 | 1 | transcriptional regulation | up-regulates quantity by expression | 0.2 | We further demonstrate that the histone acetyltransferase, MOZ, can activate the MIP-1a promoter in T-cells and that this activation is largely dependent upon the proximal RUNX site. Moreover, we show that co-expression of MOZ and RUNX1 can activate the MIP-1a promoter. | SIGNOR-251726 |
P83916 | Q16695 | 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-264492 |
P35222 | O95388 | 1 | transcriptional regulation | up-regulates quantity | 0.2 | This study identifies WISP-1 as a beta-catenin-regulated gene that can contribute to tumorigenesis. The promoter of WISP-1 was cloned and shown to be activated by both Wnt-1 and beta-catenin expression. | SIGNOR-256270 |
P00519 | O60260 | 1 | phosphorylation | down-regulates | 0.2 | Here we show that the nonreceptor tyrosine kinase c-abl phosphorylates tyrosine 143 of parkin, inhibiting parkin's ubiquitin e3 ligase activity and protective function. | SIGNOR-167853 |
Q12857 | Q9Y6N7 | 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-268893 |
O60858 | O60858 | 2 | polyubiquitination | down-regulates quantity by destabilization | 0.2 | In this study, we showed that the N-degron pathway mediates ubiquitin (Ub)-dependent reticulophagy. During this 2-step process, the ER transmembrane E3 ligase TRIM13 undergoes auto-ubiquitination via lysine 63 (K63) linkage chains and acts as a ligand for the autophagic receptor SQSTM1/p62 (sequestosome 1). | SIGNOR-272219 |
P25098 | P41143 | 1 | phosphorylation | down-regulates activity | 0.2 | Taken together, we have demonstrated that agonist-induced opioid receptor phosphorylation occurs exclusively at two phosphate acceptor sites (T358 and S363) of GRK2 at the DOR carboxyl terminus. | SIGNOR-249660 |
P18848 | P49588 | 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-269414 |
Q13131 | P06400 | 1 | phosphorylation | down-regulates | 0.2 | Amp-activated protein kinase phosphorylates retinoblastoma protein. Rb phosphorylation sites, ser804 (ser811 in human), resembled the ampk consensus phosphorylation site. | SIGNOR-184052 |
Q9UL15 | O60260 | 1 | binding | down-regulates activity | 0.2 | Here, we show that BAG5, a BAG domain-containing family member, interacts with both Hsp70 and parkin with deleterious functional consequences. Through these interactions, BAG5 inhibits Hsp70 chaperone activity and parkin E3 ubiquitin ligase activity Immunoprecipitation (IP) of GFP-parkin resulted in the coimmunoprecipitation of both Hsp70 and BAG5 or BAG5(DARA) (Figure 4A). Furthermore, IP of GFP-parkin resulted in the coimmunoprecipitation of BAG5 or BAG5 (DARA) in the absence of overexpressed Hsp70. Taken together, these data demonstrate that BAG5 can directly inhibit parkin-mediated autoubiquitinylation independently of Hsp70. | SIGNOR-261198 |
P68400 | P53539 | 1 | phosphorylation | up-regulates | 0.2 | Our findings indicate that ck2 activation increases deltafosb's transactivation potential, while ck2 inhibition decreases it. Further, we show that preventing ser27 phosphorylation by mutating the site to ala results in a significant decrease in deltafosb transactivation | SIGNOR-152403 |
O75665 | O75143 | 1 | binding | down-regulates quantity by destabilization | 0.2 | The OFD1 protein inhibits autophagosome biogenesis by selective autophagy-mediated degradation of Autophagy Related 13 (ATG13), a component of the unc-51-like kinase (ULK1) autophagy initiation complex. | SIGNOR-269107 |
P12643 | P12643 | 2 | binding | up-regulates | 0.2 | Bmps are dimeric proteins with a single interchain disulfide bond. The dimeric conformation is an absolute requirement for the biological action and interaction with receptors | SIGNOR-236166 |
O60502 | P08237 | 1 | deglycosylation | up-regulates activity | 0.2 | Our previous investigation on O-GlcNAcylation of PFK1 has demonstrated that O-GlcNAcylation inhibits PFK1 enzyme activity|In cells, a single set of antagonistic enzymes-O-GlcNAc transferase (OGT) and O-GlcNAc hydrolase are responsible for the addition and removal of GlcNAc moiety, respectively. | SIGNOR-267607 |
P62987 | O60260 | 1 | binding | up-regulates activity | 0.2 | The phosphorylation-dependent interaction between ubiquitin and parkin suggests that phosphorylated ubiquitin unlocks autoinhibition of the catalytic cysteine. Our results show that PINK1-dependent phosphorylation of both parkin and ubiquitin is sufficient for full activation of parkin E3 activity. These findings demonstrate that phosphorylated ubiquitin is a parkin activator. | SIGNOR-270344 |
Q14686 | Q4ZG55 | 1 | transcriptional regulation | up-regulates quantity by expression | 0.2 | Herein, using growth-regulating estrogen receptor binding 1 (GREB1) as an ERα target gene in Ishikawa cells, we demonstrate that nuclear receptor co-activator 6 (NCOA6) is essential for estradiol (E2)/ERα-activated GREB1 transcription. We found that NCOA6 associates with the GREB1 promoter and enhancer in an E2-independent manner and that NCOA6 knockout reduces chromatin looping, enhancer-promoter interactions, and basal GREB1 expression in the absence of E2. | SIGNOR-265883 |
P53567 | Q9NPD5 | 1 | transcriptional regulation | up-regulates quantity by expression | 0.2 | Taken together, these findings suggest that the LPS-induced down-regulation of Oatp4 is likely due to reduction in the binding of HNF1alpha, C/EBP, HNF3, and RXR:RAR to the Oatp4 promoter. | SIGNOR-268986 |
Q92890 | Q9UKV5 | 1 | binding | up-regulates activity | 0.2 | Here we show that Ufd1 directly interacts with gp78 and functions as a cofactor. Ufd1 enhances the E3 activity of gp78, accelerates the ubiquitination and degradation of reductase, and eventually promotes receptor-mediated uptake of low-density lipoprotein. | SIGNOR-252425 |
Q9UNE7 | Q99828 | 1 | ubiquitination | down-regulates quantity | 0.2 | All those were suggesting that CHIP promotes CIB1 ubiquitination via the Lys 48 residue of ubiquitin.|K10 and K65 were the Lysine (K) residues for CHIP mediated CIB1 degradation. | SIGNOR-278721 |
Q9BYB0 | P42263 | 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-264603 |
P14373 | O75385 | 1 | ubiquitination | down-regulates quantity | 0.2 | STK38L ubiquitination promotes its activation and phosphorylation of ULK1 at Ser495, rendering ULK1 in a permissive state for TRIM27-mediated hyper-ubiquitination | SIGNOR-270349 |
P27361 | Q9BZI1 | 1 | phosphorylation | up-regulates activity | 0.2 | To identify the phosphorylated residue, we introduced a serine-to-alanine substitution at residues 294 and 326 and a threonine-to-alanine substitution at residue 331 in Irx2(291–356). Erk1 phosphorylated S294A and T331A, but not S326A (Fig. 4b), indicating that Ser326 is the bona fide MAP kinase target. | SIGNOR-263061 |
P42229 | Q9NPD5 | 1 | transcriptional regulation | up-regulates quantity by expression | 0.2 | PRL enhanced the binding of Stat5a to the OATP1B3 promoter and DNA-protein binding was inhibited in competition assays by excess OATP1B3 and Stat5 consensus oligomers but not by mutant Stat5 oligomers.|PRL and GH induction of Oatp1b2 and OATP1B3 promoter activity required cotransfection of Stat5a and PRLRL or GHR. | SIGNOR-268990 |
P80192 | P80192 | 2 | phosphorylation | up-regulates activity | 0.2 | We present here biochemical and biophysical evidence that MLK1 is activated by autophosphorylation in (or near) the activation loop. The activation loops of the MLK family are highly homologous, and so one might predict that the same residues would be key to their activation. Functional data presented here, however, demonstrate that the key residue for activation of MLK1, Thr312, differs from the key residue for activation of MLK3. | SIGNOR-249388 |
Q96BR1 | Q86YD1 | 1 | phosphorylation | down-regulates quantity by destabilization | 0.2 | In this study, we find that the understudied serum and glucocorticoid-induced kinase-2 (SGK2) phosphorylates PTOV1 at S36. | SIGNOR-279283 |
P49841 | E9PAV3 | 1 | phosphorylation | down-regulates | 0.2 | Gsk3 beta-dependent phosphorylation of the alpha nac coactivator regulates its nuclear translocation and proteasome-mediated degradation. | SIGNOR-123262 |
P0C0S8 | Q8IYW5 | 1 | binding | up-regulates | 0.2 | Rnf168 is recruited to sites of dna damage by binding to ubiquitylated histone h2a. | SIGNOR-183890 |
Q9UBY8 | Q01105 | 1 | binding | down-regulates activity | 0.2 | CLN8 interacts with ceramide binding proteins PP2A and I2PP2A. We showed that the phosphorylation levels of several substrates of PP2A, namely Akt, S6 kinase, and GSK3β, were decreased in CLN8 disease patient fibroblasts. This reduction can be reversed by inhibiting PP2A phosphatase activity with cantharidin, suggesting a higher PP2A activity in CLN8-deficient cells. The phosphorylation levels of PP2A substrates are decreased in the absence of CLN8. | SIGNOR-265584 |
Q9Y4C1 | Q16695 | 1 | demethylation | up-regulates activity | 0.2 | Using a biochemical assay coupled with chromatography, we have purified a JmjC domain-containing protein, JHDM2A, which specifically demethylates mono- and dimethyl-H3K9. | SIGNOR-276846 |
P54829 | Q16611 | 1 | dephosphorylation | up-regulates activity | 0.2 | In this study, we report that on apoptotic stimulation Bak undergoes dephosphorylation at tyrosine residue 108 (Y108), a critical event that is necessary but not sufficient for Bak activation, but is required both for early exposure of the occluded N-terminal domain and multimerisation. | SIGNOR-248542 |
P17612 | Q9NRM7 | 1 | phosphorylation | up-regulates | 0.2 | Here, we show that cyclic amp (camp)-dependent protein kinase (pka) phosphorylates lats and thereby enhances its activity sufficiently to phosphorylate yap on ser381. | SIGNOR-236994 |
P59637 | O00560 | 1 | relocalization | up-regulates activity | 0.2 | Overall, these results support the hypothesis that the interaction of E protein PBM with syntenin facilitates the recruitment of syntenin in the cytosol and leads to p38 MAPK activation. | SIGNOR-260752 |
P17612 | O14558 | 1 | phosphorylation | down-regulates | 0.2 | Hosphorylation of hsp20 at ser16 is not only associated with cyclic nucleotide-dependent vasorelaxation but also inhibits agonist-induced contractile responses. | SIGNOR-66493 |
P16591 | P16591 | 2 | phosphorylation | up-regulates activity | 0.2 | Mutation analysis unveiled a tyrosine (Tyr(616)) embedded in the Hsp90 recognition loop, which is required for the kinase activity of Fer. Replacement of this tyrosine by phenylalanine (Y616F) disabled the auto-phosphorylation activity of Fer and abolished its ability to phosphorylate Stat3. | SIGNOR-276236 |
P00533 | Q8TDY4 | 1 | phosphorylation | up-regulates activity | 0.2 | How ACAP4 regulates membrane dynamics and curvature in response to EGF stimulation is unknown. Here, we show that phosphorylation of the N-terminal region of ACAP4, named the Bin, Amphiphysin, and RSV161/167 (BAR) domain, at Tyr34 is necessary for EGF-elicited membrane remodeling. |EGF stimulation of cells causes phosphorylation of ACAP4 at Tyr34, which subsequently promotes ACAP4 homodimer curvature. | SIGNOR-272234 |
O95153 | Q9UQ26 | 1 | binding | down-regulates activity | 0.2 | SH3 domains of RBPs interact with RIMs. The enhancement of depolarization-induced secretion in PC12 cells by fusion proteins that suppress the associations of RBPs with RIMs and α1 suggests that RBPs may repress RIMs, either directly or through associated proteins. | SIGNOR-264368 |
Q12852 | O14950 | 1 | phosphorylation | up-regulates | 0.2 | Zip kinase (hzipk) phosphorylated the regulatory light chain of myosin ii (mrlc) at both ser19 and thr18 in vitro. In this study, we demonstrate that hzipk also induces the diphosphorylation of mrlc in nonmuscle cells. | SIGNOR-113664 |
P24666 | P31751 | 1 | dephosphorylation | down-regulates activity | 0.2 | Reduction in the levels of both LMW-PTP isoforms in vitro and in vivo increased tyrosine phosphorylation of IR and AktSer473 and increased IRS-1- and IRS-2-associated PI3-K activities in both liver and fat.|Activated PI3-K stimulates Akt (or protein kinase B) that in turn phosphorylates and inactivates glycogen synthase kinase-3 | SIGNOR-248456 |
P17509 | P69905 | 1 | transcriptional regulation | down-regulates quantity by repression | 0.2 | HOXB6 protein represses globin transcript levels in stably transfected K562 cells in a DNA-binding dependent fashion. | SIGNOR-261637 |
P17252 | Q9NQA5 | 1 | phosphorylation | up-regulates activity | 0.2 | A cell permeable analog of DAG increased TRPV5 activity within 30 min via protein kinase C activation of the channel since mutation of TRPV5 at the putative PKC phosphorylation sites S299 and S654 prevented the stimulatory effect of TK. | SIGNOR-149948 |
P43405 | Q8TB45 | 1 | phosphorylation | down-regulates activity | 0.2 | We found that tyrosine (Tyr) 289 phosphorylation of DEPTOR impairs its interaction with mTOR, leading to increased mTOR activation. Using proximity biotinylation assays, we identified SYK (spleen tyrosine kinase) as a kinase involved in DEPTOR Tyr 289 phosphorylation in an ephrin (erythropoietin-producing hepatocellular carcinoma) receptor-dependent manner. | SIGNOR-277572 |
Q13131 | P11908 | 1 | phosphorylation | down-regulates activity | 0.2 | We demonstrate here that glucose deprivation or hypoxia results in the AMPK-mediated phosphorylation of phosphoribosyl pyrophosphate synthetase 1 (PRPS1) S180 and PRPS2 S183, leading to conversion of PRPS hexamers to monomers and thereby inhibiting PRPS1/2 activity, nucleotide synthesis, and nicotinamide adenine dinucleotide (NAD) production. | SIGNOR-265731 |
Q9P253 | Q9NYY3 | 1 | ubiquitination | down-regulates quantity by destabilization | 0.2 | VPS18 Ubiquitylates SNK in Vitro and in Vivo. The ubiquitylation of proteins by hVPS18 was selectively mediated by UbcH4. | SIGNOR-271550 |
Q05655 | P11413 | 1 | phosphorylation | up-regulates | 0.2 | A pkc activator, significantly increased g6pd phosphorylation and activity, whereas single (s210a, t266a) and double (s210a/t266a) mutations at sites flanking the g6pd active site significantly inhibited phosphorylation, shifted the isoelectric point, and reduced enzyme activity. | SIGNOR-167053 |
Q13177 | Q99523 | 1 | phosphorylation | down-regulates activity | 0.2 | PAKs specifically phosphorylate Ser15 of the sortilin-cd and alter its trafficking. It can be concluded that PAK1-3 may indeed instigate the phosphorylation of sortilin and that they target a single serine residue (Ser15) located in the kinase domain-binding site of the sortilin-cd. Full-length sortilins with the serine at position 793 (residue 15 in the cytoplasmic domain) (for the sequence, see Fig. 2). Phosphorylation (Ser15) downregulates the sortilin–AP-1 interaction. | SIGNOR-273717 |
P54646 | Q9H2X6 | 1 | phosphorylation | down-regulates activity | 0.2 | AMPKalpha2-mediated inhibition of WIP1 phosphorylation by HIPK2|Site-directed mutagenesis of Thr112 and Ser114 in the N terminus, and Thr1107 in the C terminus markedly reduced HIPK2 phosphorylation by AMPKalpha2 in vitro | SIGNOR-275485 |
P43405 | Q32MZ4 | 1 | phosphorylation | up-regulates activity | 0.2 | However, this inhibitory activity TRIP can be reversed by the co-expression of Syk, which might inhibit the activity of cytoplasmic TRIP, sequester TRIP from important nucleolar targets or even counter TRIP 's inhibitory effects on TRAF and TNF signaling by regulating the activity of alternative components of the pathway.|Syk induces phosphorylation of TRIP on tyrosine. | SIGNOR-279297 |
P56915 | Q15375 | 1 | transcriptional regulation | down-regulates quantity by repression | 0.2 | We demonstrate that Goosecoid can act as a repressor of its own promoter activity in transient co-transfection experiments in mouse P19 cells and in Xenopus embryos. Autorepression depends on the presence of the homeodomain and is mediated through the prd element more proximal to the transcriptional start site. | SIGNOR-261613 |
O60858 | P04234 | 1 | polyubiquitination | down-regulates quantity by destabilization | 0.2 | RFP2, a gene frequently lost in various malignancies, encodes a protein with RING finger, B-box, and coiled-coil domains that belongs to the RBCC/TRIM family of proteins.Rfp2 Regulates the Stability of the ERAD Substrate CD3-δ. In summary, these experiments demonstrate that Rfp2 functions as a RING-dependent ERAD E3 ubiquitin ligase and regulates the degradation of the ER substrate, CD3-δ. | SIGNOR-271644 |
P17252 | P48050 | 1 | phosphorylation | down-regulates activity | 0.2 | These results therefore indicate that Kir2.3 is directly modulated by PKC phosphorylation of its channel protein and threonine 53 is the PKC phosphorylation site in Kir2.3. | SIGNOR-275965 |
Q96GD4 | P10412 | 1 | phosphorylation | up-regulates quantity by stabilization | 0.2 | we showed previously that phosphorylation of S27 in human histone H1.4 (H1.4S27-P), prevents binding of heterochromatin protein 1 (HP1) family members (officially known as chromobox protein homologs) to the neighboring dimethylated K26. Here, we present the first functional characterization of H1.4S27-P in vivo and in vitro. We show that H1.4S27 phosphorylation is cell-cycle-regulated and its levels peak on metaphase chromosomes. We identify further Aurora B as the kinase phosphorylating H1.4S27. | SIGNOR-262658 |
Q9NXA8 | P07195 | 1 | deacetylation | up-regulates activity | 0.2 | In colorectal cancer, SIRT5 binds to lactate dehydrogenase B (LDHB) to deacetylate it at Lysine 329, thereby increasing its enzymatic activity. | SIGNOR-267645 |
Q5XX13 | P04406 | 1 | polyubiquitination | up-regulates activity | 0.2 | Mechanistically, FBXW10 promotes GAPDH polyubiquitination and activation; VRK2-dependent phosphorylation of GAPDH Ser151 residue is critical for GAPDH ubiquitination and activation. | SIGNOR-277841 |
Q00535 | O75962 | 1 | phosphorylation | up-regulates activity | 0.2 | Roscovitine inhibits the ability of Trio to activate Rac, and peptides corresponding to the Cdk5 consensus sites in Trio are phosphorylated by Cdk5.|Together, these data suggest that control of the cortical actin cytoskeleton, long known to modulate hormone exocytosis and subsequent endocytosis, involves Cdk5 mediated activation of Trio. | SIGNOR-280220 |
Q00535 | P47989 | 1 | phosphorylation | up-regulates activity | 0.2 | Finally, threonine 222 of XOR is the critical target site for CDK5 dependent activation of XOR.|Once we determined CDK5 was necessary for hypoxia induced hyperactivation of XOR, we tested whether CDK5 was sufficient to phosphorylate XOR and induce increased enzymatic activity in a cell free system. | SIGNOR-280221 |
Q13315 | Q9HAU4 | 1 | phosphorylation | up-regulates activity | 0.2 | Using biochemical approaches and MS analysis, we show that upon the onset of the DNA-damage response, SMURF2 becomes phosphorylated at Ser384 by ataxia telangiectasia mutated (ATM) serine/threonine kinase, and this phosphorylation is required for its interaction with RNF20. | SIGNOR-277534 |
Q9UHD2 | P11908 | 1 | phosphorylation | up-regulates activity | 0.2 | Here, we show that ionizing radiation results in TBK1-mediated phosphorylation of phosphoribosyl pyrophosphate synthetase (PRPS)1/2 at T228, thereby enhancing PRPS1/2 catalytic activity and promoting deoxyribonucleotide synthesis. | SIGNOR-277317 |
O15054 | P68431 | 1 | demethylation | down-regulates activity | 0.2 | Ubiquitously Transcribed Tetratricopeptide Repeat on chromosome X (UTX) and Jumonji D3 (JMJD3) as novel histone demethylases that catalyze the removal of di- and trimethyl groups on histone H3 lysine 27, thereby promoting target gene activation. | SIGNOR-260018 |
P48730 | P11308 | 1 | phosphorylation | down-regulates activity | 0.2 | Interestingly, only CKId, but not other CKI isoforms or CKII could promote ERG degradation under ectopic expression conditions (XREF_FIG).|These results indicate that phosphorylation of ERG by CKIdelta within the SPOP-recognition degron triggers its interaction with SPOP to promote ERG destruction . | SIGNOR-280234 |
P47900 | 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-257185 |
Q15208 | Q9BXF6 | 1 | phosphorylation | up-regulates activity | 0.2 | We identified 5 potential NDR1 substrates in the mouse brain and chose two for functional validation. We show that one NDR1 substrate is another kinase, AP-2 associated kinase-1 (AAK1) which regulates dendritic branching as a result of NDR1 phosphorylation. Another substrate is the Rab8 guanine nucleotide exchange factor (GEF) Rabin8 (a Sec2p homolog) which we find is involved in spine synapse formation. | SIGNOR-263035 |
P24941 | P24941 | 2 | phosphorylation | up-regulates | 0.2 | Our results demonstrate that cdk2 is capable of autophosphorylation at thr160. | SIGNOR-153636 |
P14921 | Q9Y458 | 1 | transcriptional regulation | up-regulates quantity by expression | 0.2 | TBX22 is an X-linked gene, which encodes a T-box-containing transcription factor. Loss-of-function mutation in the X-linked TBX22 promoter disrupts an ETS-1 binding site and leads to cleft palate. We first link the transcription factor ETS-1 to TBX22 pathway during embryonic palatogenesis. | SIGNOR-265565 |
Q9BTA9 | P53350 | 1 | binding | up-regulates activity | 0.2 | Here, we report that the activation of Plk1 requires WAC, a WW domain-containing adaptor protein with a coiled-coil region that predominantly localizes to the nucleus in interphase. Cyclin-dependent kinase 1 (Cdk1) phosphorylates WAC, priming its direct interaction with the polo-box domain of Plk1. | SIGNOR-265036 |
Q9HCP0 | P07948 | 1 | phosphorylation | up-regulates quantity by stabilization | 0.2 | Although there have been more than 40 reports of mass spectrometric studies on phosphorylation at Lyn-S13, the kinase responsible remained unclear. We succeeded in identifying casein kinase 1γ (CK1γ) as the kinase responsible for phosphorylation of Lyn-S13. In HEK293 cells co-expressing Lyn and CK1γ, the phosphorylation level of Lyn-S13 increased significantly. we concluded that S-palmitoylated CK1γ encounters N-myristoylated Lyn and specifically phosphorylates the Ser-13 residue at the Golgi during intracellular protein traffic, as shown schematically in Fig. 8. Phosphorylated dual-lipid-modified Lyn and S-palmitoylated CK1γ are then transported from the Golgi to the plasma membrane. | SIGNOR-275396 |
Q8NA31 | P54274 | 1 | relocalization | up-regulates activity | 0.2 | The shelterin complex has six proteins, containing TRF1, TRF2, POT1, RAP1, TIN2, and TPP1. The shelterin complex is localized to the chromosome end and protects telomeric DNA (Palm and de Lange, 2008). The TTM complex acts as a “linker” and bridges the LINC and shelterin complexes together. The connection between TTM and shelterin complexes is well-known, which is mediated by TERB1 and TRF1 | SIGNOR-263315 |
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