IdA stringlengths 6 21 | IdB stringlengths 6 21 | labels int64 0 2 | mechanism stringclasses 40
values | effect stringclasses 10
values | score float64 0.1 0.99 ⌀ | sentence stringlengths 10 1.63k ⌀ | signor_id stringlengths 12 14 |
|---|---|---|---|---|---|---|---|
Q9Y2Y9 | P45984 | 0 | phosphorylation | down-regulates quantity by destabilization | 0.2 | TGF-β-mediated downregulation of KLF13 by HDAC-mediated epigenetic silencing and JNK-induced phosphorylation abrogates the latter’s inhibitory effect on TGF-β signaling. | SIGNOR-277809 |
P06241 | Q15700 | 1 | phosphorylation | up-regulates activity | 0.367 | Recombinant PSD-93 was phosphorylated by Fyn in vitro, and Tyr-384 was identified as a major phosphorylation site. In COS7 cells, exogenously expressed PSD-93 was phosphorylated, dependent on its membrane localization. In addition, tyrosine-phosphorylated PSD-93 was able to bind to Csk, a negative regulator of Src fami... | SIGNOR-262874 |
P30556 | P04201 | 2 | binding | down-regulates activity | 0.276 | our findings demonstrate that the protein encoded by the Mas proto-oncogene exhibits direct antagonistic properties on the AT1 receptor in vitro and that this oligomeric interaction may represent a natural state for these receptors in vivo in some tissues. the present findings in native tissues suggest that the Mas rec... | SIGNOR-260626 |
P51452 | Q05397 | 1 | dephosphorylation | down-regulates activity | 0.326 | Deficiency in VHR/DUSP3, a suppressor of focal adhesion kinase, reveals its role in regulating cell adhesion and migration.|In vitro assays proved that recombinant VHR directly dephosphorylated FAK and paxillin. | SIGNOR-277033 |
Q05655 | P62714 | 0 | dephosphorylation | down-regulates activity | 0.3 | PP2A(c) displayed the highest specific activity towards PKCdelta. The role of PP2A(c) in the dephosphorylation of PKCdelta in cells was supported by the demonstration that these proteins could be co-immunoprecipitated from NIH3T3 cells.|In conclusion, the evidence here indicates that PKCdelta de-phosphorylation and hen... | SIGNOR-248595 |
P28482 | P19484 | 1 | phosphorylation | down-regulates activity | 0.413 | Evidence for ERK2-mediated TFEB phosphorylation came from ERK2-TFEB coimmuno-precipitation (fig. S12C) in normal but not in starved medium and from a peptide-based kinase assay showing that mutation of Ser142 to alanine abolished ERK2-mediated phosphorylation ( | SIGNOR-248279 |
P0DTC6 | P52292 | 2 | binding | down-regulates activity | 0.2 | The results from Figure 1C suggest that ORF6 inhibits IFN-β production through IRF3 or a component downstream of IRF3. Thus, we examined the effect of ORF6 on IRF3 nuclear translocation. Upon poly(I:C) treatment, IRF3 translocated to the cell nucleus in the absence of ORF6, whereas the expression of ORF6 blocked its nu... | SIGNOR-262513 |
Q8N137 | P53350 | 0 | phosphorylation | up-regulates activity | 0.324 | However, unlike NEK2, PLK1 phosphorylation enhances the microtubule stabilizing activity of centrobin [22].|PLK1 phosphorylation of centrobin is critical for bipolar spindle formation. | SIGNOR-279551 |
O94806 | Q8WYL5 | 1 | phosphorylation | down-regulates activity | 0.286 | Active PKD Isoforms Phosphorylate and Inactivate SSH1L|Here, we show that active PKD3 also mediates SSH1L phosphorylation at Ser-978 and binding to 14-3-3, further confirming the involvement of all three PKD isoforms in negatively regulating this phosphatase | SIGNOR-275938 |
Q13224 | P54829 | 0 | dephosphorylation | down-regulates activity | 0.547 | These previous results, together with the present findings, indicate that STEP61 dephosphorylates the NR2B subunit at its regulatory tyr1472 site, and dephosphorylation of this site leads to internalization of the NMDAR complex from neuronal surface membranes. | SIGNOR-265744 |
P35813 | Q86WV6 | 1 | dephosphorylation | down-regulates activity | 0.2 | Collectively, our findings suggest that the overexpression of PPM1A antagonizes the STING- and TBK1-induced type I interferon signaling pathway.|First, PPM1A directly dephosphorylated STING, likely via its S358 site (Figs.|Moreover, our study demonstrates that while TBK1 enhances STING aggregation in a kinase activity-... | SIGNOR-276958 |
Q14582 | P61244 | 2 | binding | up-regulates activity | 0.482 | the role MAX plays in transcription is thought to be primarily as a cofactor for DNA binding. In this capacity, however, it appears to be essential for most, if not all, the known biological activities of MYC. MAX also functions as a cofactor for DNA binding for a group of bHLHZip proteins related to MYC, including MNT... | SIGNOR-240224 |
Q8N2W9 | P15927 | 1 | phosphorylation | up-regulates | 0.2 | Pias1 and pias4 promote brca1 accumulation and sumoylation, rpa phosphorylation, and dsb repair furthermore, phosphorylation of the 34 kda subunit of rpa on ser-4 and ser-8 (ps4/ps8) in response to ir or camptothecin treatment was diminished by pias4 depletion, while pias1 depletion impaired ir-induced but not camptot... | SIGNOR-162164 |
Q9BYP7 | Q9UHW9 | 1 | phosphorylation | down-regulates activity | 0.444 | WNK3, which inhibits the activity of KCC3, promoted phosphorylation of Ser-96 as well as Thr-991 and Thr-1048. | SIGNOR-260912 |
P10827 | P28702 | 2 | binding | up-regulates | 0.649 | Like many receptors belonging to the superfamily of steroid/thyroid nuclear receptors, thyroid hormone receptors (trs) bind to specific th-dna responsive elements (tre) upstream of target gene in heterodimeric complex with the 9-cis retinoid acid receptor (rxr | SIGNOR-81452 |
Q12851 | Q13233 | 2 | binding | up-regulates | 0.565 | The mekk1 associated with the gck carboxyl terminus is catalytically active. | SIGNOR-59682 |
O60346 | P23443 | 1 | dephosphorylation | down-regulates activity | 0.572 | Here we report the identification of ribosomal protein S6 kinase 1 (S6K1) as a novel substrate of PHLPP. | SIGNOR-237454 |
P18825 | P63096 | 2 | binding | up-regulates activity | 0.48 | Here we systematically quantified ligand-induced interactions between 148 GPCRs and all 11 unique G alpha subunit C-termini. For each receptor, we probed chimeric G alpha subunit activation via a transforming growth factor-alpha (TGF alpha) shedding response in HEK293 cells lacking endogenous Gq/11- and G12/13- signali... | SIGNOR-256699 |
P49715 | Q06945 | 1 | transcriptional regulation | down-regulates | 0.382 | In summary, our data demonstrate that C/EBPα negatively regulates Sox4 transcription via direct DNA-binding. | SIGNOR-255675 |
Q13501 | P00533 | 0 | phosphorylation | down-regulates activity | 0.33 | Here we found that EGFR-stimulated phosphorylation of SQSTM1 at tyrosine 433 induces dimerization of its UBA domain, which disturbs the sequestration function of SQSTM1 and causes autophagic flux blocking. | SIGNOR-277500 |
O95644 | Q9P1W9 | 0 | phosphorylation | up-regulates activity | 0.261 | In addition to PIM1, also PIM2 and PIM3 were able to phosphorylate WT, but not MM NFATC1 in vitro (Fig. (Fig.22c). | SIGNOR-276772 |
O75496 | O43791 | 0 | ubiquitination | down-regulates activity | 0.2 | SPOP promotes K27-linked non-degradative poly-ubiquitination of Geminin at lysine residues 100 and 127. This poly-ubiquitination of Geminin prevents DNA replication over-firing by indirectly blocking the association of Cdt1 with the MCM protein complex, an interaction required for DNA unwinding and replication. | SIGNOR-268926 |
P08069 | P27986 | 2 | binding | up-regulates | 0.718 | Igf-1 activated both the pi3k and the extracellular signal-regulated kinase [?] (erk [?]) Pathways as evidenced by phosphorylation of either akt or erk1 [?]/2 (respectively) | SIGNOR-179386 |
O60674 | Q9UQC2 | 1 | phosphorylation | up-regulates | 0.515 | In vitro, activated jak2 directly phosphorylated specific gab2 tyrosine residues. Mutagenesis studies revealed that gab2 tyrosine 643 (y643) was a major target of jak2 in vitro, and a key residue for jak2-dependent phosphorylation in intact cells. Mutation of gab2 y643 inhibited g-csf-stimulated erk1/2 activation and s... | SIGNOR-179488 |
Q13555 | Q9UQD0 | 1 | phosphorylation | up-regulates activity | 0.271 | CaMKII enhances voltage-gated sodium channel Nav1.6 activity and neuronal excitability|mmobilized peptide arrays and nanoflow LC-electrospray ionization/MS of Nav1.6 reveal potential sites of CaMKII phosphorylation, specifically Ser-561 and Ser-641/Thr-642 within the first intracellular loop of the channel. | SIGNOR-275794 |
Q9Y2K2 | O15055 | 1 | phosphorylation | down-regulates quantity by destabilization | 0.2 | In the current study, we found that SIK3 promotes phosphorylation of PER2 and regulates the abundance of the protein by accelerating its degradation. | SIGNOR-279570 |
P07585 | P08254 | 0 | cleavage | down-regulates quantity by destabilization | 0.673 | Degradation of decorin by matrix metalloproteinases. These data indicate proteolytic degradation of DCN by MMP-2, MMP-3 and MMP-7, and suggest the possibility that, under pathophysiological conditions, the digestion by the MMPs may induce tissue reactions mediated by TGF-beta1 released from DCN in the connective tissu... | SIGNOR-256353 |
Q8N122 | Q9NQL2 | 2 | binding | up-regulates | 0.905 | Active rag and gtr heterodimers are able to bind and activate torc1, through direct interactions with raptor | SIGNOR-162093 |
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 |
P09471 | P18089 | 2 | binding | up-regulates activity | 0.31 | Here we systematically quantified ligand-induced interactions between 148 GPCRs and all 11 unique G alpha subunit C-termini. For each receptor, we probed chimeric G alpha subunit activation via a transforming growth factor-alpha (TGF alpha) shedding response in HEK293 cells lacking endogenous Gq/11- and G12/13- signali... | SIGNOR-256993 |
P48730 | Q5T0W9 | 2 | 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 req... | SIGNOR-273766 |
P21333 | P45985 | 2 | binding | up-regulates activity | 0.523 | We used Filamin-A-deficient cells to show that Filamin A enhances MKK7 activation and is important for synergistic stress-induced JNK activation in vivo. Thus Filamin A is a novel member of the group of scaffold proteins whose function is to link two MAPKKs together and promote JNK activation. The present study provide... | SIGNOR-260629 |
P46937 | Q15831 | 0 | phosphorylation | down-regulates activity | 0.305 | LKB1 induces phosphorylation of Yap, leading to Yap nuclear exclusion and ultimately its degradation.|These data indicated that LKB1 expression inhibits Yes-associated protein transcriptional function. | SIGNOR-280139 |
P26010 | Q99704 | 2 | binding | down-regulates activity | 0.324 | 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-257695 |
P24941 | Q9UGP5 | 1 | phosphorylation | up-regulates quantity by stabilization | 0.335 | Phosphorylation of DNA polymerase λ is required to maintain its stability. Recently, we identified Pol lambda as an interaction partner of cyclin-dependent kinase 2 (CDK2) that is central to the cell cycle G1/S transition and S-phase progression. Experiments with phosphorylation-defective mutants suggest that phosphor... | SIGNOR-276169 |
Q6R327 | P49841 | 0 | phosphorylation | down-regulates quantity by destabilization | 0.409 | We show that this process is dependent on glycogen synthase kinase 3 (GSK3): GSK3 was associated with rictor and directly phosphorylated the Thr-1695 site in a putative CDC4 phospho-degron motif of rictor; mutation of this site impaired the interaction between rictor and FBXW7, decreased rictor ubiquitination, and incr... | SIGNOR-276898 |
Q00987 | O60858 | 0 | polyubiquitination | down-regulates quantity by destabilization | 0.374 | Here, we demonstrate that overexpression of RFP2 in cells induced apoptosis through proteasomal degradation of MDM2 and AKT. We observed that RFP2 formed a complex with MDM2, a negative regulator of the p53 tumor suppressor, and AKT, a regulator of apoptosis inhibition at the cellular level. Additionally, we found tha... | SIGNOR-271851 |
Q05655 | P67775 | 0 | dephosphorylation | down-regulates activity | 0.377 | PP2A(c) displayed the highest specific activity towards PKCdelta. The role of PP2A(c) in the dephosphorylation of PKCdelta in cells was supported by the demonstration that these proteins could be co-immunoprecipitated from NIH3T3 cells.|In conclusion, the evidence here indicates that PKCdelta de-phosphorylation and hen... | SIGNOR-248638 |
P01111 | Q7Z5G4 | 0 | palmitoylation | up-regulates activity | 0.396 | Covalent lipid modifications mediate the membrane attachment and biological activity of Ras proteins. All Ras isoforms are farnesylated and carboxyl-methylated at the terminal cysteine; H-Ras and N-Ras are further modified by palmitoylation. Here we report that H- and N-Ras are palmitoylated by a human protein palmito... | SIGNOR-261354 |
Q13422 | P67870 | 0 | phosphorylation | down-regulates | 0.2 | We identified four novelikarosphosphorylation sites that are phosphorylated by ck2 kinase. / ck2-mediated phosphorylation inhibits ikaros' localization to pc-hc / hyperphosphorylation of ikaros promotes its degradation by the ubiquitin/proteasome pathway | SIGNOR-174844 |
P60891 | Q9NRM7 | 0 | phosphorylation | down-regulates quantity by destabilization | 0.2 | Recruitment of TRAF2 to PRPS1/2 requires phosphorylation of PRPS1 S285 or PRPS2 T285, which is mediated by low stiffness-activated large tumor suppressor (LATS)1/2 kinases.LATS1/2-dependent S/T285 phosphorylation is required for PRPS1/2 ubiquitination and degradation at low stiffness. | SIGNOR-276504 |
P38405 | P28336 | 2 | binding | up-regulates activity | 0.278 | Here we systematically quantified ligand-induced interactions between 148 GPCRs and all 11 unique G alpha subunit C-termini. For each receptor, we probed chimeric G alpha subunit activation via a transforming growth factor-alpha (TGF alpha) shedding response in HEK293 cells lacking endogenous Gq/11- and G12/13- signali... | SIGNOR-256918 |
O60656 | P20823 | 0 | transcriptional regulation | up-regulates quantity by expression | 0.267 | Using gel shift and functional assays, HNF1alpha was demonstrated to bind to and activate the UGT1A8, -1A9, and -1A10 promoters. In contrast, Cdx2 bound to and activated the UGT1A8 and -1A10 promoters but could not activate the UGT1A9 promoter. | SIGNOR-253973 |
P98077 | P00533 | 2 | binding | up-regulates | 0.611 | Shc exists in three different isoforms, p46shc, p52shc and p66shc which are tyrosine phosphorylated upon egf stimulation and bind to the activated egfr and grb2. Interestingly, while the 46 and 52 kda isoforms increase mitogenic signalling after egf stimulation and are able to transform nih3t3 cells (pelicci et al. 199... | SIGNOR-107750 |
P25021 | P63096 | 2 | binding | up-regulates activity | 0.25 | Here we systematically quantified ligand-induced interactions between 148 GPCRs and all 11 unique G alpha subunit C-termini. For each receptor, we probed chimeric G alpha subunit activation via a transforming growth factor-alpha (TGF alpha) shedding response in HEK293 cells lacking endogenous Gq/11- and G12/13- signali... | SIGNOR-257049 |
Q99708 | Q96T58 | 2 | binding | down-regulates | 0.542 | We identify the ctip and ctbp corepressors as novel components of the human rbp-jk/sharp-corepressor complex and show that ctip binds directly to the sharp repression domain. | SIGNOR-141616 |
Q9UBX2 | P78337 | 1 | transcriptional regulation | up-regulates quantity by expression | 0.307 | DUX4, a candidate gene of facioscapulohumeral muscular dystrophy, encodes a transcriptional activator of PITX1 | SIGNOR-261590 |
P04637 | O14920 | 0 | phosphorylation | up-regulates activity | 0.52 | Here , we show that IKKbeta modulates the activity of p53 in response to glutamine depletion to promote cancer cell adaptation .|Taken together, these results indicate that IKK\u03b2 phosphorylates p53 on Ser392 as an early response to glutamine deprivation and possibly later facilitates its phosphorylation at Ser15 an... | SIGNOR-278516 |
Q15139 | O15264 | 0 | phosphorylation | down-regulates | 0.2 | P38delta catalyzes an inhibitory phosphorylation of pkd1, thereby attenuating stimulated insulin secretion. | SIGNOR-183280 |
P46531 | P53350 | 0 | phosphorylation | down-regulates quantity by destabilization | 0.402 | As shown in Fig. S4D, the C-terminal NOTCH1 fragment was readily phosphorylated by PLK1. Additionally, when the two putative phosphorylation sites, Ser-1791 and Ser-2349, were replaced by Ala, WT NOTCH1-IC but not the mutant was efficiently phosphorylated (Fig. S4E). We found that mutation of Ser-1791/2349 promotes NOT... | SIGNOR-277491 |
P43034 | P07900 | 2 | binding | up-regulates quantity by stabilization | 0.522 | The type I lissencephaly gene product LIS1, a key regulator of cytoplasmic dynein, is critical for cell proliferation, survival, and neuronal migration. However, little is known about the regulation of LIS1. Here, we identify a previously uncharacterized mammalian homolog of Aspergillus NudC, NudCL2 (NudC-like protein ... | SIGNOR-252168 |
O60260 | P42566 | 1 | ubiquitination | up-regulates | 0.2 | Treatment of cells with egf stimulates parkin binding to both eps15 and the egfr and promotes parkin-mediated ubiquitination of eps15 | SIGNOR-148218 |
P15941 | P43403 | 0 | phosphorylation | up-regulates activity | 0.448 | Indeed, the present results demonstrate that ZAP-70 phosphorylates MUC1-CD and that the MUC1-CD Y-20 site functions, at least in part, as a ZAP-70 substrate (Fig. 4C). In this regard, the in vivo phosphorylation data indicate that ZAP-70 may also contribute to phosphorylation of MUC1-CD Y-46.The results further show th... | SIGNOR-247039 |
P25098 | P18545 | 1 | phosphorylation | up-regulates activity | 0.2 | Mutation of Thr-62 (to Ala) in PDEgamma produced a GRK2 phosphorylation-resistant mutant that was less effective in associating with GRK2 in response to epidermal growth factor and did not potentiate the stimulation of p42/p44 mitogen-activated protein kinase by this growth factor. | SIGNOR-247823 |
P12931 | O43255 | 1 | phosphorylation | up-regulates activity | 0.334 | In human breast cancer cell lines, the protein kinase Src has been shown to activate Siah2 by phosphorylation of tyrosines 86, 140, and 263.|This function is promoted by Src phosphorylation of Siah2, which increases C/EBPdelta binding, ubiquitination, and degradation. | SIGNOR-279555 |
P60953 | Q9P107 | 0 | gtpase-activating protein | down-regulates activity | 0.512 | We therefore developed a screening-compatible live-cell imaging assay, using FRET-based biosensors for the prototype GTPases RHOA, RAC1 and CDC4215,19,20 (Extended Data Fig. 2 and Supplementary Note 1)|We found catalytic activities for 45/75 RhoGEFs and 48/63 RhoGAPs| Our data thus not only reveal extensive promiscuity... | SIGNOR-260507 |
Q13627 | Q52LA3 | 1 | phosphorylation | up-regulates activity | 0.681 | Here we report that DYRK1A can specifically phosphorylate LIN52 on serine residue 28, and that this phosphorylation is required for DREAM assembly. | SIGNOR-262846 |
P41279 | P53350 | 1 | phosphorylation | up-regulates | 0.2 | Xplkk1 phosphorylates and activates mammalian plk / xplkk1 phosphorylates thr-210 | SIGNOR-92274 |
P01112 | Q06124 | 0 | dephosphorylation | up-regulates activity | 0.681 | Here we identify SHP2 as the ubiquitously expressed tyrosine phosphatase that preferentially binds to and dephosphorylates Ras to increase its association with Raf and activate downstream proliferative Ras/ERK/MAPK signalling. | SIGNOR-252094 |
Q9NY46 | P61328 | 2 | binding | down-regulates activity | 0.235 | 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-253444 |
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 |
P28482 | Q12913 | 0 | dephosphorylation | down-regulates | 0.406 | In this study we show that one of these potential targets, the erk1/2, is indeed a direct dep-1 substrate in vivo. | SIGNOR-161536 |
Q9Y5H6 | P05556 | 2 | binding | up-regulates activity | 0.2 | The clustered protocadherins comprise the largest subfamily of the cadherin superfamily and are predominantly expressed in the nervous system. Pcdh-alpha proteins interact with beta1-integrin to promote cell adhesion. | SIGNOR-265671 |
Q16539 | Q12888 | 1 | phosphorylation | down-regulates activity | 0.28 | Here we show that 53BP1 is phosphorylated during mitosis on two residues, T1609 and S1618, located in its well-conserved ubiquitination-dependent recruitment (UDR) motif.|Dephosphorylation enables the recruitment of 53BP1 to double-strand DNA breaks |phosphorylation of T1609 is likely to be mediated by p38 MAPK | SIGNOR-264446 |
O14965 | O96028 | 1 | phosphorylation | up-regulates quantity by stabilization | 0.2 | Mechanistically, Aurora A phosphorylated NSD2 at S56 residue to protect the protein from cleavage and degradation, thus methylation of Aurora A and phosphorylation of NSD2 bilaterally formed a positive regulating loop. | SIGNOR-275512 |
P00533 | P09874 | 1 | phosphorylation | up-regulates activity | 0.394 | EGFR and MET heterodimer interacts with and phosphorylates PARP1. | SIGNOR-279169 |
Q13309 | Q13485 | 1 | ubiquitination | down-regulates | 0.397 | We found that skp2, the f-box component of scfskp2, physically interacted with smad4 at the physiological levels. Several cancer-derived unstable mutants exhibited significantly increased binding to skp2, which led to their increased ubiquitination and accelerated proteolysis. These results suggest an important role fo... | SIGNOR-127964 |
P68400 | P52952 | 1 | phosphorylation | up-regulates activity | 0.332 | Mutational analysis and in vitro kinase assays suggested that this 40-kDa Csx/Nkx2.5 kinase is a catalytic subunit of casein kinase II (CKII) that phosphorylates the serine residue between the first and second helix of the homeodomain. This CKII site is phosphorylated in vivo. CKII-dependent phosphorylation of the home... | SIGNOR-250924 |
P31751 | P35222 | 1 | phosphorylation | up-regulates | 0.57 | Phosphorylation of beta-catenin by akt promotes beta-catenin transcriptional activitywe have demonstrated that akt phosphorylates beta-catenin at ser552 in vitro and in vivo. | SIGNOR-152958 |
P08754 | O95622 | 2 | binding | down-regulates activity | 0.519 | Types V and VI adenylyl cyclase are most sensitive to inhibition by Gnai1, Gnai2, and Gnai3 | SIGNOR-278076 |
Q96Q42 | P20339 | 2 | binding | up-regulates activity | 0.735 | ALS2 activates Rab5 on macropinosomes. Rab5 is activated and concurrently recruited to macropinosomes during ruffle closure. ALS2 depletion abolishes transient Rab5 activation on macropinosomes, while ALS2 is recruited to macropinosomes simultaneously with Rab5 activation. Thus, we conclude ALS2 activates Rab5 on macro... | SIGNOR-277776 |
P51003 | Q6UN15 | 2 | binding | up-regulates | 0.791 | Recombinant hfip1 is sufficient to stimulate the in vitro polyadenylation activity of pap in a u-rich element-dependent manner. hfip1, cpsf160 and pap form a ternary complex in vitro, suggesting that hfip1 and cpsf160 act together in poly(a) site recognition and in cooperative recruitment of pap to the rna. | SIGNOR-121700 |
P61586 | P85298 | 0 | gtpase-activating protein | down-regulates activity | 0.427 | We therefore developed a screening-compatible live-cell imaging assay, using FRET-based biosensors for the prototype GTPases RHOA, RAC1 and CDC4215,19,20 (Extended Data Fig. 2 and Supplementary Note 1)|We found catalytic activities for 45/75 RhoGEFs and 48/63 RhoGAPs| Our data thus not only reveal extensive promiscuity... | SIGNOR-260463 |
Q99708 | Q504Q3 | 0 | deubiquitination | up-regulates activity | 0.2 | Here, we identify that USP52 directly interacts with and deubiquitinates CtIP, thereby promoting DNA end resection and HR. Mechanistically, USP52 removes the ubiquitination of CtIP to facilitate the phosphorylation and activation of CtIP at Thr-847. In addition, USP52 is phosphorylated by ATM at Ser-1003 after DNA dama... | SIGNOR-273509 |
P50148 | Q01726 | 2 | binding | up-regulates activity | 0.345 | Here we systematically quantified ligand-induced interactions between 148 GPCRs and all 11 unique G alpha subunit C-termini. For each receptor, we probed chimeric G alpha subunit activation via a transforming growth factor-alpha (TGF alpha) shedding response in HEK293 cells lacking endogenous Gq/11- and G12/13- signali... | SIGNOR-256956 |
P10912 | P17706 | 0 | dephosphorylation | down-regulates activity | 0.295 | PTPH1 only bound Tyr534, whereas PTP1B and TC-PTP bound multiple phosphopeptides. Earlier work suggests that Tyr332, Tyr487, Tyr534, Tyr566, and Tyr627 are all phosphorylated after GH stimulation (21). Apart from Tyr627, all of these also appear good PTP substrates | SIGNOR-248394 |
Q09472 | Q05655 | 0 | phosphorylation | down-regulates | 0.366 | Inhibition of histone acetyltransferase function of p300 by pkcdeltawe found that pkcdelta but not classical pkc, specifically phosphorylates p300 at serine 89 in vitro and in vivo. This phosphorylation causes inhibition of p300 intrinsic hat activity. | SIGNOR-94263 |
Q92878 | P38398 | 2 | binding | up-regulates | 0.789 | Brca1 interacts in vitro and in vivo with hrad50. Brca1 is important for the cellular responses to dna damage that are mediated by the hrad50-hmre11-p95 complex. | SIGNOR-69701 |
O60603 | Q86XR7 | 2 | binding | up-regulates activity | 0.429 | To initiate the innate immune response, Toll-like receptors (TLRs) associate with cytoplasmic adaptor proteins through TIR (Toll/interleukin-1 receptor) domain interactions. The four principal signaling adaptor proteins include MyD88, MAL, TRIF and TRAM, and the fifth protein SARM, involved in negative regulation of TL... | SIGNOR-266747 |
Q92843 | Q07812 | 2 | binding | down-regulates | 0.478 | Bcl-w may protect largely via its ability to associate with bax because it could efficiently protect xem from tbid and bid, bad, hrk, and bmf bh3 peptides | SIGNOR-154518 |
P52803 | P29317 | 2 | binding | up-regulates | 0.922 | Members of the epha subfamily of receptor tyrosine kinases and their ephrin-a ligands have been implicated in the guidance of retinal axons along the anterior-posterior axis of the chick optic tectum. | SIGNOR-52467 |
Q8N695 | P08047 | 0 | transcriptional regulation | up-regulates quantity by expression | 0.2 | Luciferase reporter assays of deletion mutants of SLC5A8 promoter demonstrated that a 295-bp region is essential for the basal promoter activity of the SLC5A8 gene. Further analysis indicated that the CCAAT boxes and GC boxes were involved in positive regulation of SLC5A8 promoter. Overexpression of two transcription f... | SIGNOR-254059 |
Q9UBE8 | Q9UJU2 | 1 | phosphorylation | down-regulates | 0.76 | Regulation of lymphoid enhancer factor 1/t-cell factor by mitogen-activated protein kinase-related nemo-like kinase-dependent phosphorylation in wnt/beta-catenin signaling.Nlk phosphorylates lef-1/tcf on two serine/threonine residues located in its central region. Mutation of both residues to alanine enhanced lef-1 tra... | SIGNOR-97812 |
P35568 | P42345 | 0 | phosphorylation | down-regulates activity | 0.766 | Mtor induced the serine phosphorylation of irs-1 (ser-636/639), and such phosphorylation was inhibited by rapamycin. These results suggest that tnf impairs insulin signaling through irs-1 by activation of a pi 3-kinase/akt/mtor pathway, which is antagonized by pten | SIGNOR-106590 |
P06241 | O75553 | 1 | phosphorylation | down-regulates activity | 0.614 | Tyrosine phosphorylation of Dab1 by Fyn inhibits its interaction with APP, while increasing its interaction with Fyn. | SIGNOR-278476 |
Q15797 | P12755 | 2 | binding | down-regulates | 0.699 | Ski also represses bmp signaling through interactions with smad4 and bmp-specific r-smads, smad1 or smad5. | SIGNOR-195630 |
P12931 | P18206 | 1 | phosphorylation | down-regulates activity | 0.76 | The phosphorylation of vinculin on tyrosine residues 100 and 1065, mediated by SRC kinases, affects cell spreadingWhen phosphorylated, the vinculin tail exhibited significantly less binding to the vinculin head domain than the unphosphorylated tail. | SIGNOR-247424 |
Q16539 | O95644 | 1 | phosphorylation | down-regulates | 0.622 | We show that jnk, erk, and p38 physically associate with the nfatc n-terminal regulatory domain and can directly phosphorylate functionally important residues involved in regulating nfatc subcellular localization, namely ser(172) and the conserved nfatc ser-pro repeats. | SIGNOR-74560 |
P31749 | Q96EB6 | 0 | deacetylation | up-regulates activity | 0.6 | We show that Akt and PDK1 are acetylated at lysine residues in their pleckstrin homology domains, which mediate PIP(3) binding. Acetylation blocked binding of Akt and PDK1 to PIP(3), thereby preventing membrane localization and phosphorylation of Akt. Deacetylation by SIRT1 enhanced binding of Akt and PDK1 to PIP(3) an... | SIGNOR-252445 |
P07550 | Q9H6Z9 | 0 | 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 ubiquityla... | SIGNOR-262007 |
P05231 | P08887 | 2 | binding | up-regulates | 0.918 | We show that the augmentation of the il6 signal by recombinant il6 receptors (ril6r) delivery allows the functional recovery of phagocytes in a peritonitis mouse model. | SIGNOR-137236 |
P99999 | Q9Y243 | 0 | phosphorylation | down-regulates activity | 0.265 | Finally, we propose that pro-survival kinase Akt (protein kinase B) is a likely mediator of the S47 phosphorylation of Cytc in the brain. | SIGNOR-277235 |
Q9H6Y7 | P51965 | 2 | binding | up-regulates activity | 0.537 | Here, we present evidences indicating that RING105, a novel conserved RING-finger protein with a PA (protease-associated) domain and a PEST sequence, is a ubiquitin ligase for TSSC5 that can function in concert with the ubiquitin-conjugating enzyme UbcH6. The polyubiquitin target site on TSSC5 was mapped to a region i... | SIGNOR-271552 |
P18510 | P14778 | 2 | binding | down-regulates activity | 0.897 | Homozygous truncating mutations result in lack of secreted interleukin-1–receptor antagonist protein, which inhibits the proinflammatory cytokines interleukin-1α and interleukin-1β | SIGNOR-262302 |
P02452 | Q8NBJ5 | 0 | glycosylation | up-regulates activity | 0.41 | Recombinant GLT25D1 and GLT25D2 enzymes showed a strong galactosyltransferase activity toward various types of collagen and toward the serum mannose-binding lectin MBL, which contains a collagen domain. Amino acid analysis of the products of GLT25D1 and GLT25D2 reactions confirmed the transfer of galactose to hydroxyly... | SIGNOR-261152 |
Q9H461 | P34925 | 2 | binding | up-regulates | 0.711 | Interaction between ryk and fz has been reported, suggesting that the two proteins may form a multi-receptor complex signalling through the canonical pathway | SIGNOR-150010 |
Q5TZA2 | Q68D86 | 2 | binding | up-regulates activity | 0.2 | CCDC102B is recruited to the centrosome by C-Nap1 (also known as CEP250) and interacts with the centrosome linker components rootletin and LRRC45. CCDC102B decorates and facilitates the formation of rootletin filaments. Furthermore, CCDC102B is phosphorylated by Nek2A (an isoform encoded by NEK2) and is disassociated f... | SIGNOR-275628 |
P48163 | P24752 | 0 | acetylation | up-regulates activity | 0.249 | PGAM5-mediated dephosphorylation of malic enzyme 1 (ME1) at S336 allows increased ACAT1-mediated K337 acetylation, leading to ME1 dimerization and activation, both of which are reversed by NEK1 kinase-mediated S336 phosphorylation. SIRT6 deacetylase antagonizes ACAT1 function in a manner that involves mutually exclusiv... | SIGNOR-275571 |
P07355 | Q5T6F2 | 0 | ubiquitination | down-regulates quantity | 0.341 | UBAP2 formed a complex with Annexin A2 and promoted the degradation of Annexin A2 protein by ubiquitination | SIGNOR-261314 |
P08047 | P67775 | 0 | dephosphorylation | up-regulates activity | 0.264 | These results indicate that the signals from TCDD or OP caused PP2A-mediated dephosphorylation of Sp1 at Ser-59 and induced CYP1A1 transcription | SIGNOR-248223 |
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