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 |
|---|---|---|---|---|---|---|---|
P52565 | P63000 | 1 | guanine nucleotide exchange factor | down-regulates activity | 0.811 | Here, we report the expression of plexin-B3 in glioma cells, which upon stimulation by its ligand Sema5A results in significant inhibition of cell migration and invasion. A search for the underlying mechanism revealed direct interaction of plexin-B3 with RhoGDP dissociation inhibitor α (RhoGDIα), a negative regulator o... | SIGNOR-268436 |
Q9BZE0 | Q9UMX1 | 0 | relocalization | down-regulates | 0.266 | Negative regulation of gli1 and gli2 activator function by suppressor of fused through multiple mechanisms.Together, these observations reveal that su(fu) regulates the activity of gli1 and gli2 through distinct cytoplasmic and nuclear mechanisms. | SIGNOR-142608 |
O15054 | Q15306 | 1 | transcriptional regulation | up-regulates quantity by expression | 0.422 | JMJD3 seems to function by controlling expression of the transcription factor IRF4, which in turn is required for M2 polarization of macrophages in vitro and in vivo. Although this pathway is strongly supported by genetic. | SIGNOR-249540 |
Q07817 | O14727 | 2 | binding | down-regulates activity | 0.842 | These experiments demonstrate that bcl-xl associates with caspase-9 and apaf-1, and show that bcl-xl inhibits the maturation of caspase-9 mediated by apaf-1. | SIGNOR-56399 |
P13807 | Q9Y463 | 0 | phosphorylation | down-regulates activity | 0.258 | DYRK Family Protein Kinases Phosphorylate and Inactivate Glycogen Synthase. both protein kinases phosphorylate site 3a but no other sites that affect glycogen synthase activity. | SIGNOR-260633 |
Q6WCQ1 | Q13464 | 0 | phosphorylation | down-regulates | 0.296 | Enhanced rho kinase activity induces endothelial barrier dysfunction by a contractile mechanism via inactivation of myosin phosphatase (mp).. | SIGNOR-157593 |
O75116 | Q99962 | 1 | phosphorylation | down-regulates | 0.439 | We identified the phosphorylation site of endophilin a1 at thr-14 endophilin t14d inhibited egf receptor internalization. Furthermore, phosphorylation of endophilin by rho-kinase inhibited the binding to cin85. | SIGNOR-140466 |
Q15915 | P08151 | 1 | relocalization | up-regulates | 0.377 | Co-expression of zic1 resulted in gli1 and gli3 proteins being translocated to the nucleus in varying levels | SIGNOR-105491 |
Q96P68 | P19086 | 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- signali... | SIGNOR-257310 |
Q9NPA3 | Q92748 | 2 | binding | down-regulates activity | 0.512 | In the current study, we have determined the crystal structure of mouse S14 to 2.65-Å resolution. The structure of S14 reveals a helical protein arranged as a symmetric dimer. Cultured cell experiments indicate that S14 can form heterodimers with MIG12, suggesting a mechanism through which S14 could modulate ACC activi... | SIGNOR-267113 |
Q9BZ95 | P01106 | 2 | binding | up-regulates quantity by stabilization | 0.2 | Indeed, dose-dependent TR-FRET and affinity pull-down assay confirmed the interaction of NSD3-s with MYC. Supporting functional significance of the interaction, co-expression of NSD3-s, but not the MYC-binding defective fragment of NSD3-s (1–347), stabilized MYC protein and increased MYC transcriptional activity as rev... | SIGNOR-259199 |
P01222 | Q92911 | 1 | transcriptional regulation | up-regulates quantity by expression | 0.38 | I– uptake is stimulated by TSH, the master hormone for thyroid gland regulation. TSH stimulation results, at least in part, from the cAMP-mediated increase in NIS biosynthesis. TSH not only stimulates NIS transcription and biosynthesis but is also required for modulating the NIS phosphorylation pattern, maintaining i... | SIGNOR-251995 |
Q99683 | Q9UER7 | 2 | phosphorylation | up-regulates | 0.841 | Our data demonstrated that ask1 controls the cytoplasmic localization of daxx (fig.1). our results indicate that daxx not only activates ask1 but also is a downstream target of ask1 and that accumulated daxx further activates ask1. Thus, the daxx-ask1 positive feedback loop amplifying jnk/p38 signaling plays an importa... | SIGNOR-188321 |
Q5S007 | P10636 | 1 | phosphorylation | down-regulates | 0.528 | Lrrk2 directly phosphorylates tubulin-associated tau, but not free tau;(iii) lrrk2 phosphorylates tau at thr181 as one of the target sites;. furthermore, we revealed that lrrk2-mediated phosphorylation of tau reduces its tubulin-binding ability. | SIGNOR-195756 |
Q9Y2K7 | Q99814 | 0 | transcriptional regulation | up-regulates quantity by expression | 0.2 | To this end, we confirm that KDM3A, KDM4B, KDM4C, KDM5B, KDM5C, and KDM62 are direct targets of HIF-1a while extent the list of known targets to KDM2A, KDM2B, KDM4D, KDM5A, and KDM6A. The results demonstrated that majority of the KDMs were similarly induced (KDM2A, KDM2B, KDM3A, KDM4B, KDM4C, KDM4D, KDM5A, KDM5B, KDM5C... | SIGNOR-271581 |
O60282 | P54257 | 2 | binding | up-regulates activity | 0.402 | HAP1 and GRIP1 are kinesin-1 adaptors that have been implicated individually in the transport of vesicular cargoes in the dendrites of neurons. We find that HAP1a and GRIP1 form a protein complex in the brain, and co-operate to activate the kinesin-1 subunit KIF5C in vitro | SIGNOR-264062 |
P50542 | Q13608 | 2 | binding | up-regulates activity | 0.569 | Pex1, Pex6, and Pex26 are involved in Pex5 export from peroxisomes., we found that Pex1 and Pex6 bind to Pex5 (Fig. (Fig.6). Therefore, it is conceivable that Pex1 and Pex6 pull out Pex5 from peroxisome membranes in an ATP-dependent manner. | SIGNOR-253619 |
Q96RD6 | Q15208 | 0 | 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 fact... | SIGNOR-263032 |
P51692 | P00533 | 0 | phosphorylation | up-regulates | 0.829 | Novel activation of stat5b in response to epidermal growth factor. novel activation of stat5b in response to epidermal growth factor. | SIGNOR-113393 |
Q9HAU4 | Q13873 | 1 | ubiquitination | down-regulates | 0.503 | Smurf1 and smurf2 are e3 ubiquitin ligases known to suppress tgf-beta signaling through degra-dation of smads and receptors for tgf-beta and bmps. | SIGNOR-193119 |
O14757 | Q9HAW4 | 2 | phosphorylation | up-regulates | 0.794 | We found that thr-916 on claspin is phosphorylated by chk1, suggesting that chk1 regulates claspin during checkpoint response. | SIGNOR-149411 |
Q9BXM7 | Q9UJA2 | 1 | phosphorylation | down-regulates quantity | 0.429 | In vitro kinase assays using recombinant proteins under various control conditions indicated that PINK1 directly phosphorylates CLS1 (XREF_FIG).|Similar to Fbxo15, knockdown of PINK1 kinase using shRNA increased CLS1 levels, whereas overexpression of PINK1 plasmid decreased CLS1 levels . | SIGNOR-280065 |
Q96TA2 | O60313 | 1 | cleavage | up-regulates activity | 0.455 | YME1L cleaves OPA1 at S2 and S3 site to transform into L-OPA1 to induce fusion when cells are faced with increased oxidative phosphorylation, whereas OMA1 cleaves OPA1 at an S1 site to transform into S-OPA1, resulting in the fragmented response to cellular stress, mitochondrial dysfunction, or deletion of YME1L | SIGNOR-274140 |
Q6PIY7 | P31749 | 0 | phosphorylation | down-regulates activity | 0.2 | We found that Gld2 activity is regulated by site-specific phosphorylation in its disordered N-terminal domain. We identified two phosphorylation sites (S62, S110) where phosphomimetic substitutions increased Gld2 activity and one site (S116) that markedly reduced activity. Using mass spectrometry, we confirmed that HEK... | SIGNOR-259405 |
P05067 | Q9Y5Z0 | 0 | cleavage | up-regulates activity | 0.544 | BACE2, a beta -secretase homolog, cleaves at the beta site and within the amyloid-beta region of the amyloid-beta precursor protein.|Figure 6 Preferred BACE1 and BACE2 cleavage sites. (A) Sequence of APP indicating α- and β-cleavage sites, BACE1- and BACE2-cleavage sites, and the location of mutations analyzed here. ... | SIGNOR-261773 |
P19634 | O00141 | 0 | phosphorylation | up-regulates activity | 0.304 | Phosphorylation of NHE1 Ser 703 by SGK1 is essential for the binding of 14-3-3 protein to NHE1 , ] which, in turn, is critical in the activation of this Na + / H + exchanger , ].|These data suggest that endothelial SGK1 activates NHE1 in response to MG treatment. | SIGNOR-280123 |
P38398 | Q7Z6Z7 | 0 | ubiquitination | down-regulates quantity by destabilization | 0.397 | Collectively, these data indicate that HUWE1 targets BRCA1, but not BARD1, for polyubiquitination and degradation.Because HUWE1 promotes BRCA1 ubiquitination and degradation, we wondered whether it might contribute to the reduced BRCA1 protein levels in sporadic breast cancer. | SIGNOR-278583 |
P23760 | P15056 | 0 | phosphorylation | up-regulates activity | 0.308 | BRAF activates PAX3 to control muscle precursor cell migration during forelimb muscle development.|We found that BRAF clearly induced phosphorylation of PAX3 at Ser205 in both cell types (XREF_FIG). | SIGNOR-278435 |
P45985 | P21333 | 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 |
P14867 | Q8TAB3 | 2 | binding | up-regulates quantity by stabilization | 0.364 | Here, we found that PCDH19 binds the alpha subunits of GABAAR and regulates its surface availability and currents in cultured hippocampal neurons. The PCDH19 gene (Xp22.1) encodes the cell-adhesion protein protocadherin-19 (PCDH19) and is responsible for a neurodevelopmental pathology characterized by female-limited ep... | SIGNOR-267217 |
P53350 | Q9UBW7 | 1 | phosphorylation | down-regulates quantity by destabilization | 0.376 | PLK1 and HOTAIR Accelerate Proteasomal Degradation of SUZ12 and ZNF198 during Hepatitis B Virus-Induced Liver Carcinogenesis|Similar analyses with ZNF198 identified two clusters of putative Plk1 phosphorylation sites in vitro. A cluster of serine residues at the N-terminus of ZNF198, S303, S305, and S309, and a cluster... | SIGNOR-275560 |
Q99466 | Q8IZL2 | 2 | binding | up-regulates | 0.86 | We show here identification of two new members of human mam family (human mastermind-2 (hmam-2) and human mastermind-3 (hmam-3)), which retain characteristics similar to human mastermind-1 (hmam-1) and drosophila mastermind. Both hmam-2 and hmam-3 stabilize and participate in the dna-binding complex rbp-j/cbf-1 protein... | SIGNOR-94279 |
Q96J84 | P06241 | 0 | phosphorylation | up-regulates activity | 0.2 | Here we have characterized Neph1, another SD component, as a novel substrate of SFK. Fyn interacts with and phosphorylates the cytoplasmic domain of Neph1 in vitro and in intact cells. Both tyrosine 637 and 638 of Neph1 are crucial for Neph1-Grb2 binding. | SIGNOR-262746 |
P20823 | O60656 | 1 | 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 |
Q96J92 | Q9UEW8 | 1 | phosphorylation | up-regulates activity | 0.507 | Vitari et al. (76) and Moriguchi et al. (52) demonstrated that WNK4 bound and phosphorylated PASK at Thr-233 and Ser-373 in mammalian cells.| this phosphorylation event activates PASK, which in turn phosphorylates and activates NKCC1 | SIGNOR-264641 |
Q9UQM7 | Q05397 | 1 | phosphorylation | up-regulates | 0.272 | Furthermore, activated camkii directly phosphorylated the recombinant cooh-terminal region of fak at a residue equivalent to ser-843. | SIGNOR-135631 |
Q14106 | P06493 | 0 | phosphorylation | up-regulates activity | 0.2 | Taken together, these observations strongly support the notion that several different CDK-cyclin complexes are involved in the phosphorylation of Tob2 at S254.A more detailed regulatory context of Tob2 phosphorylation at S254 is provided by our findings from mass-spec and in vitro kinase analyses that suggest connectio... | SIGNOR-273591 |
O00429 | Q05655 | 0 | phosphorylation | up-regulates | 0.2 | Drp1 was specifically phosphorylated in mitosis by cdk1/cyclin b on ser-585. Exogenous expression of unphosphorylated mutant drp1s585a led to reduced mitotic mitochondrial fragmentation. | SIGNOR-153148 |
P00533 | P35637 | 1 | phosphorylation | up-regulates activity | 0.259 | Thus, EGFR appears to mediate FUS nuclear translocation by phosphorylating Y6 and Y296 in FUS. | SIGNOR-279168 |
P62837 | Q9C035 | 2 | binding | up-regulates activity | 0.457 | Here, we show that TRIM5alpha functions as a RING-finger-type E3 ubiquitin ligase both in vitro and in vivo and ubiquitinates itself in cooperation with the E2 ubiquitin-conjugating enzyme UbcH5B. | SIGNOR-271670 |
Q9NZJ0 | Q86XK2 | 2 | binding | down-regulates | 0.544 | We determined that the f-box protein fbxo11 interacts with cdt2,a dcaf protein that controls cell-cycle progression, and recruits cdt2 to the scf(fbxo11)complex to promote its proteasomal degradation. | SIGNOR-192325 |
P16591 | P14923 | 1 | phosphorylation | up-regulates activity | 0.526 | The tyrosine kinase Fer, which modifies beta-catenin Tyr142, lessening its association with alpha-catenin, phosphorylates plakoglobin Tyr549 and exerts the contrary effect: it raises the binding of plakoglobin to alpha-catenin. Fer stimulation, through modification of Tyr549, causes diminished binding of plakoglobin to... | SIGNOR-251134 |
P59595 | P84022 | 2 | binding | up-regulates activity | 0.2 | In this study, we demonstrate that SARS-associated coronavirus (SARS-CoV) nucleocapsid (N) protein potentiates transforming growth factor-beta (TGF-beta)-induced expression of plasminogen activator inhibitor-1 but attenuates Smad3/Smad4-mediated apoptosis of human peripheral lung epithelial HPL1 cells. The promoting ef... | SIGNOR-260434 |
Q93038 | Q15628 | 2 | binding | up-regulates | 0.739 | Dr3 induces apoptosis by tradd-mediated recruitment of fadd and caspase-8 | SIGNOR-100480 |
P49336 | P46527 | 1 | phosphorylation | down-regulates | 0.289 | As a consequence, CDK8 overexpression promoted p27 degradation, whereas CDK8 knockdown reduced it.|We also show that CDK8 promotes phosphorylation of p27 at T187 and then induces p27 ubiquitination and degradation in a Skp2-dependent manner. | SIGNOR-278513 |
P17252 | P18031 | 1 | phosphorylation | up-regulates activity | 0.249 | PKC\u03b1 then phosphorylates and activates endothelial cell protein tyrosine phosphatase 1B (PTP1B) , . | SIGNOR-279257 |
Q9BQI3 | P05198 | 1 | phosphorylation | down-regulates activity | 0.89 | HRI is an intracellular heme sensor that coordinates heme and globin synthesis in erythropoiesis by inhibiting protein synthesis of globins and heme biosynthetic enzymes during heme deficiency. HRI is a heme-regulated kinase that phosphorylates the α-subunit of eIF2 in heme deficiency, impairing another round of trans... | SIGNOR-251817 |
P49841 | P60484 | 1 | phosphorylation | down-regulates activity | 0.424 | Gsk3beta Phosphorylates pten at thr-366 in intact cells phosphorylation of pten at thr-366 reduces the activity of pten in cells | SIGNOR-236641 |
P15336 | Q02930 | 2 | binding | up-regulates activity | 0.631 | CRE-BPa specifically binds to CRE as a homodimer or heterodimer with c-Jun or CRE-BP1. In CAT cotransfection experiments using CV-1 cells, transient expression of each of four CRE-BPa proteins caused a 1.6- to 3.4-fold increase of CRE-dependent transcription | SIGNOR-219655 |
Q00535 | Q13224 | 1 | phosphorylation | down-regulates quantity | 0.443 | Cdk5 phosphorylates NR2B at Ser1116 and controls surface level expression.|Reduction in Cdk5 activity, as well as disruption of Cdk5-NR2B interactions consistently increased NR2B surface levels and facilitated NMDA mediated synaptic function. | SIGNOR-278265 |
Q93008 | P62979 | 1 | cleavage | up-regulates quantity | 0.504 | Here we provide data suggesting that two of the four mammalian ubiquitin precursors, UBA52 and UBA80, are processed mostly post-translationally whereas the other two, UBB and UBC, probably undergo a combination of co- and post-translational processing. Using an unbiased biochemical approach we found that UCHL3, USP9X, ... | SIGNOR-270826 |
O15550 | P15036 | 1 | transcriptional regulation | down-regulates quantity by repression | 0.2 | Our findings reveal a dual role for UTX in suppressing acute myeloid leukaemia via repression of oncogenic ETS and upregulation of tumor suppressive GATA programs. several ETS transcription factors, including Elf4, Etv6, Erg, Fli1, Ets2, Spi1 and Elk3 were upregulated immediately after Utx loss in the preleukaemic phas... | SIGNOR-260035 |
P17252 | P05023 | 1 | phosphorylation | down-regulates activity | 0.329 | Parathyroid hormone (PTH) inhibits Na+,K+-ATPase activity through protein kinase C- (PKC) and extracellular signal-regulated kinase- (ERK) dependent pathways and increases serine phosphorylation of the α1-subunit. These results suggest that PTH regulates Na(+),K(+)-ATPase by PKC and ERK-dependent alpha(1)-subunit phos... | SIGNOR-262941 |
P62993 | Q13480 | 2 | binding | up-regulates | 0.873 | The gab1 docking protein forms a platform for the assembly of a multiprotein signaling complex downstream from receptor tyrosine kinases. In general, recruitment of gab1 occurs indirectly, via the adapter protein grb2 | SIGNOR-235917 |
Q16539 | P04637 | 1 | phosphorylation | up-regulates activity | 0.773 | P38 regulates p53, but also in p53-defective tumor cells rewire their checkpoint response and become dependent in the p38/mk2 pathway in mcf-7 cells, p38 kinase activated p53 more effectively than other members of the ras pathway. p53 and p38 kinase exist in the same physical complex, and co-expression of p38 stabilize... | SIGNOR-155246 |
Q9H6Z9 | Q16665 | 1 | hydroxylation | down-regulates quantity by destabilization | 0.797 | There are three EglN family members in humans and mice (EglN1, EglN2, and EglN3). Their enzymatic activity requires oxygen, ascorbic acid, iron, and α-ketoglutarate (α-KG). Under hypoxic conditions, EglNs lose their activity and fail to hydroxylate HIFα, which leads to HIFα stabilization | SIGNOR-262000 |
Q02750 | P06493 | 0 | phosphorylation | down-regulates | 0.496 | P34cdc2 catalyzes the in vitro phosphorylation of mkk1 on both of these threonine residues and inactivates mkk1 enzymatic activity. Both sites are phosphorylated in vivo as well | SIGNOR-36116 |
P03372 | P00533 | 0 | phosphorylation | up-regulates | 0.59 | Activation of estrogen receptor-alpha (eralpha) by growth factors in the absence of estrogen is a well-documented phenomenon.Egfr tyrosine kinase in vitro stimulated the phosphorylation of recombinant er | SIGNOR-115734 |
Q9H2S1 | Q05086 | 0 | ubiquitination | up-regulates activity | 0.286 | UBE3A directly ubiquitinates SK2 in the C-terminal domain, which facilitates endocytosis. | SIGNOR-278527 |
Q92949 | P41208 | 1 | transcriptional regulation | up-regulates quantity by expression | 0.353 | FOXJ1 expression in basal cells induced the expression of a panel of cilia-associated genes, including centrin 2 (CETN2); dynein, axonemal, heavy chain 11 (DNAH11); dynein, axonemal, intermediate chain 1 (DNAI1); dynein, axonemal, light intermediate chain 1 (DNALI1); EF-hand domain, C-terminal, containing 1 (EFHC1); sp... | SIGNOR-266930 |
P52564 | P19525 | 0 | phosphorylation | up-regulates activity | 0.2 | Consistent with this observation, PKR was capable of activating MKK6 as assessed in a coupled kinase assay containing the components of the p38 MAPK pathway.|In vitro kinase assays revealed that MKK6 was efficiently phosphorylated by PKR, and this could be inhibited by 2-aminopurine. | SIGNOR-279707 |
Q86XR7 | O60603 | 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 |
Q07666 | Q13882 | 0 | phosphorylation | up-regulates | 0.748 | Sik/brk is the first identified tyrosine kinase that can phosphorylate sam68 and regulate its activity within the nucleus, where it resides during most of the cell cycle | SIGNOR-80020 |
Q86VP1 | Q15025 | 0 | relocalization | up-regulates activity | 0.45 | ABIN1 interacted with the A20 regulatory molecule TAX1BP1 and was essential for the recruitment of TAX1BP1 and A20 to the noncanonical IkappaB kinases TBK1 and IKKi in response to poly(I:C) transfection. ABIN1 and TAX1BP1 together disrupted the interactions between the E3 ubiquitin ligase TRAF3 and TBK1/IKKi to attenua... | SIGNOR-275735 |
P45984 | P16615 | 1 | phosphorylation | up-regulates activity | 0.2 | JNK2 Enhances SERCA2 Function in a CaMKII-Independent Manner..|We found that JNK2 and SERCA2 proteins are physically associated with each other, and that JNK2 directly elevates the maximal rate of the SERCA2 activity by phosphorylating SERCA2. | SIGNOR-279540 |
P13640 | Q16236 | 0 | transcriptional regulation | up-regulates quantity by expression | 0.286 | NFE2L2 is stabilized and translocates to the nucleus, where it dimerizes with sMAF proteins. This complex binds to AREs to mediate the transcription of genes involved in iron metabolism, GSH metabolism, and ROS detoxification. The expression of MT1G during ferroptosis is regulated by the NFE2L2 signaling pathway. In th... | SIGNOR-279866 |
P27361 | Q00613 | 1 | phosphorylation | down-regulates | 0.631 | Sequential phosphorylation of hsf1 by mitogen-activated protein kinase and glycogen synthase kinase 3 at ser-303 and ser-307 represses transcriptional activation by heat shock factor-1. | SIGNOR-44999 |
O75197 | Q14332 | 2 | binding | up-regulates activity | 0.688 | Here we report that Wnt receptor Frizzled (Frz) and theco-receptors LRP5 and LRP6 (LRP5/6) directly interact with each other and this interaction is regulated by the LRP6 ectodomain. | SIGNOR-258968 |
P00748 | P39900 | 0 | cleavage | down-regulates quantity by destabilization | 0.33 | The data presented in this study show for the first time the degradation of Factor XII of the blood clotting system by matrix metalloproteinases. MMP-12, MMP-13, and MMP-14 cleave at Gly376Leu377|However, no activity of Factor XII can be observed after MMPinduced cleavage. | SIGNOR-263611 |
Q9NRM7 | P11908 | 1 | 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-276507 |
P52789 | O14867 | 0 | transcriptional regulation | up-regulates quantity | 0.2 | BACH1 activates transcription of Hexokinase 2 and Gapdh and increases glucose uptake, glycolysis rates, and lactate secretion, thereby stimulating glycolysis-dependent metastasis of mouse and human lung cancer cells. | SIGNOR-259338 |
P49841 | Q7KZI7 | 1 | phosphorylation | down-regulates activity | 0.349 | MARK family kinases can be activated by phosphorylation of a conserved threonine (Thr-208 in MARK2), and inactivated by phosphorylation of a serine (Ser-212), both in the activation loop of the catalytic domain. Activation is achieved by the kinases MARKK/TAO1 or LKB1, although the inactivating kinase was unknown. We s... | SIGNOR-276163 |
Q9UHD2 | Q8N3F0 | 2 | binding | down-regulates activity | 0.2 | Here we report that viral infection induced upregulation of INKIT, an inhibitor for NF-κB and IRF3 that restricted innate antiviral responses by blocking phosphorylation of p65 and IRF3. Viral infection induced IKK-mediated phosphorylation of INKIT at Ser58, resulting in its dissociation from the IKKs. INKIT is associa... | SIGNOR-273664 |
Q15669 | P63000 | 1 | relocalization | down-regulates activity | 0.41 | Therefore, RhoH functions as a Rac1 antagonist by inhibiting Rac1 translocation to the cell plasma membrane in the regulation of cell migration and F-actin assembly of HPCs | SIGNOR-259085 |
O43474 | O14770 | 2 | binding | up-regulates activity | 0.268 | We show that the Pbx1 and Meis2 homeodomain proteins interact with Klf4 and can be recruited to DNA elements comprising a Klf4 site or G C box, with adjacent Meis and Pbx sites. Meis2d and Pbx1a activate expression of p15(Ink4a) and E-cadherin, dependent on the Meis2d transcriptional activation domain. We suggest a mod... | SIGNOR-267238 |
P42229 | Q07817 | 1 | transcriptional regulation | up-regulates quantity by expression | 0.653 | FLT3-ITD-TKD dual mutants induce hyperactivation of STAT5 and up-regulation of its downstream targets Bcl-x(L) and RAD51 in Ba/F3 cells | SIGNOR-261551 |
P67775 | P29372 | 0 | polyubiquitination | down-regulates quantity by destabilization | 0.2 | Here we report that MID1 catalyzes the in vitro ubiquitination of the catalytic subunit of PP2A (PP2Ac) in the absence of alpha4. In the presence of alpha4, the level of PP2Ac ubiquitination is reduced.The high molecular weight smear pattern was not as obvious, suggesting that domains within the C-terminal half of MID1... | SIGNOR-271930 |
Q16539 | O60381 | 1 | phosphorylation | up-regulates | 0.43 | A mutation of the p38 map kinase phosphorylation site at aa 401 [(s-a)401hbp1] also triggered hbp1 protein instability. While protein stability was compromised by mutation, the specific activities of (s-a)401hbp1 and of wild-type hbp1 appeared comparable for transcriptional repression. | SIGNOR-119138 |
Q9UNE7 | P29034 | 1 | polyubiquitination | down-regulates quantity by destabilization | 0.318 | S100 protein itself is ubiquitinated by CHIP in a Ca2+-dependent manner.Ubiquitylated S100 proteins are shown as (Ub)n-S100A2 and (Ub)n-S100P. The association of the S100 proteins with CHIP provides a Ca2+-dependent regulatory mechanism for the ubiquitination and degradation of intracellular proteins by the CHIP-protea... | SIGNOR-272918 |
P35568 | P53350 | 0 | phosphorylation | down-regulates activity | 0.267 | Phosphorylation of ser24 in the pleckstrin homology domain of insulin receptor substrate-1 by mouse pelle-like kinase/interleukin-1 receptor-associated kinase| irs-1 mutants s24d or s24e (mimicking phosphorylation at ser(24)) had impaired ability to associate with insulin receptors resulting in diminished tyrosine phos... | SIGNOR-135688 |
O95631 | P60709 | 1 | post transcriptional regulation | up-regulates quantity | 0.28 | Netrin-1 induces β-actin translation driven by its 3’UTR. | SIGNOR-268161 |
P53350 | Q13485 | 1 | phosphorylation | down-regulates quantity by destabilization | 0.254 | We observed that PLK1 could significantly promote the ubiquitination and degradation of Smad4 wild type, Smad4 S171A, Smad4 S187A, Smad4 S191A, respectively, but PLK1-induced the ubiquitination and degradation of Smad4 T197A were obviously inhibited (Fig. 1M). | SIGNOR-277591 |
P17612 | P36382 | 1 | phosphorylation | up-regulates activity | 0.307 | Gap junction channels formed of Cx40 are modulated by protein-kinase-A-mediated phosphorylation. Macroscopic conductance and permeability of Cx40 gap junctions is strongly increased by cAMP. two serine residues that can be phosphorylated by PKA, S120 and S345 | SIGNOR-249982 |
O14672 | P04626 | 1 | cleavage | up-regulates activity | 0.344 | The ADAM proteases are best known for their role in shedding the extracellular domain of transmembrane proteins. Among the transmembrane proteins shed by ADAM10 are notch, HER2, E-cadherin, CD44, L1 and the EGFR ligands, EGF and betacellulin. | SIGNOR-259845 |
O14965 | P17612 | 0 | phosphorylation | up-regulates activity | 0.512 | Aurora2 is regulated by phosphorylation. phosphorylation occurs on a conserved residue, Threonine 288, within the activation loop of the catalytic domain of the kinase and results in a significant increase in the enzymatic activity. Threonine 288 resides within a consensus motif for the cAMP dependent kinase and can be... | SIGNOR-250337 |
Q05519 | Q14114 | 1 | post transcriptional regulation | up-regulates quantity by stabilization | 0.2 | We demonstrate that SFRS11 directly binds to the 3' UTR of LRP8 mRNA, as well as to the third exon of apoE mRNA, resulting in stabilization of these mRNAs, eventually deactivating JNK signaling. | SIGNOR-269670 |
Q02156 | P49841 | 2 | phosphorylation | down-regulates activity | 0.268 | However, PKCepsilon and Akt can also phosphorylate GSK3beta directly. | SIGNOR-279101 |
P42772 | Q9HCX3 | 0 | transcriptional regulation | down-regulates quantity by repression | 0.28 | Finally, we show that ZNF304 also directs transcriptional silencing of INK4-ARF in human embryonic stem cells. | SIGNOR-266099 |
Q99527 | P63092 | 2 | binding | up-regulates activity | 0.377 | GPCRs transduce their signal via G-protein heterotrimers (αβγ) that dissociate in free Gα-subunit protein and Gβγ-subunit protein complexes following ligand stimulation; the activated receptor induces a conformational change in the associated G protein α-subunit leading to release of GDP followed by binding of GTP and ... | SIGNOR-251102 |
P50148 | P30559 | 2 | binding | up-regulates activity | 0.552 | OT binds to its cognate G protein–coupled receptor (OTR) and exerts diverse effects, including stimulation (Gs) or inhibition (Gi/o) of adenylyl cyclase, stimulation of potassium channel currents (Gi), and activation of phospholipase C (Gq). | SIGNOR-270332 |
Q86YJ5 | P15151 | 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 aci... | SIGNOR-271530 |
P22455 | P10767 | 2 | binding | up-regulates | 0.732 | Our results establish an fgf binding profile for fgfr-4 with afgf having the highest affinity, followed by k-fgf/hst-1 and bfgf. In addition, fgf-6 was found to bind to fgfr-4 in ligand competition experiments. Ligands binding to fgfr-4 induced receptor autophosphorylation and phosphorylation of a set of cellular polyp... | SIGNOR-18570 |
P15509 | P09603 | 2 | binding | up-regulates | 0.337 | Granulocyte-macrophage colony-stimulating factor (gm-csf) is an important hematopoietic cytokine that exerts its effects by interaction with the gm-csf receptor (gmr) on the surface of responsive cells. The gm-csf receptor consists of two subunits: gmralpha, which binds gm-csf with low affinity, and gmrbeta, which lack... | SIGNOR-72455 |
O96017 | P06400 | 1 | phosphorylation | up-regulates activity | 0.423 | Phosphorylation of prb at ser612 by chk1/2 leads to a complex between prb and e2f-1 after dna damageprb inhibits cell cycle progression through interactions with the e2f family of transcription factors. Here, we report that dna damage induced not only the dephosphorylation of prb at cdk phosphorylation sites and the bi... | SIGNOR-153908 |
P51608 | Q13451 | 1 | transcriptional regulation | down-regulates quantity by repression | 0.306 | These results are compatible with the hypothesis that MeCP2 associates with the Sgk and Fkbp5 promoters and has a repressive effect that is over-ridden by elevated glucocorticoids in response to stress. | SIGNOR-264542 |
P60484 | Q9H4B4 | 0 | phosphorylation | down-regulates activity | 0.335 | Plk3 phosphorylates pten on thr-366 and ser-370. Plk3-mediated phosphorylation facilitates pten stabilization, thereby negatively regulating the pi3k/pdk1/akt1 signaling axis | SIGNOR-168473 |
P42345 | Q9UBS0 | 1 | phosphorylation | up-regulates | 0.834 | In response to insulin and nutrients, mtorc1, consisting of mtor, raptor (regulatory-associated protein of mtor), and mlst8, is activated and phosphorylates eukaryotic initiation factor 4e-binding protein (4ebp) and p70 s6 kinase to promote protein synthesis and cell size. | SIGNOR-154821 |
P51608 | O00141 | 1 | transcriptional regulation | down-regulates quantity by repression | 0.292 | These results are compatible with the hypothesis that MeCP2 associates with the Sgk and Fkbp5 promoters and has a repressive effect that is over-ridden by elevated glucocorticoids in response to stress. | SIGNOR-264543 |
Q9UL68 | O75182 | 2 | binding | up-regulates activity | 0.45 | We found that the pan neuron-specific transcription factor Myt1-like (Myt1l) exerts its pro-neuronal function by direct repression of many different somatic lineage programs except the neuronal program. The repressive function of Myt1l is mediated via recruitment of a complex containing Sin3b by binding to a previously... | SIGNOR-266774 |
P61006 | Q9Y6E0 | 0 | phosphorylation | up-regulates activity | 0.275 | In a screen for Rab8A kinases we identify TAK1 and MST3 kinases that can efficiently phosphorylate the Switch II residue Threonine72 (Thr72) in a similar manner as LRRK2 in vitro. |Overall our data suggests that the phosphorylation of Rab8A at Ser111 may influence Switch II-binding by regulators, thus disrupting intera... | SIGNOR-260265 |
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