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 |
|---|---|---|---|---|---|---|---|
P09619 | P12931 | 1 | phosphorylation | up-regulates activity | 0.604 | The increased Src activity is mainly due to the phosphorylation of Tyr-419, rather than the dephosphorylation of Tyr-530 of Src protein. PDGFR, not FAK or EGFR, appears to be the upstream protein tyrosine kinase responsible for the detachment-induced Src activation in the lung tumor cells. | SIGNOR-247979 |
Q8N3Y1 | P35568 | 2 | binding | down-regulates quantity by destabilization | 0.46 | Defective IRS-1 degradation was due to attenuated expression and phosphorylation of the ubiquitin ligase substrate-targeting subunit, Fbw8. mTORC2 stabilizes Fbw8 by phosphorylation at Ser86, allowing the insulin-induced translocation of Fbw8 to the cytosol where it mediates IRS-1 degradation. | SIGNOR-271939 |
Q99705 | P63096 | 2 | binding | up-regulates activity | 0.437 | 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-257034 |
Q14511 | P30530 | 0 | phosphorylation | up-regulates activity | 0.2 | Mechanistically, AXL phosphorylates NEDD9, leading to its binding to CRKII which in turn associates with and orchestrates the phosphorylation of the pseudo-kinase PEAK1.|These results reveal NEDD9 as a specific AXL substrate.We next validated whether AXL promotes canonical NEDD9 signaling. | SIGNOR-278905 |
O43561 | P27361 | 0 | phosphorylation | down-regulates | 0.304 | Lat, an adapter protein essential for t-cell signaling, is phosphorylated at its thr 155 by erk in response to t-cell receptor stimulation. Thr 155 phosphorylation reduces the ability of lat to recruit plcgamma1 and slp76, leading to attenuation of subsequent downstream events such as [ca2+]i mobilization and activation of the erk pathway. | SIGNOR-125770 |
Q9Y4K3 | P51812 | 0 | phosphorylation | up-regulates activity | 0.272 | These results demonstrate that TRAF6 K63 ubiquitination might be regulated by an RSK2 mediated phosphorylation dependent mechanism and phosphorylation of TRAF6 at Ser46, 47 and 48 enhances its ubiquitin mediated inflammation signaling. | SIGNOR-278302 |
P52292 | Q09472 | 0 | acetylation | up-regulates | 0.357 | Ampk triggered the acetylation of importin alpha1 on lys(22), a process dependent on the acetylase activity of p300 | SIGNOR-128625 |
P01106 | P45984 | 0 | phosphorylation | up-regulates | 0.359 | The jnk pathway is selectively involved in the c-myc-mediated apoptosis and that the apoptotic function of c-myc is directly regulated by jnk pathway through phosphorylation at ser-62 and ser-71. | SIGNOR-72108 |
P10398 | Q02750 | 1 | phosphorylation | up-regulates | 0.74 | Our data demonstrated that a-raf is, indeed, a mek1 activator and may play a role in growth factor signaling|The immunoprecipitates were assayed for GST-MEK1 activation. D, activation of MEK1 by A-Raf requires the presence of serine residue 218 and 222. | SIGNOR-235944 |
O15350 | P24941 | 0 | phosphorylation | down-regulates activity | 0.575 | Cyclin-dependent kinases phosphorylate p73 at threonine 86 in a cell cycle-dependent manner and negatively regulate p73.Furthermore, cyclin a/cdk1/2, cyclin b/cdk1/2, and cyclin e/cdk2 complexes can phosphorylate multiple p73 isoforms in vitro at threonine 86. | SIGNOR-99746 |
Q9Y618 | P37231 | 1 | transcriptional regulation | down-regulates quantity by repression | 0.745 | In differentiated adipocyte cell lines, SIRT1 inhibits adipogenesis and enhances fat mobilization through lipolysis by suppressing the activity of PPARγ. SIRT1 achieves this by promoting the assembly of a corepressor complex, involving NCoR1 and SMRT, on the promoters of PPARγ target genes to repress their transcription. | SIGNOR-253508 |
O15528 | O95243 | 0 | transcriptional regulation | up-regulates quantity by expression | 0.377 | Phosphorylation of MBD4 promotes 5-meC glycosylase activity Further evidence emerged to support the involvement of MBD4 in active demethylation. Protein-kinase C phosphorylation of MBD4 at two specific serine residues (165 and 262) following parathyroid hormone stimulation was shown to promote demethylation within the CYP27B1 gene promoter [12] | SIGNOR-275682 |
P17947 | P23769 | 2 | binding | down-regulates activity | 0.577 | Here we demonstrate that a region of the PU.1 Ets domain (the winged helix–turn–helix wing) interacts with the conserved carboxyl-terminal zinc finger of GATA-1 and GATA-2 and that GATA proteins inhibit PU.1 transactivation of critical myeloid target genes. | SIGNOR-256071 |
P29350 | P63261 | 1 | dephosphorylation | down-regulates | 0.2 | Our data suggest that shp-1 plays a pivotal role in reorganization of cytoskeletal architecture inducing actin dephosphorylation. These results clearly demonstrate the direct interaction of shp-1 with actin | SIGNOR-99565 |
P15172 | Q8NG27 | 1 | transcriptional regulation | up-regulates quantity | 0.2 | ... chromatin immunoprecipitation (ChIP) analysis showed MYOD binds to a site upstream the Pja1 promoter preferentially in C2C12 cells induced to differentiate (Fig. 2c). In addition, over-expression of MyoD in human fibroblasts is sufficient to up-regulate Pja1 expression | SIGNOR-255718 |
P10589 | P24468 | 2 | binding | up-regulates | 0.257 | Arp-1/rxr, coup-tfi/rxr, and arp-1/coup-tfi heterodimers bound the fp330-3' site. | SIGNOR-79443 |
Q6P2H3 | P53350 | 0 | phosphorylation | up-regulates activity | 0.248 | In summary, our results identify Cep85 as a platform to directly relay the activities of Plk1 and Mst2 to Nek2A activation at centrosomes through phospho-Nek2A-assistant Cep85 phosphorylation by Plk1 at the onset of mitosis.|Plk1 Heavily Phosphorylates the Nek2A-Binding Domain in Cep85 at Centrosomes in Late G2. | SIGNOR-278367 |
Q99466 | Q00987 | 0 | ubiquitination | down-regulates | 0.37 | We demonstrate that the intracellular domain of notch 4 is targeted for ubiquitylation and hence degradation by the ubiquitin ligase mdm2. | SIGNOR-172826 |
O43451 | Q7Z570 | 0 | transcriptional regulation | down-regulates quantity by repression | 0.2 | ZNF804A has been implicated in susceptibility to schizophrenia by several genome-wide association studies (GWAS), follow-up association studies and meta-analyses. ZNF804A was identified as a schizophrenia-associated gene by GWAS and was predicted to play a role in DNA binding and transcription To identify the genes that are affected by ZNF804A, we manipulated the expression of the ZNF804A protein in HEK293 human embryonic kidney cell lines and performed a cDNA microarray analysis followed by qPCR. We found that ZNF804A-overexpression up-regulated four genes (ANKRD1, INHBE, PIK3AP1, and DDIT3) and down-regulated three genes (CLIC2, MGAM, and BIRC3). | SIGNOR-269466 |
Q00403 | Q12947 | 2 | binding | up-regulates activity | 0.491 | The human forkhead protein FREAC-2 contains two functionally redundant activation domains and interacts with TBP and TFIIB. FREAC-2 dependent activation of transcription by TFIIB. | SIGNOR-220317 |
Q13093 | Q9Y4A8 | 0 | transcriptional regulation | up-regulates quantity by expression | 0.363 | Moreover, we demonstrated that nuclear factor erythroid 2-related factor 3 (Nrf3) regulates Pla2g7 gene expression through direct binding to the promoter regions of Pla2g7 gene. | SIGNOR-268979 |
P24941 | P12272 | 1 | phosphorylation | down-regulates | 0.372 | Phosphorylation at the cyclin-dependent kinases site (thr85) of parathyroid hormone-related protein negatively regulates its nuclear localization | SIGNOR-68548 |
Q5T0W9 | P48730 | 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 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-273766 |
P35222 | P16591 | 0 | phosphorylation | down-regulates activity | 0.72 | Interaction of beta-catenin with alpha-catenin is regulated by the phosphorylation of beta-catenin Tyr-142. This residue can be phosphorylated in vitro by Fer or Fyn tyrosine kinases. Transfection of these kinases to epithelial cells disrupted the association between both catenins. | SIGNOR-251131 |
Q15466 | P03372 | 2 | binding | down-regulates | 0.649 | Our results identify shp as an inhibitor of 4-oht agonist activity in rl95-2 human endometrial carcinoma cells that express endogenous er?. We conclude that shp does not decrease er expression, but rather it is the direct interaction of shp with er that inhibits er transcriptional activity. | SIGNOR-115033 |
Q14934 | Q16539 | 0 | phosphorylation | down-regulates activity | 0.402 | P38 MAP kinase phosphorylates Ser168 and Ser170 of NFATc4. Mutational replacement of Ser168,170 with Ala promotes NFATc4 nuclear localization and increases NFATc4-mediated transcription activity. | SIGNOR-250107 |
Q96GD4 | P42575 | 1 | phosphorylation | up-regulates activity | 0.244 | Furthermore, in vitro phosphorylation using GST-Casp2 363-423 WT or S384A confirmed that S384 of caspase-2 is phosphorylated by AURKB. | SIGNOR-279496 |
P24863 | P46531 | 1 | phosphorylation | down-regulates | 0.48 | Purified recombinant cycc:cdk8 phosphorylates the notch icd within the tad and pest domains, and expression of cycc:cdk8 strongly enhances notch icd hyperphosphorylation and pest-dependent degradation by the fbw7/sel10 ubiquitin ligase in vivo. | SIGNOR-130592 |
Q9NRC8 | Q5TEC6 | 1 | deacetylation | up-regulates activity | 0.2 | Besides confirming the previously reported histone H3K18 deacylation activity, our results revealed that SIRT7 has an astonishingly high activity to catalyze deacylation of H3K36 and is also catalytically active to deacylate H3K37. | SIGNOR-275883 |
P15498 | P29350 | 0 | dephosphorylation | down-regulates activity | 0.576 | SHP-1 dephosphorylates and inactivates the guanine exchange factor Vav1. | SIGNOR-277171 |
O95665 | P30990 | 2 | binding | down-regulates | 0.898 | Neurotensin binding to recombinant neurotensin nt2 receptor expressed in cho cells does not elicit a biological response as determined by second messenger measurements. | SIGNOR-62519 |
Q13315 | Q99801 | 1 | phosphorylation | down-regulates quantity by destabilization | 0.362 | ATM phosphorylates NKX3.1 on T166 and then T134, resulting in NKX3.1 ubiquitination and degradation resulting from an apparent regulatory interaction. | SIGNOR-276499 |
P14652 | P32243 | 1 | transcriptional regulation | up-regulates quantity by expression | 0.259 | Transactivation of the mouse OTX2 Luc constructs by the human HOXB1, HOXB2, and HOXB3 proteins. | Likewise, the construct pOTX2LucΔ−710 showed an 8-, 12-, and 6-fold increase in transcriptional activity if co-transfected with pSG-HOXB1, -HOXB2, and -HOXB3, respectively | SIGNOR-261634 |
P10636 | Q9P0L2 | 0 | phosphorylation | down-regulates activity | 0.429 | We have studied the relationship between the phosphorylation of tau by several kinases (MARK, PKA, MAPK, GSK3) and its assembly into PHFs. MARK and PKA phosphorylate several sites within the repeats (notably the KXGS motifs including Ser262, Ser324, and Ser356, plus Ser320). This type of phosphorylation strongly reduces tau's affinity for microtubules, and at the same time inhibits tau's assembly into PHFs. | SIGNOR-250173 |
P51617 | Q9NWZ3 | 0 | phosphorylation | up-regulates activity | 0.687 | In addition, IRAK-4 is able to phosphorylate IRAK-1, and overexpression of dominant-negative IRAK-4 is blocking the IL-1-induced activation and modification of IRAK-1, suggesting a role of IRAK-4 as a central element in the early signal transduction of Toll/IL-1 receptors, upstream of IRAK-1. | SIGNOR-117315 |
P63279 | P41161 | 1 | sumoylation | down-regulates | 0.266 | Here we show that erm interacts with the sumo-conjugating enzyme ubc9 and is modified by sumo. We further show that sumo modification of this ets transcription factor affects its ability to activate transcription. | SIGNOR-135850 |
P04899 | Q08828 | 2 | binding | down-regulates activity | 0.597 | Adenylate cyclase is regulated by stimulatory hormones through Gs(alpha s beta gamma) and inhibitory hormones through Gi(alpha i beta gamma) | SIGNOR-256499 |
O95837 | O43613 | 2 | binding | up-regulates activity | 0.435 | 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-257294 |
P45983 | P54259 | 1 | phosphorylation | down-regulates activity | 0.376 | Dentatorubral-pallidoluysian atrophy protein is phosphorylated by c-jun nh2-terminal kinase. serine 734 of the drpla protein is a phospho-acceptor site by jnk. The phosphorylation may be coupled to the activation of a protease. The molecular size of drpla protein detected in the rat brain with the specific phosphopeptide antibody was 150_kda, which was slightly smaller than that expected from the sequence and the results with the human protein. The phosphorylated forms of ha-tagged human drpla gradually disappeared after osmotic treatment, | SIGNOR-102398 |
P08047 | Q9BSI4 | 1 | transcriptional regulation | up-regulates quantity by expression | 0.2 | Transfection of a plasmid carrying the Sp1 transcription factor into Sp-deficient SL2 cells strongly activated TIN2 promoter-driven luciferase reporter expression. | SIGNOR-271698 |
P53350 | Q9Y2I6 | 1 | phosphorylation | down-regulates activity | 0.7 | Here, we identify a centrosomal plk1 substrate, termed nlp (ninein-like protein), whose properties suggest an important role in microtubule organization. Nlp interacts with two components of the gamma-tubulin ring complex and stimulates microtubule nucleation. Plk1 phosphorylates nlp and disrupts both its centrosome association and its gamma-tubulin interaction | SIGNOR-103356 |
P29590 | Q15796 | 2 | binding | up-regulates activity | 0.549 | Cytoplasmic pml physically interacts with smad2/3 and sara (smad anchor for receptor activation) and is required for association of smad2/3 with sara and for the accumulation of sara and tgf-beta receptor in the early endosome. | SIGNOR-128738 |
P43405 | P12318 | 1 | phosphorylation | up-regulates activity | 0.673 | To identify the FcgammaRII-phosphorylating protein tyrosine kinase (PTK), we used the combination of an in vitro and an in vivo approach. In an in vitro assay using recombinant cytoplasmic tails of the different FcgammaRII isoforms as well as tyrosine exchange mutants, we show that each of the BCR-associated PTKs (Lyn, Blk, Fyn, and Syk) shows different phosphorylation patterns with regard to the different FcgammaR isoforms and pointFyn and Blk definitely phosphorylate Y-282 in the ITAM of Fc_RIIa/c, whereas the non-ITAM tyrosine residue (Y-275) becomes phosphorylated by Syk, as the phosphorylation of double point mutants shows. In addi-tion to these tyrosine residues, Fyn, Blk, and Syk might phosphorylate the most C-terminal tyrosine residue (Y-298) because altering this tyrosine residue together with one of the tyrosine residues clearly shown to be phosphorylated by the respective PTK results in the abrogation of phosphorylation. | SIGNOR-247590 |
P15502 | O95967 | 2 | binding | up-regulates activity | 0.557 | Fibulin-4 directly binds LOX, and this interaction enhances fibulin-4 binding to tropoelastin, thus forming a ternary complex that may be critical for elastin cross-linking. | SIGNOR-252136 |
O75604 | P36897 | 1 | deubiquitination | up-regulates activity | 0.2 | Here, we report the role of USP2a in promoting metastasis by facilitating TGF-β-triggered signaling. USP2a interacts with TGFBR1 and TGFBR2 upon TGF-β stimulation and removes K33-linked polyubiquitin chains from Lys502 of TGFBR1, promoting the recruitment of SMAD2/3. Simultaneously, TGFBR2 phosphorylates Ser207/Ser225 of USP2a, leading to the disassociation of SMAD2/3 from TGFBR1. | SIGNOR-273605 |
Q07687 | P28360 | 2 | binding | down-regulates activity | 0.399 | We demonstrate that dimerization by Msx and Dlx proteins is mediated through their homeodomains and that the residues required for this interaction correspond to those necessary for DNA binding. Unlike most other known examples of homeoprotein interactions, association of Msx and Dlx proteins does not promote cooperative DNA binding; instead, dimerization and DNA binding are mutually exclusive activities. Msx proteins act as transcriptional repressors and Dlx proteins act as activators, while in combination, Msx and Dlx proteins counteract each other's transcriptional activities. | SIGNOR-240918 |
P12931 | P15311 | 1 | phosphorylation | up-regulates | 0.648 | Src phosphorylates ezrin at tyrosine 477 and induces a phosphospecific association between ezrin and a kelch-repeat protein family member | SIGNOR-132907 |
Q06710 | P07202 | 1 | transcriptional regulation | up-regulates quantity by expression | 0.399 | TSH regulates TPO expression through the cAMP pathway and acts with thyroid-specific transcription factors such as TTF-1, TTF-2 and Pax-8. | SIGNOR-267277 |
Q15386 | O75155 | 1 | ubiquitination | down-regulates quantity by destabilization | 0.39 | We show that KIAA10 indeed associates with 26 S proteasomes in mammalian cells but that this interaction is likely to depend on contacts with a subunit(s) besides S2/Rpn1. Most importantly, we provide strong evidence that TIP120B (TBP-interacting protein 120B (22)) is a specific substrate that is targeted for degradation in skeletal muscle through KIAA10-catalyzed polyubiquitination. | SIGNOR-271454 |
P10586 | P53355 | 1 | dephosphorylation | up-regulates | 0.2 | Lar tyrosine phosphatase dephosphorylates dapk at py491/492 to stimulate the catalytic, proapoptotic, and antiadhesion/antimigration activities of dapk | SIGNOR-157706 |
O75896 | P46934 | 0 | ubiquitination | down-regulates quantity by destabilization | 0.2 | NEDD4 Degrades TUSC2 to Promote Glioblastoma Progression.|NEDD4 E3 ubiquitin ligase polyubiquitinates TUSC2 at residue K71, and the TUSC2-K71R mutant is resistant to NEDD4-mediated proteasomal degradation. | SIGNOR-278638 |
Q9UPW6 | Q9H3D4 | 2 | binding | down-regulates activity | 0.372 | SATB2 attenuates p63-mediated gene expression of perp (p53 apoptosis effector related to PMP-22), a critical downstream target gene during development, and specifically decreases p63 perp promoter binding. | SIGNOR-255149 |
Q06330 | P38936 | 1 | transcriptional regulation | up-regulates quantity by expression | 0.307 | Induction of the p21WAF1/Cip1 gene by Notch 1 activation in differentiating keratinocytes is associated with direct targeting of the RBP-J_ protein to the p21 promoter. | SIGNOR-252032 |
Q9UNN4 | P68400 | 0 | phosphorylation | up-regulates activity | 0.424 | ALF was able to stabilize the binding of TBP to DNA, but it could not stabilize TBP mutants A184E, N189E, E191R, and R205E nor could it facilitate binding of the TBP-like factor TRF2/TLF to a consensus TATA element. However, phosphorylation of ALF with casein kinase II resulted in the partial restoration of complex formation using mutant TBPs. | Because the residues involved (Ser-280, Ser-281, Ser-316, and Ser-321) are conserved in ALF (Ser-356, Ser-357, Ser-418, and Ser-423), we tested whether its activity might also be affected by this modification. We first showed that ALF and TFIIAα/β polypeptides incubated with casein kinase II and [γ-32P]ATP could be labeled. | SIGNOR-250873 |
Q6ZUJ8 | P42338 | 2 | binding | up-regulates | 0.418 | This accumulation of tyrosine-phosphorylated bcap at the membrane with its associated pi3k would then allow for the catalysis of ptd ins p2 to ptd ins p3 and downstream pi3k-dependent signals. Therefore, bcap is an essential activator of the pi3k pathway downstream of tlr signaling, providing a brake to limit potentially pathogenic excessive tlr responses. | SIGNOR-191667 |
P78527 | Q9UBK2 | 1 | phosphorylation | down-regulates quantity by destabilization | 0.2 | Mechanistically, PGC1α was phosphorylated at serine (S) 636 by DNA-dependent protein kinase in response to irradiation. Phosphorylation at S636 promoted the degradation of PGC1α by facilitating its binding to the E3 ligase RNF34. | SIGNOR-277911 |
Q15418 | P17676 | 1 | phosphorylation | up-regulates activity | 0.683 | 13 The data presented support previous findings that C/EBPbeta can be a molecular target of RSK1, 16 but provide the first indication that RSK1 can phosphorylate and activate C/EBPbeta to mediate the IL-6 signalling events in cholangiocarcinoma.|As mentioned above, RSK1 has been shown to activate C/EBPbeta in hepatic stellate cells in an experimental model of liver fibrosis. | SIGNOR-280112 |
P01241 | P16471 | 2 | binding | up-regulates | 0.777 | Hprl does not bind to the hgh receptor, but hgh binds to both the hghr and hprlr, and mutagenesis studies have shown that the receptor-binding sites on hgh overlap. | SIGNOR-35575 |
P11511 | P12931 | 0 | phosphorylation | up-regulates | 0.35 | Phosphorylation of the 361-tyrosine residue is crucial in the up-regulation of aromatase activity. c-src protein directly phosphorylates aromatase on tyrosine 361. | SIGNOR-186284 |
P18031 | Q9H1D0 | 1 | dephosphorylation | down-regulates activity | 0.631 | In HEK293 cells, transfected with the Ca2+ channel protein TRPV6, Ca2+ influx is increased and TRPV6 is tyrosine phosphorylated following addition of the tyrosine phosphatase inhibitor|PTP1B interacts with the N-terminal domain of TRPV6 within a region of amino acids 1-191 as shown by co-immunoprecipitation, bimolecular fluorescence complementation and the yeast 2-hybrid system. Point mutation of both tyrosines 161 and 162 in the TRPV6 protein abolishes the DMHV-effect on Ca2+ influx and tyrosine phosphorylation by Src. Single mutations of Y161 or Y162 shows that each of both tyrosines alone is sufficient for the DMHV-effect. We conclude that phosphorylation/dephosphorylation of tyrosines in position 161 and 162 is essential for regulation of Ca2+ influx through TRPV6 Ca2+ channels in HEK293 cells. | SIGNOR-248433 |
Q8N2Q7 | P78352 | 1 | relocalization | up-regulates activity | 0.776 | Like NRXNs, NLGNs bind to intracellular PDZ-domain proteins, but in contrast to NRXNs, NLGNs bind to class I PDZ domains such as those contained in PSD95, a postsynaptic MAGUK protein65. PSD95 and its homologues are centrally involved in recruiting glutamate receptors at postsynaptic sites66. Similarly to CASK, PSD95 binds to intracellular adaptor proteins, and especially to GKAP (a protein that binds to the guanylate-kinase domain of PSD95), which, in turn, binds to SHANK proteins (Fig. 1b). A possible role of these interactions is to recruit postsynaptic adaptor proteins to the site of synaptic junctions. | SIGNOR-264191 |
P29275 | P50148 | 2 | binding | up-regulates activity | 0.4 | 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-257365 |
Q99814 | Q9Y2N7 | 0 | transcriptional regulation | down-regulates quantity by repression | 0.53 | None of the long HIF-3α variants was capable of efficient induction of an HRE reporter in overexpression experiments, but instead inhibited the transcriptional activation of the reporter by HIF-1 and HIF-2. | SIGNOR-261616 |
P29353 | Q02156 | 0 | phosphorylation | up-regulates activity | 0.2 | Among them, Ser(29) in p52(Shc) (equivalent to Ser(138) in p66(Shc)) was phosphorylated only after TPA stimulation. Phosphorylation of this site together with the intact phosphotyrosine-binding domain was essential for ShcA binding to the protein-tyrosine phosphatase PTP-PEST. TPA-induced ShcA phosphorylation at this site (and hence, its association with PTP-PEST) was inhibited by a protein kinase C-specific inhibitor and was induced by overexpression of constitutively active mutants of protein kinase Calpha, -epsilon, and -delta isoforms. | SIGNOR-263048 |
P34995 | Q03113 | 2 | binding | up-regulates activity | 0.263 | 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-257278 |
P51532 | Q8TAQ2 | 2 | binding | up-regulates | 0.939 | The remodeling activity of brg1 and hbrm is stimulated by baf170/baf155 and is further stimulated when ini1 is added. | SIGNOR-65444 |
P20749 | P49840 | 0 | phosphorylation | down-regulates quantity by destabilization | 0.392 | In this report, we show that BCL-3 is a substrate for the protein kinase GSK3 and that GSK3-mediated BCL-3 phosphorylation, which is inhibited by Akt activation, targets its degradation through the proteasome pathway. | SIGNOR-276011 |
P68400 | Q01892 | 1 | phosphorylation | down-regulates | 0.429 | Serine residues 37 in the transactivation domain and 129, 144 and 146 in the pest domain of spi-b are phosphorylated by ckii in vitro. The ckii phosphorylation sites mapped in vitro are phosphorylated in vivo. Mutations of the ckii phosphorylation sites increase the ability of spi-b to transactivate. Spi-b phosphorylation by ckii reduces its stability | SIGNOR-73891 |
O14974 | O75116 | 0 | phosphorylation | down-regulates activity | 0.785 | Rho kinase is known to control smooth muscle contractility by phosphorylating the 110 kDa myosin-targetting subunit (MYPT1) of the myosin-associated form of protein phosphatase 1 (PP1M). Phosphorylation of MYPT1 at Thr695 has previously been reported to inhibit the catalytic activity of PP1. Here, we show that the phosphorylation of Thr850 by Rho kinase dissociates PP1M from myosin, providing a second mechanism by which myosin phosphatase activity is inhibited. | SIGNOR-249164 |
Q9ULC4 | O43583 | 2 | binding | up-regulates activity | 0.746 | The MCT-1 protein modifies mRNA translational profiles through its interaction with DENR/DRP, a protein containing an SUI1 domain involved in recognition of the translation initiation codon. | SIGNOR-269674 |
Q16539 | Q9H3D4 | 1 | phosphorylation | down-regulates quantity by destabilization | 0.307 | P38α phosphorylates and destabilizes p63. | SIGNOR-277414 |
P49840 | Q96RR4 | 1 | phosphorylation | down-regulates | 0.269 | Cdk5 and gsk3 phosphorylate ser-129, ser-133, and ser-137. Mutation of ser-129, ser-133, and ser-137 increases autonomous activity with little change in ca2 /cam-dependent activity. | SIGNOR-198122 |
P46937 | Q05513 | 0 | phosphorylation | down-regulates quantity by destabilization | 0.277 | Yap and β-catenin are direct substrates of PKCζ.We show here that PKCζ suppresses intestinal stem cell function by promoting the downregulation of β-catenin and Yap through direct phosphorylation.Consistent with MS/MS analysis, mutation to alanine of these two sites completely abolished Yap phosphorylation by PKCζ. Interestingly, S109 and T110 sites were highly conserved among species (Figure S3B), which suggested an important role in Yap regulation. | SIGNOR-276877 |
Q96J02 | Q15796 | 1 | ubiquitination | up-regulates | 0.453 | Itch promotes ubiquitination of smad2 and augments smad2 phosphorylation that requires an intact ligase activity of itch. Moreover, itch facilitates complex formation between tgf-beta receptor and smad2 and enhances tgf-beta-induced transcription. | SIGNOR-128647 |
Q9Y5J3 | P46531 | 0 | transcriptional regulation | up-regulates quantity by expression | 0.774 | These data establish that HERP2 is a novel primary target gene of Notch that, together with HES, may effect diverse biological activities of Notch | SIGNOR-235397 |
P08754 | P46663 | 2 | binding | up-regulates activity | 0.435 | 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-257149 |
P04271 | P09630 | 0 | transcriptional regulation | up-regulates quantity by expression | 0.2 | HOXC6 and HOXC11 increase transcription of S100beta gene in BrdU-induced in vitro differentiation of GOTO neuroblastoma cells into Schwannian cells. | SIGNOR-261646 |
P24941 | O15350 | 1 | phosphorylation | down-regulates activity | 0.575 | Cyclin-dependent kinases phosphorylate p73 at threonine 86 in a cell cycle-dependent manner and negatively regulate p73.Furthermore, cyclin a/cdk1/2, cyclin b/cdk1/2, and cyclin e/cdk2 complexes can phosphorylate multiple p73 isoforms in vitro at threonine 86. | SIGNOR-99746 |
P01100 | P49675 | 1 | transcriptional regulation | up-regulates quantity by expression | 0.259 | We found that both SF1 and LRH1 can transcriptionally cooperate with the AP-1 family members c-JUN and c-FOS, known to be associated with enhanced proliferation of endometrial carcinoma cells, to further enhance activation of the STAR, HSD3B2, and CYP19A1 PII promoters. | SIGNOR-254878 |
P40337 | O96017 | 0 | phosphorylation | up-regulates | 0.455 | We demonstrated that checkpoint kinase-2 (chk2) binds to the beta-domain of pvhl and phosphorylates ser 111 on dna damage. Notably, this modification enhances pvhl-mediated transactivation of p53 by recruiting p300 and tip60 to the chromatin of p53 target gene | SIGNOR-177091 |
P42858 | Q00535 | 0 | phosphorylation | up-regulates | 0.447 | Huntingtin is an antiapoptotic proteinwe show here that huntingtin is phosphorylated by the cyclin-dependent kinase 5 (cdk5) at serines 1181 and 1201. Phosphorylation can be induced by dna damage in vitro and in vivo. The state of huntingtin phosphorylation is a crucial regulator of neuronal cell death. Absence of phosphorylation of huntingtin at serines 1181 and 1201 confers toxic properties to wild-type huntingtin in a p53-dependent manner in striatal neurons and accelerates neuronal death induced by dna damage. | SIGNOR-156840 |
O15294 | O43151 | 2 | binding | up-regulates | 0.443 | Tet2 and tet3 associate with the o_glcnac transferase ogt / tet2 and tet3 promote ogt_mediated glcnacylation | SIGNOR-200729 |
Q13233 | Q4V328 | 2 | binding | up-regulates activity | 0.312 | To examine whether GRASP‐1 interacts with MEKK1 and JNK1 in neurons, co‐immunoprecipitation experiments were performed with detergent‐solubilized extracts from cultured cortical neurons. Both antiJNK1 and anti‐MEKK1 antibodies immunoprecipitated GRASP‐1 from neuronal lysates. These results suggest that GRASP‐1 interacts with MEKK1 and JNK1 in neurons. | SIGNOR-260640 |
P84022 | P31749 | 2 | binding | down-regulates | 0.622 | Pkb inhibits smad3 by preventing its phosphorylation, binding to smad4 and nuclear translocation. [...] Regulation of smad3 by pkb occurs through a kinase-activity-independent mechanism, resulting in a decrease in smad3-mediated transcription and protection of cells against tgf-beta-induced apoptosis. | SIGNOR-123606 |
Q13627 | P61962 | 2 | binding | up-regulates activity | 0.71 | Two isoforms of DYRK, DYRK1A and DYRK1B, co-immunoprecipitate with HAN11 when coexpressed in COS cells indicating that the proteins interact in mammalian cells. HAN11 might target DYRKs to cytosolic locations for regulation of specific cellular functions. | SIGNOR-260630 |
P09471 | Q96G91 | 2 | 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-257261 |
Q15910 | P24941 | 0 | phosphorylation | up-regulates activity | 0.547 | Here, we demonstrate that the phosphorylation of EZH2 by cyclin-dependent kinases at Thr416 creates a docking site for the ForkHead-associated domain of NIPP1. | SIGNOR-255656 |
Q8IX07 | P15976 | 2 | binding | up-regulates activity | 0.798 | GATA-2 induces the expression of GATA-1, which first activates its cofactor FOG-1, and then downregulates GATA-2 cooperatively with FOG-1. | SIGNOR-256059 |
Q6ZVD8 | Q13043 | 1 | dephosphorylation | up-regulates activity | 0.2 | PHLPPs dephosphorylate Mst1 on the T387 inhibitory site, which activate Mst1 and its downstream effectors p38 and JNK to induce apoptosis. | SIGNOR-248730 |
P06239 | Q8IWV1 | 1 | phosphorylation | up-regulates activity | 0.399 | Upon stimulation via the B or T cell receptors, LAX is rapidly phosphorylated by Src and Syk family tyrosine kinases and interacts with Grb2, Gads, and p85. | SIGNOR-273528 |
P27540 | P04798 | 1 | transcriptional regulation | up-regulates quantity by expression | 0.646 | Kaempferol proved to be capable of inhibiting binding of agonist and agonist-induced formation of the AHR/ARNT DNA-binding complex and upregulation of the AHR target gene, CYP1A1. | SIGNOR-259910 |
Q12933 | Q99683 | 2 | binding | up-regulates activity | 0.737 | Traf2 is a strong activator of ask1 | SIGNOR-60747 |
Q13315 | O43684 | 1 | phosphorylation | up-regulates activity | 0.312 | Taken together, we highlight the functional significance of the crosstalk between the kinetochore-oriented signal and double-strand break repair pathways via ATM phosphorylation of Bub3 on Ser135. | SIGNOR-277582 |
Q9UD71 | P62136 | 2 | binding | down-regulates activity | 0.599 | DARPP-32 (dopamine and cyclic AMP-regulated phospho-protein, relative molecular mass 32,000) is converted into an inhibitor of protein phosphatase 1 when it is phosphorylated by protein kinase A (PKA) at threonine 34.‚ | SIGNOR-264957 |
P06241 | P52757 | 1 | phosphorylation | down-regulates | 0.2 | Ere we report that beta2-chimaerin is tyrosine-phosphorylated by src-family kinases (sfks) upon cell stimulation with epidermal growth factor (egf). these results suggest tyr-21 phosphorylation as a novel, sfk-dependent mechanism that negatively regulates beta2-chimaerin rac-gap activity. | SIGNOR-155709 |
Q9BZX2 | Q86U44 | 0 | post transcriptional regulation | up-regulates quantity by stabilization | 0.2 | Furthermore, the m6A modification regulated by METTL3 led to UCK2 increased messenger RNA (mRNA) stability in melanoma cancer. Functional and mechanistic experiments indicated that UCK2 enhanced the metastasis of melanoma cancer cells through the WNT/β-catenin pathway. | SIGNOR-275862 |
Q13153 | P35813 | 0 | dephosphorylation | down-regulates activity | 0.337 | Purified PP2Cα protein efficiently dephosphorylated PAK1 in vitro (Fig. 1, D and E). We previously assessed the time course of phospho-PAK1 dephosphorylation assessed using specific antibodies against either Ser(P)198/203 or Thr(P)422 sites in the PAK1 activation loop. | SIGNOR-248492 |
P55957 | P49674 | 0 | phosphorylation | up-regulates activity | 0.345 | Here we report that Bid is phosphorylated by casein kinase I (CKI) and casein kinase II (CKII). Inhibition of CKI and CKII accelerated Fas-mediated apoptosis and Bid cleavage, whereas hyperactivity of the kinases delayed apoptosis. | These results suggest that residues S61, S64, and to a much lesser extent T58 are sites of phosphorylation of Bid. | SIGNOR-250806 |
Q13253 | P36894 | 2 | binding | down-regulates activity | 0.611 | Noggin binds the domain that is re-quired for bmp-7 to interact with bmp type i and type ii receptors (PMID 22298955).Noggin Inhibits bmp by blocking the molecular interfaces of the binding epitopes for both type i and type ii receptors. | SIGNOR-219221 |
P32238 | P38405 | 2 | binding | up-regulates activity | 0.264 | Here we systematically quantified ligand-induced interactions between 148 GPCRs and all 11 unique G alpha subunit C-termini. For each receptor, we probed chimeric G alpha subunit activation via a transforming growth factor-alpha (TGF alpha) shedding response in HEK293 cells lacking endogenous Gq/11- and G12/13- 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-256906 |
Subsets and Splits
No community queries yet
The top public SQL queries from the community will appear here once available.