IdA string | IdB string | labels int64 | mechanism string | effect string | score float64 | sentence string | signor_id string |
|---|---|---|---|---|---|---|---|
Q9NR28 | P45983 | 0 | phosphorylation | up-regulates activity | 0.371 | JNK1\u2011mediated phosphorylation of Smac/DIABLO at the serine 6 residue is functionally linked to its mitochondrial release during TNF\u2011\u03b1-\u2011induced apoptosis of HeLa cells. | SIGNOR-280029 |
Q96GD4 | Q9NS23 | 1 | phosphorylation | down-regulates | 0.438 | Here, we show that aurora a and b associate with and phosphorylate rassf1a on serine 203 aurora a regulates prometaphase progression by inhibiting the ability of rassf1a to suppress apc-cdc20 activity. | SIGNOR-184561 |
P15531 | P06493 | 0 | phosphorylation | up-regulates | 0.266 | Application of this approach to the discovery of cdk1-cyclin b substrates yielded identification of >70 substrates and phosphorylation sites. Many of these sites are known to be phosphorylated in vivo, but most of the proteins have not been characterized as cdk1-cyclin b substrates. | SIGNOR-160493 |
Q92911 | P01222 | 0 | 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 its half-life, and retaining NIS at the thyrocyte plasma membrane | SIGNOR-251995 |
Q12913 | P06241 | 0 | phosphorylation | up-regulates activity | 0.366 | We demonstrate here that DEP-1 is phosphorylated in a Src- and Fyn-dependent manner on Y1311 and Y1320, which bind the Src SH2 domain. This allows DEP-1-catalyzed dephosphorylation of Src inhibitory Y529 and favors the VEGF-induced phosphorylation of Src substrates VE-cadherin and Cortactin. | SIGNOR-276372 |
O76090 | Q05655 | 0 | phosphorylation | down-regulates activity | 0.2 | We have identified a PKC phosphorylation site (S358) located in the C terminal region of hBest1 critical for channel rundown. Phosphorylation of this site by PKC activators and PP2A inhibitors reduces channel rundown. | SIGNOR-260880 |
Q9P275 | P22087 | 1 | deubiquitination | up-regulates quantity by stabilization | 0.361 | USP36 deubiquitylated the nucleolar proteins nucleophosmin/B23 and fibrillarin, and stabilized them by counteracting ubiquitylation-mediated proteasomal degradation. | SIGNOR-272291 |
P57058 | O43736 | 1 | phosphorylation | up-regulates activity | 0.2 | ITM2A is phosphorylated at T35 and the phosphorylation status of ITM2A contributes to breast cancer proliferation. Moreover, we found that ITM2A was phosphorylated at T35 by HUNK, a serine/threonine kinase significantly correlated with human breast cancer overall survival and HER2-induced mammary tumorigenesis. | SIGNOR-273640 |
Q99717 | Q9HAU4 | 0 | ubiquitination | down-regulates | 0.736 | 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-193378 |
Q9NZN5 | P61586 | 1 | guanine nucleotide exchange factor | up-regulates activity | 0.905 | 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 among regulators, but also that the inactivating RhoGAPs are less selective than the activating RhoGEFs (p-value=0.02)(Supplementary Table 2). | SIGNOR-260539 |
Q16665 | O94953 | 1 | transcriptional regulation | up-regulates quantity by expression | 0.261 | 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, KDM6B, and KDM7A) or repressed (KDM NO66 and KDM1A) by both HIF-1a and HIF-2a. | SIGNOR-271569 |
Q8N163 | Q13315 | 0 | phosphorylation | up-regulates activity | 0.587 | Here, we report that, in human cell lines, DNA damage triggered the phosphorylation of DBC1 on Thr454 by ATM (ataxia telangiectasia-mutated) and ATR (ataxia telangiectasia and Rad3-related) kinases. Phosphorylated DBC1 bound to and inhibited SIRT1, resulting in the dissociation of the SIRT1-p53 complex and stimulating p53 acetylation and p53-dependent cell death. | SIGNOR-267661 |
P68400 | Q9UPP1 | 1 | phosphorylation | up-regulates activity | 0.2 | The CK2 kinase is responsible for PHF8 phosphorylation at Ser854. PHF8 is phosphorylated by CK2, which regulates binding of PHF8 to TopBP1. The Ser854 residue of PHF8 is required for its interaction with TopBP1. | SIGNOR-273628 |
O15553 | Q16513 | 0 | phosphorylation | down-regulates activity | 0.349 | PKNs bind to human pyrin and phosphorylate S208 and S242. Pyrin forms an inflammasome when mutant or in response to bacterial modification of the GTPase RhoA. We found that RhoA activated the serine-threonine kinases PKN1 and PKN2 that bind and phosphorylate pyrin. Phosphorylated pyrin bound to 14-3-3 proteins, regulatory proteins that in turn blocked the pyrin inflammasome. | SIGNOR-275464 |
P53350 | P62826 | 1 | phosphorylation | up-regulates | 0.264 | Plk1 is capable of phosphorylating co-immunoprecipitated ran in vitro on serine-135 and ran is phosphorylated in vivo at the same site during mitosis when plk1 is normally activated. Deregulation of ran phosphorylation disrupts normal spindle structure and segregation of chromosomes. | SIGNOR-149073 |
P06493 | Q96FF9 | 1 | phosphorylation | down-regulates activity | 0.711 | Here we show that the mitotic kinases Aurora B and Cyclin-dependent kinase 1 (Cdk1) destabilize interactions between Sororin and the cohesin subunit precocious dissociation of sisters protein 5 (Pds5) by phosphorylating Sororin, leading to release of acetylated cohesin from chromosome arms and loss of cohesion. | SIGNOR-276118 |
Q8N4C6 | Q15154 | 0 | relocalization | up-regulates | 0.406 | Rna silencing of pcm-1 leads to reduced assembly of centrin, pericentrin, and ninein at the centrosome | SIGNOR-95077 |
Q13541 | P06493 | 0 | phosphorylation | down-regulates activity | 0.397 | Phosphorylation of 4e-bp1 is critical in causing its dissociation from eif-4e, leaving 4e available to form translationally active eif-4f complexes, switching on mrna translation. We show that the cyclin-dependent kinase, cdc2, phosphorylates 4e-bp1 at thr-70 and that phosphorylation of this site is permissive for ser-65 phosphorylation. Crucially, the increased phosphorylation of 4e-bp1 during mitosis results in its complete dissociation from eif-4e. | SIGNOR-110416 |
Q9UER7 | Q86Z02 | 0 | phosphorylation | down-regulates activity | 0.611 | HIPK1 phosphorylates Daxx on Ser 669, and phosphorylation of this site is important in modulating the ability of Daxx to function as a transcriptional repressor. | Therefore, phosphorylation at Ser 669 by HIPK1 diminishes the ability of Daxx to repress transcription. | SIGNOR-260842 |
Q9UBS5 | P33176 | 0 | relocalization | up-regulates activity | 0.255 | GABABR1 co-immunoprecipitated with Marlin-1 and kinesin-I, providing evidence for the existence of a complex between these proteins. Kinesin-I modulates GABAB receptor transport. | SIGNOR-260990 |
Q05923 | P28482 | 1 | dephosphorylation | down-regulates | 0.745 | Pac1 and mkp-1 previously have been implicated in the in vivo inactivation of erk or of erk and jnk, respectively. | SIGNOR-40915 |
Q16695 | Q96T68 | 0 | methylation | up-regulates activity | 0.2 | Here, we have characterized a previously undescribed member of the histone H3K9 methyltransferase family named CLLD8 (or SETDB2 or KMT1F). This protein contributes to the trimethylation of both interspersed repetitive elements and centromere-associated repeats and participates in the recruitment of heterochromatin protein 1 to centromeres. Methylation of histone H3 at lysine 9 (H3K9) has emerged as an important player in the formation of heterochromatin, chromatin condensation, and transcriptional repression. | SIGNOR-263895 |
P00533 | P14618 | 1 | phosphorylation | down-regulates activity | 0.449 | EGFR binds to and phosphorylates PKM2 to inhibit its activity. | SIGNOR-277197 |
P07900 | Q9ULT8 | 0 | ubiquitination | down-regulates quantity | 0.2 | We demonstrate that Hectd1 is a functional ubiquitin ligase and that one of its substrates is Hsp90, a chaperone protein with both intra- and extracellular clients. Identification of Hsp90 in both proteomic screens suggested that members of the Hsp90 superfamily may be substrates of Hectd1. Myc-Hectd1ANK and HA-Hsp90bd (the fragment identified in the yeast two-hybrid screen) bind in an in vitro binding assay (Fig. 3 D) and when coexpressed in HEK293T cells. Hectd1 is required for K63-linked Ubn of Hsp90. Together, these results demonstrate that Hectd1-dependent Ubn of Hsp90 targets it away from the membrane and the secretory pathway. | SIGNOR-261199 |
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 components of desmosomes (desmoplakin) and increased interaction with adherens junction proteins (α-catenin) | SIGNOR-251134 |
P78337 | P00519 | 0 | phosphorylation | up-regulates activity | 0.2 | Notably, c-Abl controls augmentation of Pitx1 at the post-transcriptional level.|Overexpression of c-Abl induces tyrosine phosphorylation of Pitx1, either directly or indirectly. | SIGNOR-280171 |
Q92934 | Q15418 | 0 | phosphorylation | down-regulates activity | 0.395 | We report here that the phosphorylation of BAD at Ser-155 within the BH3 domain is a second phosphorylation-dependent mechanism that inhibits the death-promoting activity of BAD. Protein kinase A, RSK1, and survival factor signaling stimulate phosphorylation of BAD at Ser-155, blocking the binding of BAD to Bcl-XL. RSK1 phosphorylates BAD at both Ser-112 and Ser-155 and rescues BAD-mediated cell death in a manner dependent upon phosphorylation at both sites. | SIGNOR-249045 |
P24941 | P53350 | 1 | phosphorylation | up-regulates activity | 0.375 | Thus, CycA2-CDK2 can stimulate phosphorylation of PLK1 T210 in vitro and the interactions required for CycA2-mediated PLK1 T210 phosphorylation are detected in the cytoplasm, but not in the nucleus.|We find that Cyclin A2-CDK2 can activate the mitotic kinase PLK1 through phosphorylation of Bora, and that only cytoplasmic Cyclin A2 interacts with Bora and PLK1. | SIGNOR-280212 |
Q71DI3 | Q14493 | 0 | translation regulation | up-regulates quantity by expression | 0.2 | Synthesis of mature histone mRNA requires only a single processing reaction: an endonucleolytic cleavage between a conserved stem-loop and a purine-rich downstream element to form the 3' end. The stem-loop binding protein (SLBP) is required for processing, and following processing, histone mRNA is transported to the cytoplasm, where SLBP participates in translation of the histone mRNA|We used radiolabeled probes generated by PCR targeting the open reading frame (ORF) to detect histones H2A, H2B, H3, H4, and H1 and used 7SK snRNA as a loading control (Fig. 2A). The abundance of histone H2A, H2B, H3, and H4 mRNAs is reduced to 37% to 70% of control levels in the SLBP knockdown cells when compared to the C2 control. | SIGNOR-265414 |
Q13153 | Q13233 | 1 | phosphorylation | up-regulates activity | 0.538 | We found that pak1 phosphorylated mekk1 on serine 67 of its amino-terminal regulatory domain. mekk1 activity was increased modestly following pak phosphorylation. | SIGNOR-236006 |
Q14524 | Q13557 | 0 | phosphorylation | down-regulates | 0.492 | A stable interaction between ?(C)-camkii and the intracellular loop between domains 1 and 2 of na(v)1.5 was observed. This region was also phosphorylated by ?(C)-camkii, specifically at the ser-516 and thr-594 sites.Wild-type (wt) and phosphomutant hna(v)1.5 were co-expressed with gfp-?(C)-camkii in hek293 cells, and i(na) was recorded. As observed in myocytes, camkii shifted wt i(na) availability to a more negative membrane potential and enhanced accumulation of i(na) into an intermediate inactivated state, but these effects were abolished by mutating either of these sites to non-phosphorylatable ala residues. | SIGNOR-197058 |
P46020 | P22612 | 0 | phosphorylation | down-regulates activity | 0.325 | Phosphorylation of the alpha and beta subunits by the 3',5'-cyclic adenosine monophosphate (cAMP)-dependent protein kinase (PKA) also relieves inhibition of the gamma subunit and thereby activates the enzyme. | SIGNOR-267415 |
Q9UN36 | O00141 | 0 | phosphorylation | up-regulates | 0.395 | Sgk1 phosphorylated ndrg2 at thr330, ser332 and thr348 in vitro. for example, the phosphorylation of thr330 or ser332 by sgk1 may prime ndrg2 for phosphorylation by gsk3 at ser326 and ser328 respectively, for example, the phosphorylation of thr330 or ser332 by sgk1 may prime ndrg2 for phosphorylation by gsk3 at ser326 and ser328 respectively, the phosphorylation of thr348 by sgk1 may prime for phosphorylation at ser344 | SIGNOR-129676 |
P49418 | P28482 | 0 | phosphorylation | down-regulates activity | 0.265 | Thus, we propose that mapk phosphorylation of amphiphysin1 controls ngf receptor/trka-mediated endocytosis by terminating the amphiphysin1-ap-2 interaction.Our results indicate that phosphorylation of amphiphysin 1 at ser-285 and/or ser-293 affects the function of amphiphysin1.Mapk phosphorylation of ser-285 and ser-293 could modulate the interaction between prd and ap-2, resulting in the dissociation of amphiphysin1 from ap-2. | SIGNOR-126859 |
O15111 | P25963 | 1 | phosphorylation | down-regulates quantity by destabilization | 0.896 | We described the purification of a 900 kda protein kinase complex, the ikb kinase (ikk), that phosphorylates ikbalfa and ikbbeta at the sites that mediate their ubiquitination and degradation | SIGNOR-52875 |
P11908 | Q13131 | 0 | phosphorylation | down-regulates activity | 0.2 | We demonstrate here that glucose deprivation or hypoxia results in the AMPK-mediated phosphorylation of phosphoribosyl pyrophosphate synthetase 1 (PRPS1) S180 and PRPS2 S183, leading to conversion of PRPS hexamers to monomers and thereby inhibiting PRPS1/2 activity, nucleotide synthesis, and nicotinamide adenine dinucleotide (NAD) production. | SIGNOR-265731 |
P63000 | Q86VW2 | 0 | guanine nucleotide exchange factor | up-regulates | 0.622 | Exogenous expression of geft promotes myogenesis ofc2c12 cells via activation of rhoa, rac1, and cdc42 and their downstream effector proteins, while a dominant negative mutant of geft inhibits this process. | SIGNOR-236882 |
Q14012 | Q96RR4 | 0 | phosphorylation | up-regulates activity | 0.413 | Human calcium-calmodulin dependent protein kinase I: cDNA cloning, domain structure and activation by phosphorylation at threonine-177 by calcium-calmodulin dependent protein kinase I kinase. | SIGNOR-250716 |
P17096 | Q13315 | 0 | phosphorylation | up-regulates activity | 0.2 | 21 As shown in Fig. 2 b, ATM was able to phosphorylate in vitro the C-terminal peptide of HMGA1. | SIGNOR-279493 |
Q14814 | P23409 | 1 | transcriptional regulation | up-regulates quantity by expression | 0.573 | Myogenin and MEF2 function synergistically to activate the MRF4 promoter during myogenesis. | SIGNOR-238715 |
O14757 | O75461 | 1 | phosphorylation | down-regulates activity | 0.574 | the checkpoint kinase Chk1 phosphorylates E2F6 leading to its dissociation from promoters. | SIGNOR-266371 |
O14757 | Q53H47 | 1 | phosphorylation | down-regulates activity | 0.49 | We previously found that Chk1 phosphorylation of Metnase on S495 enhanced its DNA DSB repair activity but decreased its ability to re-start stalled replication forks. Here we show that phosphorylated Metnase feeds back to increase the half-life of Chk1. Chk1 half-life is regulated by DDB1 targeting it to Cul4A for ubiquitination and destruction. Metnase decreases Chk1 interaction with DDB1, and decreases Chk1 ubiquitination. | SIGNOR-273610 |
Q16665 | P49841 | 0 | phosphorylation | down-regulates activity | 0.332 | Glycogen synthase kinase 3 \u03b2 (GSK3\u03b2) phosphorylates HIF-1\u03b1 at three serine residues (Ser-551, Ser-555, and Ser-589) located within its oxygen-dependent degradation domain (ODDD) [12] (Figure 5). Phosphorylation at these residues by GSK3\u03b2 enhances HIF-1\u03b1 degradation in a pVHL-independent manner, resulting in suppression of the HIF-1 activity [12,13].|Phosphorylation at these residues by GSK3beta enhances HIF-1alpha degradation in a pVHL independent manner, resulting in suppression of the HIF-1 activity , ]. | SIGNOR-278294 |
Q01628 | P06241 | 0 | phosphorylation | up-regulates quantity | 0.452 | We determined that both mouse and human IFITM3 are phosphorylated by the protein-tyrosine kinase FYN on tyrosine 20 (Tyr(20)). Phosphorylation of IFITM3 on Tyr20 Leads to Plasma Membrane Accumulation. | SIGNOR-266304 |
P00441 | P19544 | 0 | transcriptional regulation | up-regulates quantity by expression | 0.265 | The human copper-zinc superoxide dismutase gene (SOD1) proximal promoter is regulated by Sp1, Egr-1, and WT1 via non-canonical binding sites. Egr-1 and two splicing variants of the Egr-related protein WT1 were able to transactivate the SOD1 promoter in co-transfection experiments. | SIGNOR-253898 |
P29323 | O43426 | 1 | phosphorylation | down-regulates | 0.57 | Ephb2 causes tyrosine phosphorylation in the proline-rich domain of synaptojanin 1, and inhibits both the interaction with endophilin and the 5'-phosphatase activity of synaptojanin 1 | SIGNOR-135274 |
Q04759 | P35236 | 1 | phosphorylation | up-regulates activity | 0.2 | PKC θ is required for HePTP translocation to the immune synapse. PKC θ phosphorylates HePTP at S225 in primary T cells. | SIGNOR-276045 |
O95319 | P12931 | 0 | phosphorylation | up-regulates activity | 0.321 | Site-directed mutagenesis of putative tyrosine phosphorylation sites in CUGBP2 identified tyrosine 39 as a c-Src target, and a CUGBP2 with a mutated tyrosine 39 displayed an attenuated ability to bind COX-2 mRNA. | SIGNOR-263195 |
P09601 | Q16236 | 0 | transcriptional regulation | up-regulates quantity by expression | 0.679 | In both models, the inducer-modified and Nrf2-bound Keap1 is inactivated and, consequently, newly synthesized Nrf2 proteins bypass Keap1 and translocate into the nucleus, bind to the ARE and drive the expression of Nrf2 target genes such as NAD(P)H quinone oxidoreductase 1 (NQO1), heme oxygenase 1 (HMOX1), glutamate-cysteine ligase (GCL) and glutathione S transferases (GSTs). | SIGNOR-256276 |
P53778 | P15172 | 1 | phosphorylation | up-regulates activity | 0.446 | We determined that p38-gamma directly phosphorylated MyoD on Ser199 and Ser200, which results in enhanced occupancy of MyoD on the promoter of myogenin together with markedly decreased transcriptional activity. Phosphorylation of MyoD by p38-γ directs the assembly of a repressive transcriptional complex at the Myogenin promoter. | SIGNOR-276273 |
O15111 | Q07666 | 1 | phosphorylation | up-regulates activity | 0.2 | Sam68 is phosphorylated by IKK\u03b1 in the nucleus. | SIGNOR-278439 |
Q92570 | Q07812 | 1 | transcriptional regulation | up-regulates quantity by expression | 0.2 | Over-expression of NR4A3 attenuated proliferation of cancer cells and promoted apoptosis by augmenting the expression of pro-apoptotic genes, PUMA and Bax. | SIGNOR-259397 |
P48736 | P07951 | 1 | phosphorylation | up-regulates activity | 0.335 | Here, we demonstrate a requirement for the protein kinase activity of PI(3)K in agonist-dependent beta-adrenergic receptor (betaAR) internalization. Using PI(3)K mutants with either protein or lipid phosphorylation activity, we identify the cytoskeletal protein non-muscle tropomyosin as a substrate of PI(3)K, which is phosphorylated in a wortmannin-sensitive manner on residue Ser 61. A constitutively dephosphorylated (S61A) tropomyosin mutant blocks agonist-dependent betaAR internalization, whereas a tropomyosin mutant that mimics constitutive phosphorylation (S61D) complements the PI(3)K mutant, with only lipid phosphorylation activity reversing the defective betaAR internalization. | SIGNOR-263028 |
Q9P289 | P15311 | 1 | phosphorylation | up-regulates | 0.2 | Activation of ezrin is mediated by initial pip2 binding and subsequent phosphorylation of threonine 567. Mst4 phosphorylates the regulatory t567 residue of ezrin. | SIGNOR-185563 |
O00429 | Q13464 | 0 | phosphorylation | up-regulates activity | 0.314 | We have also previously reported that ROCK1-mediated Drp1S600 phosphorylation resulted in enhanced mitochondrial fission in podocytes | SIGNOR-262549 |
P06493 | O95139 | 1 | phosphorylation | up-regulates activity | 0.2 | Here, we show that a fraction of cyclin B1/Cdk1 proteins localizes to the matrix of mitochondria and phosphorylates a cluster of mitochondrial proteins, including the complex I (CI) subunits in the respiratory chain. Cyclin B1/Cdk1-mediated CI phosphorylation enhances CI activity, whereas deficiency of such phosphorylation in each of the relevant CI subunits results in impairment of CI function.|These results were confirmed by generating phosphorylation defective forms of the five CI subunits through substitutions of S/T residues with Alanine (A) on either Cdk1 optimal or minimal consensus motifs (T383 on NDUFV1, S105 on NDUFV3, S364 on NDUFS2, S55/S29/T5 on NDUFB6, and T142/T120 on NDUFA12). The mutation of Cdk1 consensus motifs severely diminished their phosphorylation | SIGNOR-275589 |
Q32MK0 | Q06413 | 1 | phosphorylation | up-regulates activity | 0.269 | Here, we show that phosphorylation of MEF2C on T(80) by skeletal myosin light chain kinase (skMLCK) enhances skeletal and not cardiac myogenesis.|Here, we show that skMLCK directly phosphorylates MEF2C, leading to p300/PCAF recruitment, increased acetylation of skeletal muscle-specific genes, and enhanced skeletal myogenesis | SIGNOR-264565 |
Q13950 | P28562 | 0 | dephosphorylation | up-regulates activity | 0.353 | In a separate study, MKP-1 was shown to induce osteogenesis by dephosphorylating Ser125 on Runx2 isoform type II (37).|MKP-1 increases RUNX2 activity and downregulates MAPK, cyclin D1 in differentiated osteoblasts inducing growth arrest and mineralization. | SIGNOR-277143 |
Q6STE5 | Q16539 | 0 | phosphorylation | up-regulates activity | 0.368 | P38 phosphorylates the baf60 subunit of the swi-snf chromatin remodelling complex, and p38 recruits this complex to differentiation-specific loci. | SIGNOR-176557 |
Q9NY61 | P07288 | 1 | transcriptional regulation | up-regulates quantity by expression | 0.2 | Chromatin immunoprecipitation in combination with siRNA-mediated knockdown revealed that recruitment of AATF and ZIPK to the PSA enhancer was dependent on AR, whereas recruitment of TSG101 was dependent on AATF. | SIGNOR-253669 |
Q9Y3M2 | P31749 | 0 | phosphorylation | up-regulates activity | 0.572 | These observations argue that Chibby is a bona fide Akt substrate and that Akt kinase phosphorylates Chibby at the serine 20 residue. | SIGNOR-279002 |
O95835 | Q14872 | 1 | phosphorylation | down-regulates activity | 0.2 | The Hippo pathway kinases LATS1 and LATS2 attenuate cellular responses to heavy metals through phosphorylating MTF1|the Hippo pathway kinase LATS phosphorylates and inhibits MTF1|LATS phosphorylates MTF1 at S152 and disrupts its association with the promoters of heavy metal response genes, resulting in the loss of heavy metal response gene expression | SIGNOR-275473 |
Q5TCX8 | O15111 | 1 | phosphorylation | down-regulates activity | 0.2 | Immunoprecipitation and in vitro kinase analysis revealed that MLK4 physically interacts with both IKKalpha and beta, but preferentially phosphorylates IKKalpha over IKKbeta (XREF_FIG | SIGNOR-279067 |
P17252 | Q13224 | 1 | phosphorylation | up-regulates activity | 0.469 | These results indicate that PKC can directly phosphorylate S1303 and S1323 in the NR2B C terminus, leading to enhanced currents through NMDA receptor channels. | SIGNOR-249083 |
Q9NRC8 | P68431 | 1 | deacetylation | up-regulates activity | 0.2 | SIRT7 links H3K18 deacetylation to maintenance of oncogenic transformation.|Genome-wide binding studies reveal that SIRT7 binds to promoters of a specific set of gene targets, where it deacetylates H3K18Ac and promotes transcriptional repression. | SIGNOR-275874 |
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 |
Q99828 | Q9UNE7 | 0 | ubiquitination | down-regulates quantity | 0.2 | All those were suggesting that CHIP promotes CIB1 ubiquitination via the Lys 48 residue of ubiquitin.|K10 and K65 were the Lysine (K) residues for CHIP mediated CIB1 degradation. | SIGNOR-278721 |
P49588 | P18848 | 0 | transcriptional regulation | up-regulates quantity by expression | 0.2 | QRICH1 promotes the expression of translation-related genes. our combined ChIP-seq and RNA-seq analyses identified that QRICH1 and ATF4 were enriched at the promoters of these specific tRNA synthetases, and that ER stress positively regulated their transcription (Fig. 4I). Together, these findings suggest that QRICH1 and ATF4 modulate tRNA metabolic processes to promote secreted protein synthesis during ER stress. | SIGNOR-269414 |
Q04771 | P36897 | 0 | phosphorylation | up-regulates activity | 0.364 | This directly demonstrates that TGFBR1 can activate ACVR1 in vivo.|We show that in response to TGF-\u03b2, TGFBRI phosphorylates and activates ACVR1, which phosphorylates SMAD1/5. | SIGNOR-279490 |
O14920 | Q96BF3 | 1 | phosphorylation | up-regulates activity | 0.2 | Manipulating the IκB kinase β activity coupled with in vivo and in vitro kinase assays demonstrated that IκB kinase β is a key serine/threonine kinase activated by autophagy stimuli and that it catalyzes phosphorylation of IGPR-1 at Ser220 The subsequent activation of IGPR-1, in turn, stimulates phosphorylation of AMP-activated protein kinase, which leads to phosphorylation of the major pro-autophagy proteins ULK1 and Beclin-1 (BECN1), increased LC3-II levels, and accumulation of LC3 punctum. | SIGNOR-273642 |
P52735 | P12931 | 0 | phosphorylation | up-regulates activity | 0.527 | Since we find that Vav2 is necessary for cell spreading and Src activity is necessary for Vav2 activation of Rac and lamellipodia formation, our data suggest a model of Rac activation by integrins that depends on Src phosphorylation of Vav2.|We did not detect increased Rac activation when Vav2 was cotransfected with activated Src, although Vav2 tyrosine phosphorylation was increased (data not shown), indicating that endogenous Src activity is sufficient to fully activate Vav2. | SIGNOR-280138 |
Q9ULU4 | O43623 | 1 | transcriptional regulation | down-regulates quantity by repression | 0.2 | Our quantitative ChIP experiments confirmed that ZMYND8 and JARID1D were co-localized at Slug, CD44, VEGFA, and EGFR genes (Figures 4F–4I). Our ChIP results also showed that ZMYND8 repressed and occupied other JARID1D target genes, such as the matrix metalloproteinase 1 (MMP1) and MMP3, that we previously reported | SIGNOR-262038 |
Q15831 | Q9H0K1 | 1 | phosphorylation | up-regulates | 0.481 | A total of 12 human kinases (nuak1, nuak2, brsk1, brsk2, qik, qsk, sik, mark1, mark2, mark3, mark4 and melk) are related to ampk. Here we demonstrate that lkb1 can phosphorylate the t-loop of all the members of this subfamily, apart from melk, increasing their activity >50-fold. | SIGNOR-122788 |
P46934 | Q13501 | 1 | ubiquitination | down-regulates quantity by destabilization | 0.277 | Depletion of NEDD4 dramatically reduced the LC3 protein level and elevated the SQSTM1 protein level.|Furthermore, SQSTM1 is ubiquitinated by NEDD4 while LC3 functions as an activator of NEDD4 ligase activity. | SIGNOR-278637 |
P27361 | Q02750 | 0 | phosphorylation | up-regulates | 0.752 | Mek1 as indicated by extensive phosphorylation of erk1 and erk2 during the initial 2 h of adipogenesis. | SIGNOR-210176 |
P12755 | O14965 | 0 | phosphorylation | down-regulates quantity by destabilization | 0.2 | Here we show that AURKA phosphorylates in vitro the transcripcional co-repressor Ski on aminoacids Ser326 and Ser383. Phosphorylations on these aminoacids decreased Ski protein half-life | SIGNOR-276917 |
P33981 | P27816 | 1 | phosphorylation | down-regulates quantity by destabilization | 0.2 | We further uncovered that Mps1 is a kinase of MAP4, and E7-MAP4 binding blocks Mps1 phosphorylation of MAP4, thereby interrupting phosphorylation-dependent MAP4 degradation. | SIGNOR-277458 |
Q86Y13 | P20671 | 1 | monoubiquitination | up-regulates activity | 0.2 | 2A-HUB catalyzes monoubiquitination of H2A at lysine 119, functioning as a combinatoric component of the repression machinery required for specific gene regulation programs. Thus, 2A-HUB mediates a selective repression of a specific set of chemokine genes in macrophages, critically modulating migratory responses to TLR activation. H2A monoubiquitination acts to prevent FACT recruitment at the transcriptional promoter region, blocking RNA polymerase II release at the early stage of elongation. | SIGNOR-271753 |
P24941 | P09874 | 1 | phosphorylation | up-regulates activity | 0.358 | CDK2 dependent activation of PARP-1 is required for hormonal gene regulation in breast cancer cells.|Hormone dependent phosphorylation of PARP-1 by CDK2, within the catalytic domain, enhances its enzymatic capabilities. | SIGNOR-279146 |
P09488 | P10242 | 0 | transcriptional regulation | up-regulates quantity by expression | 0.2 | Functional analysis of the GSTM1 promoter using reporter assays indicated that both the DNA binding and transactivation domains of Myb were required for transcriptional activation | SIGNOR-253975 |
Q9BRS2 | P68400 | 0 | phosphorylation | up-regulates quantity by stabilization | 0.332 | Casein kinase 2 (CK2) phosphorylates RIOK1 at T410, which stabilizes RIOK1 by antagonizing K411 methylation and impeding the recruitment of FBXO6 to RIOK1. | SIGNOR-273630 |
O00187 | P0C0L5 | 1 | cleavage | up-regulates activity | 0.798 | MASP-2 cleaves C4 releasing C4a and generating C4b, which attaches covalently to the pathogen surface upon exposure of its reactive thioester. C2 binds to C4b and is also cleaved by MASP-2 to form the C3 convertase (C4b2a). | SIGNOR-263422 |
Q9Y3I1 | O43379 | 1 | ubiquitination | down-regulates quantity by destabilization | 0.2 | WDR62 is also negatively regulated by T1053 phosphorylation, leading to the recruitment of F-box and WD repeat domain-containing protein 7 (FBW7) and proteasomal degradation. |JNK1 can induce the phosphorylation of WDR62 T1053 | SIGNOR-271711 |
Q00535 | Q8IV63 | 1 | phosphorylation | up-regulates activity | 0.356 | Vaccinia-related kinase 3 (VRK3), a member of the VRK family, is widely expressed in human tissues and increases VHR phosphatase activity through a direct binding|Here we report that oxidative stress-induced cyclin-dependent kinase 5 (CDK5) activation stimulates neuroprotective signaling via phosphorylation of vaccinia-related kinase 3 (VRK3) at Ser 108. The binding of vaccinia H1-related (VHR) phosphatase to phosphorylated VRK3 increased its affinity for phospho-ERK and subsequently downregulated ERK activation| | SIGNOR-275544 |
Q12772 | Q14534 | 1 | transcriptional regulation | up-regulates quantity by expression | 0.595 | The processed SREBP2, designated nuclear SREBP2 (nSREBP2), then enters the nucleus as a homodimer, binds to the sterol regulatory element (SRE) sequence in the promoters of target genes, including HMGCR and SQLE (encoding squalene monooxygenase), and upregulates their transcription | SIGNOR-265162 |
Q14247 | P28482 | 0 | phosphorylation | up-regulates | 0.467 | Cortactin is regulated by multiple phosphorylation events, including phosphorylation of s405 and s418 by extracellular regulated kinases (erk)1/2. Erk1/2 phosphorylation of cortactin has emerged as an important positive regulatory modification, enabling cortactin to bind and activate the arp2/3 regulator neuronal wiskott-aldrich syndrome protein (n-wasp), promoting actin polymerization and enhancing tumor cell movement. | SIGNOR-165200 |
Q6WCQ1 | Q13546 | 0 | phosphorylation | up-regulates activity | 0.2 | Under such conditions, RIP1 phosphorylates and activates RIP3, which in turn phosphorylates its downstream substrate MLKL, leading to plasma membrane rupture and necrosis( xref ). | SIGNOR-279755 |
Q86V86 | P61073 | 1 | phosphorylation | up-regulates quantity | 0.263 | Pim-1 and Pim-3 enhance phosphorylation and cell surface expression of CXCR4.|The intracellular tail of CXCR4 can be phosphorylated in vitro at Ser339 by Pim-1 kinase and by Pim-3, as shown here, but not by Pim-2. | SIGNOR-279092 |
P09086 | P07947 | 0 | phosphorylation | up-regulates activity | 0.2 | These data suggest that Yes1 is the TKI-sensitive kinase that can directly phosphorylate OCT2. | SIGNOR-279664 |
P23677 | P17612 | 0 | phosphorylation | up-regulates activity | 0.327 | Two isoforms of the inositol 1,4,5-trisphosphate 3-kinase have been identified, the A form and the B form. phosphorylation of isoform A by the cyclic AMP-dependent protein kinase increased activity 1.5-fold, whereas phosphorylation of isoform B decreased activity by 45%. major phosphorylation sites in the protein are Ser119 for PKA. Ser119 in the A isoform is conserved in the B isoform as Ser328 | SIGNOR-249994 |
O14737 | P68400 | 0 | phosphorylation | up-regulates | 0.2 | Programmed cell death 5 (pdcd5), a protein involved in cell death and down-regulated in different forms of human tumors. Pdcd5 is phosphorylated in vitro by both ck2alpha subunit and by the ck2 holoenzyme at a residue, s118, which is found phosphorylated in vivo. Transfection of the non-phosphorylatable mutant (s118a) impairs the pdcd5 acceleration of either doxorubimicin- or uv-induced apoptosis in u2os cells | SIGNOR-187106 |
P12931 | P13688 | 1 | phosphorylation | up-regulates activity | 0.426 | Recent reports have also suggested that Bgp1 behaves as a signal transduction molecule. Several physiological events promote the Tyr phosphorylation of Bgp1 on one or two Tyr residues within its cytoplasmic domain (Tyr-488 and Tyr-515). BGP becomes Tyr-phosphorylated by Src-like Tyr kinases in activated neutrophils (24) and in human colon carcinoma cellsWe have recently shown that Tyr phosphorylation of the mouse Bgp1 cytoplasmic domain in CT51 mouse colonic carcinoma cells led to its binding to the protein-Tyr phosphatase SHP-1 and that this event required the presence of both Tyr-488 and Tyr-515 | SIGNOR-246471 |
O00712 | Q9HD90 | 1 | transcriptional regulation | up-regulates quantity | 0.2 | For example, within the NFI targetome, we identified 6 collagen genes, 13 genes encoding potassium channel or glutamate receptor subunits and a range of factors related to axon guidance (e.g. Slit1, Robo1, Epha4, Epha5, Epha8) | SIGNOR-268898 |
P35916 | P51812 | 1 | phosphorylation | down-regulates | 0.2 | Upon truncation of this c-terminal stretch, or mutation of the tyr-707 residue alone, autoinhibition is attenuated, and the kinase becomes constitutively active. Based on these findings we propose that phosphorylation of the tyr-707 represents a novel alternative regulatory mechanism for p90rsk activation. | SIGNOR-98708 |
P53004 | P06213 | 0 | phosphorylation | up-regulates activity | 0.479 | Human BVR (hBVR) also reduces the hemeoxygenase activity product biliverdin to bilirubin and is directly activated by insulin receptor kinase (IRK).|in addition to Y198 in the YMKM motif, 2 other tyrosines, Y228 in the YLSF motif and Y291 in the C-terminus of the protein, are directly phosphorylated by IRK | SIGNOR-275514 |
O14807 | P49356 | 0 | null | up-regulates activity | 0.273 | Major investments have been made to target Ras through indirect routes. Inhibition of farnesyl transferase to block Ras maturation has failed in large clinical trials. | SIGNOR-242562 |
P68400 | Q96NY9 | 1 | phosphorylation | up-regulates activity | 0.2 | Here, we show that the CK2 kinase phosphorylates MUS81 at Serine 87 in late-G2/mitosis, and upon mild replication stress. Phosphorylated MUS81 interacts with SLX4, and this association promotes the function of the MUS81 complex. | SIGNOR-273626 |
Q96GD4 | P84243 | 1 | phosphorylation | up-regulates activity | 0.2 | Phosphorylation at ser-11 (h3s10ph) by aurkb is crucial for chromosome condensation and cell-cycle progression during mitosis and meiosis. Phosphorylation at ser-11 (h3s10ph) by aurkb is crucial for chromosome condensation and cell-cycle progression during mitosis and meiosis. | SIGNOR-118890 |
O00401 | P17706 | 0 | dephosphorylation | down-regulates | 0.29 | Similarly, the t cell phosphatase has a 30-fold lower kcat/km toward autoinhibited p-n-wasp than toward the isolated p-gbd, and again this effect is largely reversed by that cdc42 | SIGNOR-141652 |
P08581 | Q12913 | 0 | dephosphorylation | down-regulates activity | 0.608 | When co-expressed in 293 cells, the full-length substrate-trapping mutant form of DEP-1 formed a stable complex with the chimeric receptor colony stimulating factor 1 (CSF)-Met and wild type DEP-1 dephosphorylated CSF-Met. Furthermore, we observed that DEP-1 preferentially dephosphorylated a Gab1 binding site (Tyr(1349)) and a COOH-terminal tyrosine implicated in morphogenesis (Tyr(1365)), | SIGNOR-248702 |
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