GleghornLab/Signor_3class · Datasets at Hugging Face

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
Q9NZS9	P55061	1	polyubiquitination	down-regulates quantity by destabilization	0.392	BAR overexpression promotes BI-1 ubiquitination and proteasomal degradation.We show here that bifunctional apoptosis regulator (BAR) functions as an ER-associated RING-type E3 ligase, interacts with BI-1, and promotes proteasomal degradation of BI-1.	SIGNOR-272778
K9N643	Q14164	2	binding	down-regulates activity	0.2	Previous studies have shown that MERS-CoV ORF4b antagonizes the early antiviral alpha/beta interferon (IFN-α/β) response, which may significantly contribute to MERS-CoV pathogenesis; however, the underlying mechanism is poorly understood. Here, we found that ORF4b in the cytoplasm could specifically bind to TANK binding kinase 1 (TBK1) and IκB kinase epsilon (IKKε), suppress the molecular interaction between mitochondrial antiviral signaling protein (MAVS) and IKKε, and inhibit IFN regulatory factor 3 (IRF3) phosphorylation and subsequent IFN-β production. these results indicate that MERS-CoV ORF4b inhibits the induction of type I IFN through a direct interaction with IKKε/TBK1 in the cytoplasm	SIGNOR-260592
P49757	P08151	2	binding	down-regulates	0.623	The consequent activation of_ itch, together with the recruitment of gli1 through direct binding with_ numb, allows gli1 to enter into the complex, resulting in gli1 ubiquitination and degradation.	SIGNOR-167841
Q53ET0	P35558	1	transcriptional regulation	up-regulates quantity	0.386	These results reveal that CRTC2 plays an essential role in the regulation of hepatic gluconeogenesis through coordinated regulation of the glucocorticoid/GR- and glucagon/CREB-signaling pathways on the key genes G6P and PEPCK.	SIGNOR-256106
P35221	P12830	2	binding	up-regulates	0.686	Additionally, the E-cadherin associated protein _-catenin regulates YAP directly by sequestering YAP/14-3-3 complexes in the cytoplasm.	SIGNOR-203468
P28482	P00533	1	phosphorylation	down-regulates activity	0.639	A growth factor-stimulated protein kinase activity that phosphorylates the epidermal growth factor (EGF) receptor at Thr669 has been described Anion-exchange chromatography demonstrated that this protein kinase activity was accounted for by two enzymes. The first peak of activity eluted from the column corresponded to the microtubule-associated protein 2 (MAP2) kinase	SIGNOR-20545
P17612	Q9NR82	1	phosphorylation	up-regulates activity	0.2	We conclude that phosphorylation of S53 on the amino terminus of Kv7.5 is essential for PKA-dependent enhancement of channel activity in response to βAR activation in vascular and airway smooth muscle cells.	SIGNOR-265980
P09017	O15550	0	transcriptional regulation	up-regulates quantity by expression	0.467	Evidence for direct involvement of UTX in regulation of HOX gene activity was demonstrated through UTX knockdown experiments in HEK293T cells in which loss of UTX induced transcriptional repression of HOXA and HOXC clusters.	SIGNOR-260030
O75581	P04628	2	binding	up-regulates activity	0.828	Ligands such as wnt1, wnt3a, and wnt8 couple the seventransmembrane domain receptor frizzled (fzd) and the single-membrane-spanning low-density receptor-related protein 5/6 (lrp5/6) to activate wnt?Beta-catenin signaling.	SIGNOR-169648
P35236	Q02156	0	phosphorylation	up-regulates activity	0.2	HePTP is phosphorylated by PKC isozymes at Ser-225 in vitro. While all isozymes phosphorylated Ser-225 predominantly and Ser-113 to a lesser extent (Fig. (Fig.5),5), they differed strikingly in how much 32P they incorporated into HePTP during the 30-min assay. PKC θ was the most efficient, while PKC ζ and PKC μ were clearly less potent; PKC δ, ɛ, and η were quite inefficient.	SIGNOR-276050
Q9NT99	P78352	2	binding	up-regulates activity	0.37	A possible function for the NGL–PSD-95 interaction is to couple trans-synaptic adhesion events to the recruitment of PSD-95 and other PSD-95-associated postsynaptic proteins. PSD-95 and liprin-α may be key synaptic scaffolding proteins that couple trans-synaptic adhesions to the assembly of synaptic proteins/vesicles	SIGNOR-264052
P23467	P06213	1	dephosphorylation	down-regulates	0.344	Identification of tyrosine phosphatases that dephosphorylate the insulin receptor.	SIGNOR-75997
P17676	P28845	1	transcriptional regulation	up-regulates quantity by expression	0.284	In conclusion, C/EBPalpha and C/EBPbeta control basal transcription, and TNF-alpha upregulates 11beta-HSD1, most likely by p38 MAPK-mediated increased binding of C/EBPbeta to the human HSD11B1 promoter.	SIGNOR-268972
O00451	P39905	2	binding	up-regulates	0.673	Gdnf mediates its actions through a multicomponent receptor system composed of a ligand-binding glycosyl-phosphatidylinositol (gpi)-linked protein (designated gdnfr-alpha).	SIGNOR-49184
Q8NEB9	P12931	0	phosphorylation	up-regulates activity	0.42	Given that VPS34 is activated by Src mediated tyrosine phosphorylation, we next determined if VPS34 was tyrosine phosphorylated following insulin treatment.\|These data indicate that VPS34 is an effector of insulin-mediated signal transduction and that Src phosphorylation of VPS34 is required for this function.	SIGNOR-278456
Q13315	Q9Y297	1	phosphorylation	up-regulates quantity by stabilization	0.299	ATM phosphorylates and stabilizes β-TrCP1 upon DNA damage.	SIGNOR-277549
Q13541	P49841	0	phosphorylation	down-regulates activity	0.364	We found that gsk-3Beta phosphorylates and inactivates 4e-bp1, thereby increasing eif4e-dependent protein synthesis. upon stimulation, 4e-bp1 is phosphorylated on several threonine and serine residues, including thr-37/46 (36). This results in dissolution of the complex, freeing eif4e to bind with mrna cap to promote translation initiation.	SIGNOR-236026
P26927	P03952	0	cleavage	up-regulates activity	0.325	Proteolytic cleavage of pro-MSP at a single site yields active MSP, a disulfide-linked alphabeta-chain heterodimer. human kallikrein cleaved only at Arg483–Val484, the cleavage site for formation of a- and b-chains.	SIGNOR-256511
P46937	Q01538	0	transcriptional regulation	down-regulates quantity by repression	0.2	Myt1 and Myt1l transcription factors limit proliferation in GBM cells by repressing YAP1 expression. Examination of the gene expression changes in cells expressing Myt1 or Myt1l suggests that both repress expression of the YAP1 transcriptional coactivator, which functions primarily in the Hippo signaling pathway. Expression of YAP1 and its target genes is reduced in Myt-expressing cells, and there is an inverse correlation between YAP1 and MYT1/MYT1L expression in human brain cancer datasets. Together, our data suggest that Myt1 and Myt1l directly repress expression of YAP1, a protein which promotes proliferation and GBM growth.	SIGNOR-266777
O95352	P60520	2	binding	up-regulates activity	0.905	Three human atg8 (hatg8) homologs, lc3, gabarap, and gate-16, have been characterized as modifiers in reactions mediated by hatg7 (an e1-like enzyme) and hatg3 (an e2-like enzyme).	SIGNOR-142002
O15492	P00533	0	phosphorylation	up-regulates	0.415	Phosphorylation on tyr(168) was mediated by the epidermal growth factor receptor (egfr). We show here that endogenous rgs16 is phosphorylated after epidermal growth factor stimulation of mcf-7 cells.	SIGNOR-98267
P25098	P30411	1	phosphorylation	down-regulates activity	0.2	Ligand-induced phosphorylation is found at Ser339 and Ser346/Ser348 that could be executed by several G protein-coupled receptor kinases. 32P labeling of peptide 3 containing pS346/pS348 was enhanced 1.5–3-fold as compared with mock-transfected cells in the order GRK6 < GRK5 < GRK2 < GRK4α < GRK3. several endogenous GRKs may phosphorylate the B2R and that the various GRKs, even without apparent effect on total GPCR phosphorylation levels, may induce distinct phosphorylation patterns with possible functional consequences for receptor desensitization and sequestration.	SIGNOR-251445
O60260	P27695	1	ubiquitination	down-regulates quantity by destabilization	0.2	Based on these results, we conclude that Parkin directly ubiquitinates APE1.\|These results indicated that degradation of APE1 by Parkin was limited compared to the transiently expressed APE1, suggesting that a large portion of APE1 is not in contact with the Parkin and PINK1 without induction of stresses such as oxidative stress.	SIGNOR-278531
Q9NRL3	Q9P2B4	2	binding	up-regulates activity	0.666	Although CTTNBP2 and CTTNBP2NL are different in terms of tissue and subcellular distribution, our data indicate that, similar to CTTNBP2NL, CTTNBP2 associates with members of the striatin family, namely striatin and zinedin. Moreover, CTTNBP2 is critical for the distribution of striatin and zinedin in dendritic spines. The role of CTTNBP2 in the regulation of the synaptic distribution of striatin and zinedin suggests that CTTNBP2 regulates synaptic signaling through PP2A.	SIGNOR-261701
Q96J92	P12931	0	phosphorylation	down-regulates activity	0.2	Using Western blot and mass spectrometry, we now identify three sites in WNK4 that are phosphorylated by c-Src: Tyr(1092), Tyr(1094), and Tyr(1143), and show that both c-Src and protein tyrosine phosphatase type 1D (PTP-1D) coimmunoprecipitate with WNK4.	SIGNOR-276897
Q15185	P68400	0	phosphorylation	up-regulates	0.354	Several lines of evidence suggest that a cpges-activating protein kinase is ck-ii (casein kinase ii). Recombinant cpges was phosphorylated directly by and associated with ck-ii in vitro, resulting in marked reduction of the k m for the substrate pgh2.	SIGNOR-123594
P63096	Q92633	2	binding	up-regulates activity	0.555	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-256696
P10909	O14920	2	binding	down-regulates quantity by destabilization	0.2	CLU-2 is a ubiquitin binding protein (UBP) that enhances proteasome activity. sCLU promotes degradation of COMMD1. sCLU interacts with the SCF-βTrCP E3 ligase complex, serving as a scaffolding chaperone to form a multimeric protein complex that facilitates COMMD1 and I-κB ubiquitination and proteasomal degradation.	SIGNOR-271433
P68431	Q92830	0	acetylation	down-regulates activity	0.2	The HAT module within the SAGA and ADA complexes acetylates histone H3, mainly on residues K9 and K14.	SIGNOR-269602
Q9BY84	Q9UQF2	2	binding	up-regulates	0.44	Here we report that jip-1 also binds the dual-specificity phosphatases mkp7 and m3/6 via a region independent of its jnk binding domain. when mkp7 is bound to jip-1 it reduces jnk activation leading to reduced phosphorylation of the jnk target c-jun	SIGNOR-97173
Q01484	Q9UJW0	1	relocalization	up-regulates quantity	0.625	We present evidence for an ankyrin-based mechanism for sarcolemmal localization of dystrophin and beta-DG. Ankyrin-B thus is an adaptor required for sarcolemmal localization of dystrophin, as well as dynactin-4.	SIGNOR-266713
P04150	P53041	0	dephosphorylation	down-regulates activity	0.541	Estrogen inhibits glucocorticoid action via protein phosphatase 5 (PP5)-mediated glucocorticoid receptor dephosphorylation.\|Inhibition of GR phosphorylation at Ser-211 is associated with decreased nuclear retention of GR and decreased gene transcription.	SIGNOR-248538
P55212	P42574	0	cleavage	up-regulates	0.619	Caspase-3 is required for the activation of caspases 6	SIGNOR-64179
P78362	P48729	0	phosphorylation	up-regulates activity	0.25	Here, we demonstrate that mTORC1 promotes lipid biogenesis via SRPK2, a key regulator of RNA-binding SR proteins. mTORC1-activated S6K1 phosphorylates SRPK2 at Ser494, which primes Ser497 phosphorylation by CK1. These phosphorylation events promote SRPK2 nuclear translocation and phosphorylation of SR proteins.	SIGNOR-275460
P37173	P61812	2	binding	up-regulates	0.754	We show that tbetarii-b, an alternatively spliced variant of the tgf-beta type ii receptor, is a tgf-beta2 binding receptor, which mediates signalling via the smad pathway in the absence of any tgf-beta type iii receptor	SIGNOR-104795
O95999	O76064	0	ubiquitination	up-regulates quantity by stabilization	0.328	Phosphorylated and ubiquitinated BCL10 is stabilized on the damage sites through binding to and presenting UBC13 to RNF168.\|We thus concluded that BCL10 is ubiquitinated mainly with K63-linked ubiquitination by RNF8.	SIGNOR-278778
P61587	Q13464	0	phosphorylation	up-regulates	0.707	We show that rock phosphorylates endogenous rhoe at serine 11 upon cell stimulation with platelet-derived growth factor. Phosphorylation has no effect on rhoe binding to rock i, but instead increases rhoe protein stability.	SIGNOR-134703
P10275	O15164	2	binding	up-regulates	0.396	We found that trim24/transcriptional intermediary factor 1alpha (tif1alpha), which is known as a ligand-dependent nuclear receptor co-regulator, interacts with ar and enhances transcriptional activity of ar	SIGNOR-189113
P24752	P11362	0	phosphorylation	up-regulates activity	0.2	Treatment with the FGFR1 inhibitor TKI258 in FGFR1-expressing H1299 cells led to decreased Y407 phosphorylation of ACAT1 in the mitochondrial fraction, where both ACAT1 and a fraction of FGFR1 were detected\|Inhibition of tetrameric ACAT1 by abolishing Y407 phosphorylation or AH treatment results in decreased ACAT1 activity,	SIGNOR-264423
Q13557	Q9UQD0	1	phosphorylation	up-regulates activity	0.281	CaMKII enhances voltage-gated sodium channel Nav1.6 activity and neuronal excitability\|mmobilized peptide arrays and nanoflow LC-electrospray ionization/MS of Nav1.6 reveal potential sites of CaMKII phosphorylation, specifically Ser-561 and Ser-641/Thr-642 within the first intracellular loop of the channel.	SIGNOR-275792
Q13635	Q99835	2	binding	down-regulates activity	0.786	We show that free Ptc (unbound by Hh) acts sub-stoichiometrically to suppress Smo activity and thus is critical in specifying the level of pathway activity.	SIGNOR-91709
O15169	P62140	0	dephosphorylation	down-regulates activity	0.2	The data suggest that PP1 controls Wnt signaling through interaction with, and regulated dephosphorylation of, axin\| Axin phosphorylation markedly enhances the binding of glycogen synthase kinase 3, leading to a more active beta-catenin destruction complex. Wnt-regulated changes in axin phosphorylation, mediated by PP1, may therefore determine beta-catenin transcriptional activity\| Four sites, S80, S82, S222, and S473, were identified to be PP1 regulated	SIGNOR-248567
P21728	O95837	2	binding	up-regulates activity	0.265	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-257391
P14618	P24666	0	dephosphorylation	up-regulates activity	0.279	Indeed, it is evident that LMW-PTP, hydrolyzing phosphotyrosine residues, contributes to maintain PKM2 in its active form.\|We speculate that this effect is in large part due to LMW-PTP inhibition, which leads a fast PKM2 phosphorylation and inactivation.\|we demonstrate that in melanoma cells the overexpression of LMW-PTP is functional to maintain PKM2 in its dephosphorylate status – the tetrameric, “full active” form - which is retained in the cytoplasm	SIGNOR-277134
Q92997	Q92945	2	binding	down-regulates	0.2	Ksrp was shown to interact with the c-terminus of dvl3. We show that ksrp negatively regulates wnt/beta-catenin signaling at the level of post-transcriptional ctnnb1 (beta-catenin) mrna stability.	SIGNOR-23800
P19174	Q07889	2	binding	up-regulates	0.647	We provide evidence that sos1, a p21ras-specific guanine nucleotide exchange factor, directly binds to the sh3 domain of plc-gamma1, and that the sh3 domain of plc-gamma1 is involved in sos1-mediated p21ras activation.	SIGNOR-80024
P15941	P00533	0	phosphorylation	up-regulates activity	0.577	We also show that the activated egf-r phosphorylates the muc1 cytoplasmic tail on tyrosine at a yekv motif that functions as a binding site for the c-src sh2 domain. The results demonstrate that egf-r-mediated phosphorylation of muc1 induces binding of muc1 to c-src in cells	SIGNOR-109538
Q13464	O14974	1	phosphorylation	down-regulates activity	0.774	Phosphorylation by Rho-kinase inhibited MP activity and this reflected a decrease in V(max). Activity of MP with different substrates also was inhibited by phosphorylation. Two major sites of phosphorylation on MYPT1 were Thr(695) and Thr(850).	SIGNOR-249034
P35348	P63092	2	binding	up-regulates activity	0.291	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 ‚â• -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 ‚â• -1.0 for defining true couplings. \| The score associated to this interaction has a LogRAi ‚â• -1.0.	SIGNOR-256812
P01112	P20936	2	binding	down-regulates	0.848	The Ras protein sits at the center of a many-tiered cascade of molecular interactions. Most of the proteins along this cascade are activated by phosphorylation, but Ras uses a bound guanine nucleotide to toggle between its on and off states. Ras hydrolyzes GTP to GDP fairly quickly, turning itself off, and a collection of GTPase-activating proteins (GAPs) speed up the processthe complex between human h-ras bound to guanosine diphosphate and the guanosine triphosphatase (gtpase)-activating domain of the human gtpase-activating protein p120gap (gap-334) in the presence of aluminum fluoride was solved.	SIGNOR-68990
Q06609	P42229	0	transcriptional regulation	up-regulates quantity by expression	0.263	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-261552
Q9BW19	P06493	0	phosphorylation	up-regulates quantity by stabilization	0.458	We confirmed that CDK1 phosphorylates Ser6 (Supplementary Fig S5B) and demonstrated that KIFC1 displays CDK1-mediated resistance to ubiquitination by the APC/C (Fig S5C).	SIGNOR-277294
P15498	O15524	2	binding	down-regulates quantity by destabilization	0.598	SOCS1 stimulates the polyubiquitination of VAV proteins in vivo, which was stabilized by proteasomal inhibitors. These results suggest that SOCS1 programs VAV degradation by acting as a substrate-specific recognition component of a VCB-like ubiquitin ligase complex.	SIGNOR-272559
P22460	Q13131	0	phosphorylation	down-regulates activity	0.2	Thus, AMPK directly phosphorylates the  subunit of KV1.5 at Ser592 and, to a lesser extent, at Ser560	SIGNOR-277814
Q7RTT9	P19544	0	transcriptional regulation	up-regulates quantity by expression	0.274	ENT4 is transcriptionally activated by both isoforms of EWS/WT1 as evidenced by promoter-reporter and chromatin immunoprecipitation (ChIP) analyses.	SIGNOR-268985
P45983	Q9UPT6	2	phosphorylation	up-regulates	0.722	Phosphoamino acid analysis confirmed that jnk caused thr phosphorylation of jip3 (fig. _(fig.3c).3c). This phosphorylation on thr was markedly decreased when thr266, thr276, and thr287 were replaced with ala. These data indicate that jnk phosphorylated jip3 on thr266, thr276, and thr287 in vitro.	SIGNOR-134545
Q9HAU4	Q15797	1	polyubiquitination	down-regulates quantity by destabilization	0.725	Here, we report the identification of Smurf2, a new member of the Hect family of E3 ubiquitin ligases. Smurf2 selectively interacts with receptor-regulated Smads and preferentially targets Smad1 for ubiquitination and proteasome-mediated degradation. At higher expression levels, Smurf2 also decreases the protein levels of Smad2, but not Smad3.	SIGNOR-272936
O14867	P52789	1	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
P35626	P51681	1	phosphorylation	down-regulates activity	0.2	Serine residues at positions 336, 337, 342, and 349 represent GRK phosphorylation sites on CCR5. CCR5 phosphorylation and desensitization through a GRK-mediated mechanism	SIGNOR-251463
P51948	P03372	1	phosphorylation	up-regulates activity	0.397	Human Estrogen Receptor α Is Phosphorylated at Serine 118 In Vivo by Cdk7	SIGNOR-260837
Q9UKC9	Q96P20	2	binding	down-regulates quantity by destabilization	0.351	LPS exposure reduces the ubiquitin-mediated proteasomal processing of NALP3 by inducing levels of an E3 ligase component, FBXO3, which targets FBXL2. The latter is an endogenous mediator of NALP3 degradation. FBXL2 recognizes Trp-73 within NALP3 for interaction and targets Lys-689 within NALP3 for ubiquitin ligation and degradation.	SIGNOR-272432
O14976	P12931	0	phosphorylation	up-regulates activity	0.274	GAK is phosphorylated by c-Src and translocated from the centrosome to chromatin at the end of telophase. Cyclin G-associated kinase (GAK) harbors a consensus phosphorylation motif (Y412) for c-Src; however, its physiological significance remains elusive. Here, we show that GAK is phosphorylated by c-Src not only at Y412 but also at Y1149.	SIGNOR-263197
Q06124	P40763	1	dephosphorylation	down-regulates activity	0.77	In addition, SHP-2 dephosphorylates tyrosine-phosphorylated Stat1/3/5A (Ohtani et al., 2000; Wu et al., 2002; Chen et al., 2003), and downregulates Stat3-mediated biological actions (Ohtani et al., 2000).\|Inhibition of collagen-induced Stat3 tyrosine-705 (Stat3-p-Tyr)	SIGNOR-272404
P68400	P55957	1	phosphorylation	up-regulates activity	0.286	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-250831
P10398	Q8IVT5	2	binding	up-regulates activity	0.567	In mammals, RAF family kinases include three catalytically competent enzymes (ARAF, BRAF and CRAF) and two pseudokinases (KSR1 and KSR2) that have been described as scaffolds owing to their apparent ability to bridge RAF isoforms and their substrate, mitogen-activated protein kinase kinase (MEK).Kinase suppressor of Ras (KSR) pseudokinases were also shown to dimerize with kinase-competent RAFs to stimulate catalysis allosterically.	SIGNOR-273876
O15393	P0DTC2	1	cleavage	up-regulates activity	0.2	Here, we demonstrate that SARS-CoV-2 uses the SARS-CoV receptor ACE2 for entry and the serine protease TMPRSS2 for S protein priming. The Cellular Serine Protease TMPRSS2 Primes SARS-2- S for Entry, and a Serine Protease Inhibitor Blocks SARS-CoV-2 Infection of Lung Cells	SIGNOR-260736
P0C1S8	P06493	1	phosphorylation	down-regulates activity	0.587	Recombinant Wee1B effectively phosphorylated cyclin B-associated Cdk1 on tyrosine-15, resulting in an inactivation of the kinase activity of Cdk1.	SIGNOR-279134
P45984	P15336	1	phosphorylation	up-regulates	0.698	Phosphorylation of thr-69 by mapk14 and mapk11, and at thr-71 by mapk1/erk2, mapk3/erk1, mapk11, mapk12 and mapk14 in response to external stimulus like insulin causes increased transcriptional activity.	SIGNOR-163266
Q9NS23	Q96GD4	0	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
Q13164	Q16828	0	dephosphorylation	down-regulates activity	0.646	However, whilst the interaction itself might be difficult to monitor, DUSP6 should still be able to promote the de-phosphorylation of ERK5 in cells if it is an ERK5 phosphatase.To test this HEK293 cells were transiently transfected with HA-ERK2 or HA-ERK5 together with EGFP-MEK1E (a constitutively active version of MEK1) or EGFP-MEK5D (a constitutively active version of MEK5).\|Whilst one can envisage scenarios in which the interaction between DUSPs and their substrates might be transient, DUSP6 should still be able to promote the de-phosphorylation and inactivation of ERK5.	SIGNOR-277007
Q99683	P52564	1	phosphorylation	up-regulates activity	0.613	A MAP kinase kinase kinase (MAPKKK), termed ASK1, was identified that activated two different subgroups of MAP kinase kinases (MAPKK), SEK1 (or MKK4) and MKK3/MAPKK6 (or MKK6), which in turn activated stress-activated protein kinase (SAPK, also known as JNK; c-Jun amino-terminal kinase) and p38 subgroups of MAP kinases, respectively.	SIGNOR-45353
P54619	P54646	2	binding	up-regulates	0.897	Gamma non-catalytic subunit mediates binding to amp, adp and atp, leading to activate or inhibit ampk: amp-binding results in allosteric activation of alpha catalytic subunit (prkaa1 or prkaa2) both by inducing phosphorylation and preventing dephosphorylation of catalytic subunits.	SIGNOR-139173
P50148	P61586	2	binding	up-regulates	0.576	Recently, the dbl-family guanine nucleotide exchange factor (gef) p63rhogef/geft has been described as a novel mediator of galpha(q/11) signaling to rhoa based on its ability to synergize with galpha(q/11) resulting in enhanced rhoa signaling in cells.	SIGNOR-156534
P62805	O94874	0	ubiquitination	up-regulates activity	0.2	Here we report that UFM1 specific ligase 1 (UFL1), an ufmylation E3 ligase, is important for ATM activation.	SIGNOR-265072
Q5SGD2	O43318	1	dephosphorylation	down-regulates activity	0.585	Co-immunoprecipitation experiments indicated that PP2Cepsilon associates stably with TAK1 and attenuates the binding of TAK1 to MKK4 or MKK6.\|PP2Cepsilon dephosphorylated TAK1 in vitro.	SIGNOR-277114
P43405	Q8IWV1	1	phosphorylation	up-regulates activity	0.378	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-273535
Q6P589	O43318	0	phosphorylation	down-regulates quantity by destabilization	0.2	TAK1 phosphorylated the Ser3 in the noncanonical degron motif of TIPE2 to trigger its interaction with β-TrCP for subsequent ubiquitination and degradation.	SIGNOR-273668
P05771	Q05639	1	phosphorylation	up-regulates activity	0.2	PKCβI phosphorylates eEF1A at Ser53.our proteomics exploration of cPKC signaling in the nuclei of C2C12 cells demonstrated that the up-regulation of eEF1A intranuclear content, evoked by insulin, is associated with an increase in the phosphorylation of the Ser53 residue of the protein.	SIGNOR-263166
P27361	P15056	1	phosphorylation	down-regulates	0.645	Erk-induced phosphorylation of b-raf on t753 promoted the disassembly of raf heterodimers, and the mutation of t753 prolonged growth factor-induced heterodimerization. The b-raf t753a mutant enhanced differentiation of pc12 cells, which was previously shown to be dependent on sustained erk signaling. Site is critical for v-src dependent modulation of slk kinase activity.	SIGNOR-144827
O43597	P12931	0	phosphorylation	up-regulates	0.565	Activation of signalling by fibroblast growth factor receptor leads to phosphorylation of the signalling attenuator human sprouty 2 (hspry2) on residue y55. we show that hspry2 is a direct substrate for src family kinases, including src itself.Phosphorylation of hspry2 is required for hspry2 to inhibit activation of the extracellular signal-regulated kinase pathway.	SIGNOR-131189
P06730	Q13490	0	ubiquitination	down-regulates quantity by destabilization	0.401	We found that endogenous eIF4E was ubiquitinated by cIAP1, and ubiquitinated eIF4E accumulated upon MG132 treatment.	SIGNOR-278741
Q92830	P11802	0	phosphorylation	up-regulates activity	0.36	Activated cyclin D1-Cdk4 kinase phosphorylates and activates GCN5\|GCN5 T272A/S372A (AA) phosphorylation by cyclin D1-CDK4 kinase is diminished compared to GCN5 wild-type (WT)	SIGNOR-275494
P02452	P13497	0	cleavage	up-regulates activity	0.681	BMP-1myc Expressed in COS-7 Cells Exhibits Procollagen C-proteinase Activity. Bone morphogenetic protein (BMP)-1, which belongs to the tolloid subgroup of astacin-like zinc metalloproteinases, cleaves the C-propeptides of procollagen at the physiologic site and is, therefore, a procollagen C-proteinase (PCP). Cleavage occurs between a specific alanine or glycine residue (depending on the procollagen chain) and an invariant aspartic acid residue in each of the three chains of procollagen.	SIGNOR-256342
O14640	O60353	2	binding	up-regulates activity	0.678	When canonical wnts bind to their respective fzd receptors, heterotrimeric g-proteins and dsh get activated and lead to the recruitment of axin to the fzd co-receptor lrp.	SIGNOR-198828
P0C0L5	Q96PZ7	2	binding	down-regulates quantity	0.2	CUB and sushi multiple domains 1 (CSMD1) is a relatively poorly studied large transmembrane protein of 390 kDa composed of 14 N-terminal CUB domains interspersed with complement control protein (CCP) domains followed by 15 consecutive CCP domains. The active domains of CSMD1 were then identified in CCP17-21, which were shown to interact with C4b and C3b and present these complement proteins for degradation by factor	SIGNOR-265149
P23458	P16871	2	binding	up-regulates	0.638	For instance, jak1 is associated with the ? Subunits of ?c Cytokines such as il-7r? And IL-4R. jak3 is associated with the ?c20,21. Cytokine binding mediates the trans-phosphorylation of receptor associated jak kinases, which in turn phosphorylate tyrosine residues on the receptors themselves. The receptor phosphotyrosines serve as docking sites for sh2 domain proteins including the stat family of transcription factors which are activated by jak-mediated phosphorylation.	SIGNOR-178494
Q96I25	P49759	0	phosphorylation	up-regulates activity	0.317	In this work, we show that Cdc2-like kinase 1 (Clk1) phosphorylates SPF45 on eight serine residues.	SIGNOR-262710
P31751	P15056	1	phosphorylation	down-regulates	0.272	We show that phosphorylation of b-raf by akt occurs at multiple residues within its amino terminal regulatory domain, at both the conserved and unique phosphorylation sites. Akt phosphorylated b-raf on s364 and s428 to inactivate its kinase activity b-raf contains three akt consensus sites, table i. One site, ser364 is conserved with c-raf;however, two sites, ser428 and thr439, are unique to b-raf	SIGNOR-78689
Q9NYA1	P27361	0	phosphorylation	up-regulates	0.601	Activation of sphingosine kinase 1 by erk1/2-mediated phosphorylation.	SIGNOR-118550
Q15375	P56915	0	transcriptional regulation	down-regulates quantity by repression	0.2	We demonstrate that Goosecoid can act as a repressor of its own promoter activity in transient co-transfection experiments in mouse P19 cells and in Xenopus embryos. Autorepression depends on the presence of the homeodomain and is mediated through the prd element more proximal to the transcriptional start site.	SIGNOR-261613
Q13887	Q05655	0	phosphorylation	up-regulates activity	0.335	Phosphorylation of Kruppel-like factor 5 (KLF5/IKLF) at the CBP interaction region enhances its transactivation function. \| Inhibition of protein kinase activity by H7 or calphostin C blocked both full-length and N-terminal fragment (amino acids 1-238) KLF5 activities. Mutation at a potential protein kinase C phosphorylation site within the CBP interaction domain of KLF5 reduces its transactivation function. Furthermore, using the GST pull-down approach, we showed that phosphorylation of KLF5 enhances its interaction with CBP. The results of the present study provide a mechanism for KLF5 transactivation function. \| We found that KLF5s activity was reduced to half when the serine in the potential PKC phosphorylation site was mutated to alanine (Fig. 6B, S153A) Nonetheless, the S153A mutant still retains significant transactivation activity.	SIGNOR-249206
Q00987	P04637	1	ubiquitination	down-regulates quantity by destabilization	0.968	The E3 ubiquitin ligase, MDM2, uses a dual-site mechanism to ubiquitinate and degrade the tumor suppressor protein p53, involving interactions with the N-terminal hydrophobic pocket and the acidic domain of MDM2.	SIGNOR-196116
P08754	Q9HC97	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-256860
Q86U44	Q13315	0	phosphorylation	up-regulates activity	0.2	Here, we report that, in response to DSBs, the RNA methyltransferase METTL3 is activated by ATM-mediated phosphorylation at S43.	SIGNOR-265969
P17612	O95644	1	phosphorylation	down-regulates	0.385	Here we show that overexpression of pka causes phosphorylation and cytoplasmic accumulation of nf-atc1 in direct opposition to calcineurin by phosphorylating ser-245, ser-269, and ser-294 in the conserved serine-proline repeat domainwe further show that a complete block of nf-atc1 nuclear localization by pka requires a second kinase activity that can be supplied by glycogen synthase kinase-3 (gsk-3)	SIGNOR-93531
P42771	P11802	2	binding	down-regulates	0.905	The first group, including p16ink4a, p15ink4b,p18ink4cand p19ink4d, is specific for the g1 cdks, cdk4 and cdk6, inhibiting the kinase activity of cyclin d/cdk4-cdk6 complexes on prb.	SIGNOR-44554
P17612	Q00059	1	phosphorylation	up-regulates	0.2	Here, we demonstrate that tfam is phosphorylated within its hmg box 1 (hmg1) by camp-dependent protein kinase in mitochondria. Hmg1 phosphorylation impairs the ability of tfam to bind dna and to activate transcription.	SIGNOR-199934
P10636	O96017	0	phosphorylation	down-regulates	0.2	Tau pseudophosphorylation at specific sites such as s262, s293, s324 and s356 was reported to induce tau conformational change and attenuate tau binding to microtubules (fischer et al., 2009). Then, newly soluble tau proteins are targeted by post-translational modifications that directly or indirectly alter tau conformation, promoting tau dimerization in an anti-parallel manner. Stable tau dimers form tau oligomers, which continue in the aggregation process	SIGNOR-171026
Q9Y463	P20823	1	phosphorylation	up-regulates	0.502	Mirk phosphorylates hnf1 at amino acid 249mkk3 enhanced mirk kinase activity and the transcriptional activation of hnf1alpha by mirk	SIGNOR-86728
Q8IYA7	P35711	1	transcriptional regulation	up-regulates quantity by expression	0.295	MKX is a meniscus-enriched transcription factor. In human meniscus cells, MKX regulates the expression of meniscus marker genes, OA-related genes, and other transcription factors, including Scleraxis (SCX), SRY Box 5 (SOX5), and Runt domain-related transcription factor 2 (RUNX2).	SIGNOR-267214

Q9NZS9

P55061

1

polyubiquitination

down-regulates quantity by destabilization

0.392

BAR overexpression promotes BI-1 ubiquitination and proteasomal degradation.We show here that bifunctional apoptosis regulator (BAR) functions as an ER-associated RING-type E3 ligase, interacts with BI-1, and promotes proteasomal degradation of BI-1.

SIGNOR-272778

K9N643

Q14164

2

binding

down-regulates activity

0.2

Previous studies have shown that MERS-CoV ORF4b antagonizes the early antiviral alpha/beta interferon (IFN-α/β) response, which may significantly contribute to MERS-CoV pathogenesis; however, the underlying mechanism is poorly understood. Here, we found that ORF4b in the cytoplasm could specifically bind to TANK binding kinase 1 (TBK1) and IκB kinase epsilon (IKKε), suppress the molecular interaction between mitochondrial antiviral signaling protein (MAVS) and IKKε, and inhibit IFN regulatory factor 3 (IRF3) phosphorylation and subsequent IFN-β production. these results indicate that MERS-CoV ORF4b inhibits the induction of type I IFN through a direct interaction with IKKε/TBK1 in the cytoplasm

SIGNOR-260592

P49757

P08151

2

binding

down-regulates

0.623

The consequent activation of_ itch, together with the recruitment of gli1 through direct binding with_ numb, allows gli1 to enter into the complex, resulting in gli1 ubiquitination and degradation.

SIGNOR-167841

Q53ET0

P35558

1

transcriptional regulation

up-regulates quantity

0.386

These results reveal that CRTC2 plays an essential role in the regulation of hepatic gluconeogenesis through coordinated regulation of the glucocorticoid/GR- and glucagon/CREB-signaling pathways on the key genes G6P and PEPCK.

SIGNOR-256106

P35221

P12830

2

binding

up-regulates

0.686

Additionally, the E-cadherin associated protein _-catenin regulates YAP directly by sequestering YAP/14-3-3 complexes in the cytoplasm.

SIGNOR-203468

P28482

P00533

1

phosphorylation

down-regulates activity

0.639

A growth factor-stimulated protein kinase activity that phosphorylates the epidermal growth factor (EGF) receptor at Thr669 has been described Anion-exchange chromatography demonstrated that this protein kinase activity was accounted for by two enzymes. The first peak of activity eluted from the column corresponded to the microtubule-associated protein 2 (MAP2) kinase

SIGNOR-20545

P17612

Q9NR82

1

phosphorylation

up-regulates activity

0.2

We conclude that phosphorylation of S53 on the amino terminus of Kv7.5 is essential for PKA-dependent enhancement of channel activity in response to βAR activation in vascular and airway smooth muscle cells.

SIGNOR-265980

P09017

O15550

0

transcriptional regulation

up-regulates quantity by expression

0.467

Evidence for direct involvement of UTX in regulation of HOX gene activity was demonstrated through UTX knockdown experiments in HEK293T cells in which loss of UTX induced transcriptional repression of HOXA and HOXC clusters.

SIGNOR-260030

O75581

P04628

2

binding

up-regulates activity

0.828

Ligands such as wnt1, wnt3a, and wnt8 couple the seventransmembrane domain receptor frizzled (fzd) and the single-membrane-spanning low-density receptor-related protein 5/6 (lrp5/6) to activate wnt?Beta-catenin signaling.

SIGNOR-169648

P35236

Q02156

0

phosphorylation

up-regulates activity

0.2

HePTP is phosphorylated by PKC isozymes at Ser-225 in vitro. While all isozymes phosphorylated Ser-225 predominantly and Ser-113 to a lesser extent (Fig. (Fig.5),5), they differed strikingly in how much 32P they incorporated into HePTP during the 30-min assay. PKC θ was the most efficient, while PKC ζ and PKC μ were clearly less potent; PKC δ, ɛ, and η were quite inefficient.

SIGNOR-276050

Q9NT99

P78352

2

binding

up-regulates activity

0.37

A possible function for the NGL–PSD-95 interaction is to couple trans-synaptic adhesion events to the recruitment of PSD-95 and other PSD-95-associated postsynaptic proteins. PSD-95 and liprin-α may be key synaptic scaffolding proteins that couple trans-synaptic adhesions to the assembly of synaptic proteins/vesicles

SIGNOR-264052

P23467

P06213

1

dephosphorylation

down-regulates

0.344

Identification of tyrosine phosphatases that dephosphorylate the insulin receptor.

SIGNOR-75997

P17676

P28845

1

transcriptional regulation

up-regulates quantity by expression

0.284

In conclusion, C/EBPalpha and C/EBPbeta control basal transcription, and TNF-alpha upregulates 11beta-HSD1, most likely by p38 MAPK-mediated increased binding of C/EBPbeta to the human HSD11B1 promoter.

SIGNOR-268972

O00451

P39905

2

binding

up-regulates

0.673

Gdnf mediates its actions through a multicomponent receptor system composed of a ligand-binding glycosyl-phosphatidylinositol (gpi)-linked protein (designated gdnfr-alpha).

SIGNOR-49184

Q8NEB9

P12931

0

phosphorylation

up-regulates activity

0.42

Given that VPS34 is activated by Src mediated tyrosine phosphorylation, we next determined if VPS34 was tyrosine phosphorylated following insulin treatment.|These data indicate that VPS34 is an effector of insulin-mediated signal transduction and that Src phosphorylation of VPS34 is required for this function.

SIGNOR-278456

Q13315

Q9Y297

1

phosphorylation

up-regulates quantity by stabilization

0.299

ATM phosphorylates and stabilizes β-TrCP1 upon DNA damage.

SIGNOR-277549

Q13541

P49841

0

phosphorylation

down-regulates activity

0.364

We found that gsk-3Beta phosphorylates and inactivates 4e-bp1, thereby increasing eif4e-dependent protein synthesis. upon stimulation, 4e-bp1 is phosphorylated on several threonine and serine residues, including thr-37/46 (36). This results in dissolution of the complex, freeing eif4e to bind with mrna cap to promote translation initiation.

SIGNOR-236026

P26927

P03952

0

cleavage

up-regulates activity

0.325

Proteolytic cleavage of pro-MSP at a single site yields active MSP, a disulfide-linked alphabeta-chain heterodimer. human kallikrein cleaved only at Arg483–Val484, the cleavage site for formation of a- and b-chains.

SIGNOR-256511

P46937

Q01538

0

transcriptional regulation

down-regulates quantity by repression

0.2

Myt1 and Myt1l transcription factors limit proliferation in GBM cells by repressing YAP1 expression. Examination of the gene expression changes in cells expressing Myt1 or Myt1l suggests that both repress expression of the YAP1 transcriptional coactivator, which functions primarily in the Hippo signaling pathway. Expression of YAP1 and its target genes is reduced in Myt-expressing cells, and there is an inverse correlation between YAP1 and MYT1/MYT1L expression in human brain cancer datasets. Together, our data suggest that Myt1 and Myt1l directly repress expression of YAP1, a protein which promotes proliferation and GBM growth.

SIGNOR-266777

O95352

P60520

2

binding

up-regulates activity

0.905

Three human atg8 (hatg8) homologs, lc3, gabarap, and gate-16, have been characterized as modifiers in reactions mediated by hatg7 (an e1-like enzyme) and hatg3 (an e2-like enzyme).

SIGNOR-142002

O15492

P00533

0

phosphorylation

up-regulates

0.415

Phosphorylation on tyr(168) was mediated by the epidermal growth factor receptor (egfr). We show here that endogenous rgs16 is phosphorylated after epidermal growth factor stimulation of mcf-7 cells.

SIGNOR-98267

P25098

P30411

1

phosphorylation

down-regulates activity

0.2

Ligand-induced phosphorylation is found at Ser339 and Ser346/Ser348 that could be executed by several G protein-coupled receptor kinases. 32P labeling of peptide 3 containing pS346/pS348 was enhanced 1.5–3-fold as compared with mock-transfected cells in the order GRK6 < GRK5 < GRK2 < GRK4α < GRK3. several endogenous GRKs may phosphorylate the B2R and that the various GRKs, even without apparent effect on total GPCR phosphorylation levels, may induce distinct phosphorylation patterns with possible functional consequences for receptor desensitization and sequestration.

SIGNOR-251445

O60260

P27695

1

ubiquitination

down-regulates quantity by destabilization

0.2

Based on these results, we conclude that Parkin directly ubiquitinates APE1.|These results indicated that degradation of APE1 by Parkin was limited compared to the transiently expressed APE1, suggesting that a large portion of APE1 is not in contact with the Parkin and PINK1 without induction of stresses such as oxidative stress.

SIGNOR-278531

Q9NRL3

Q9P2B4

2

binding

up-regulates activity

0.666

Although CTTNBP2 and CTTNBP2NL are different in terms of tissue and subcellular distribution, our data indicate that, similar to CTTNBP2NL, CTTNBP2 associates with members of the striatin family, namely striatin and zinedin. Moreover, CTTNBP2 is critical for the distribution of striatin and zinedin in dendritic spines. The role of CTTNBP2 in the regulation of the synaptic distribution of striatin and zinedin suggests that CTTNBP2 regulates synaptic signaling through PP2A.

SIGNOR-261701

Q96J92

P12931

0

phosphorylation

down-regulates activity

0.2

Using Western blot and mass spectrometry, we now identify three sites in WNK4 that are phosphorylated by c-Src: Tyr(1092), Tyr(1094), and Tyr(1143), and show that both c-Src and protein tyrosine phosphatase type 1D (PTP-1D) coimmunoprecipitate with WNK4.

SIGNOR-276897

Q15185

P68400

0

phosphorylation

up-regulates

0.354

Several lines of evidence suggest that a cpges-activating protein kinase is ck-ii (casein kinase ii). Recombinant cpges was phosphorylated directly by and associated with ck-ii in vitro, resulting in marked reduction of the k m for the substrate pgh2.

SIGNOR-123594

P63096

Q92633

2

binding

up-regulates activity

0.555

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-256696

P10909

O14920

2

binding

down-regulates quantity by destabilization

0.2

CLU-2 is a ubiquitin binding protein (UBP) that enhances proteasome activity. sCLU promotes degradation of COMMD1. sCLU interacts with the SCF-βTrCP E3 ligase complex, serving as a scaffolding chaperone to form a multimeric protein complex that facilitates COMMD1 and I-κB ubiquitination and proteasomal degradation.

SIGNOR-271433

P68431

Q92830

0

acetylation

down-regulates activity

0.2

The HAT module within the SAGA and ADA complexes acetylates histone H3, mainly on residues K9 and K14.

SIGNOR-269602

Q9BY84

Q9UQF2

2

binding

up-regulates

0.44

Here we report that jip-1 also binds the dual-specificity phosphatases mkp7 and m3/6 via a region independent of its jnk binding domain. when mkp7 is bound to jip-1 it reduces jnk activation leading to reduced phosphorylation of the jnk target c-jun

SIGNOR-97173

Q01484

Q9UJW0

1

relocalization

up-regulates quantity

0.625

We present evidence for an ankyrin-based mechanism for sarcolemmal localization of dystrophin and beta-DG. Ankyrin-B thus is an adaptor required for sarcolemmal localization of dystrophin, as well as dynactin-4.

SIGNOR-266713

P04150

P53041

0

dephosphorylation

down-regulates activity

0.541

Estrogen inhibits glucocorticoid action via protein phosphatase 5 (PP5)-mediated glucocorticoid receptor dephosphorylation.|Inhibition of GR phosphorylation at Ser-211 is associated with decreased nuclear retention of GR and decreased gene transcription.

SIGNOR-248538

P55212

P42574

0

cleavage

up-regulates

0.619

Caspase-3 is required for the activation of caspases 6

SIGNOR-64179

P78362

P48729

0

phosphorylation

up-regulates activity

0.25

Here, we demonstrate that mTORC1 promotes lipid biogenesis via SRPK2, a key regulator of RNA-binding SR proteins. mTORC1-activated S6K1 phosphorylates SRPK2 at Ser494, which primes Ser497 phosphorylation by CK1. These phosphorylation events promote SRPK2 nuclear translocation and phosphorylation of SR proteins.

SIGNOR-275460

P37173

P61812

2

binding

up-regulates

0.754

We show that tbetarii-b, an alternatively spliced variant of the tgf-beta type ii receptor, is a tgf-beta2 binding receptor, which mediates signalling via the smad pathway in the absence of any tgf-beta type iii receptor

SIGNOR-104795

O95999

O76064

0

ubiquitination

up-regulates quantity by stabilization

0.328

Phosphorylated and ubiquitinated BCL10 is stabilized on the damage sites through binding to and presenting UBC13 to RNF168.|We thus concluded that BCL10 is ubiquitinated mainly with K63-linked ubiquitination by RNF8.

SIGNOR-278778

P61587

Q13464

0

phosphorylation

up-regulates

0.707

We show that rock phosphorylates endogenous rhoe at serine 11 upon cell stimulation with platelet-derived growth factor. Phosphorylation has no effect on rhoe binding to rock i, but instead increases rhoe protein stability.

SIGNOR-134703

P10275

O15164

2

binding

up-regulates

0.396

We found that trim24/transcriptional intermediary factor 1alpha (tif1alpha), which is known as a ligand-dependent nuclear receptor co-regulator, interacts with ar and enhances transcriptional activity of ar

SIGNOR-189113

P24752

P11362

0

phosphorylation

up-regulates activity

0.2

Treatment with the FGFR1 inhibitor TKI258 in FGFR1-expressing H1299 cells led to decreased Y407 phosphorylation of ACAT1 in the mitochondrial fraction, where both ACAT1 and a fraction of FGFR1 were detected|Inhibition of tetrameric ACAT1 by abolishing Y407 phosphorylation or AH treatment results in decreased ACAT1 activity,

SIGNOR-264423

Q13557

Q9UQD0

1

phosphorylation

up-regulates activity

0.281

CaMKII enhances voltage-gated sodium channel Nav1.6 activity and neuronal excitability|mmobilized peptide arrays and nanoflow LC-electrospray ionization/MS of Nav1.6 reveal potential sites of CaMKII phosphorylation, specifically Ser-561 and Ser-641/Thr-642 within the first intracellular loop of the channel.

SIGNOR-275792

Q13635

Q99835

2

binding

down-regulates activity

0.786

We show that free Ptc (unbound by Hh) acts sub-stoichiometrically to suppress Smo activity and thus is critical in specifying the level of pathway activity.

SIGNOR-91709

O15169

P62140

0

dephosphorylation

down-regulates activity

0.2

The data suggest that PP1 controls Wnt signaling through interaction with, and regulated dephosphorylation of, axin| Axin phosphorylation markedly enhances the binding of glycogen synthase kinase 3, leading to a more active beta-catenin destruction complex. Wnt-regulated changes in axin phosphorylation, mediated by PP1, may therefore determine beta-catenin transcriptional activity| Four sites, S80, S82, S222, and S473, were identified to be PP1 regulated

SIGNOR-248567

P21728

O95837

2

binding

up-regulates activity

0.265

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-257391

P14618

P24666

0

dephosphorylation

up-regulates activity

0.279

Indeed, it is evident that LMW-PTP, hydrolyzing phosphotyrosine residues, contributes to maintain PKM2 in its active form.|We speculate that this effect is in large part due to LMW-PTP inhibition, which leads a fast PKM2 phosphorylation and inactivation.|we demonstrate that in melanoma cells the overexpression of LMW-PTP is functional to maintain PKM2 in its dephosphorylate status – the tetrameric, “full active” form - which is retained in the cytoplasm

SIGNOR-277134

Q92997

Q92945

2

binding

down-regulates

0.2

Ksrp was shown to interact with the c-terminus of dvl3. We show that ksrp negatively regulates wnt/beta-catenin signaling at the level of post-transcriptional ctnnb1 (beta-catenin) mrna stability.

SIGNOR-23800

P19174

Q07889

2

binding

up-regulates

0.647

We provide evidence that sos1, a p21ras-specific guanine nucleotide exchange factor, directly binds to the sh3 domain of plc-gamma1, and that the sh3 domain of plc-gamma1 is involved in sos1-mediated p21ras activation.

SIGNOR-80024

P15941

P00533

0

phosphorylation

up-regulates activity

0.577

We also show that the activated egf-r phosphorylates the muc1 cytoplasmic tail on tyrosine at a yekv motif that functions as a binding site for the c-src sh2 domain. The results demonstrate that egf-r-mediated phosphorylation of muc1 induces binding of muc1 to c-src in cells

SIGNOR-109538

Q13464

O14974

1

phosphorylation

down-regulates activity

0.774

Phosphorylation by Rho-kinase inhibited MP activity and this reflected a decrease in V(max). Activity of MP with different substrates also was inhibited by phosphorylation. Two major sites of phosphorylation on MYPT1 were Thr(695) and Thr(850).

SIGNOR-249034

P35348

P63092

2

binding

up-regulates activity

0.291

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 ‚â• -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 ‚â• -1.0 for defining true couplings. | The score associated to this interaction has a LogRAi ‚â• -1.0.

SIGNOR-256812

P01112

P20936

2

binding

down-regulates

0.848

The Ras protein sits at the center of a many-tiered cascade of molecular interactions. Most of the proteins along this cascade are activated by phosphorylation, but Ras uses a bound guanine nucleotide to toggle between its on and off states. Ras hydrolyzes GTP to GDP fairly quickly, turning itself off, and a collection of GTPase-activating proteins (GAPs) speed up the processthe complex between human h-ras bound to guanosine diphosphate and the guanosine triphosphatase (gtpase)-activating domain of the human gtpase-activating protein p120gap (gap-334) in the presence of aluminum fluoride was solved.

SIGNOR-68990

Q06609

P42229

0

transcriptional regulation

up-regulates quantity by expression

0.263

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-261552

Q9BW19

P06493

0

phosphorylation

up-regulates quantity by stabilization

0.458

We confirmed that CDK1 phosphorylates Ser6 (Supplementary Fig S5B) and demonstrated that KIFC1 displays CDK1-mediated resistance to ubiquitination by the APC/C (Fig S5C).

SIGNOR-277294

P15498

O15524

2

binding

down-regulates quantity by destabilization

0.598

SOCS1 stimulates the polyubiquitination of VAV proteins in vivo, which was stabilized by proteasomal inhibitors. These results suggest that SOCS1 programs VAV degradation by acting as a substrate-specific recognition component of a VCB-like ubiquitin ligase complex.

SIGNOR-272559

P22460

Q13131

0

phosphorylation

down-regulates activity

0.2

Thus, AMPK directly phosphorylates the  subunit of KV1.5 at Ser592 and, to a lesser extent, at Ser560

SIGNOR-277814

Q7RTT9

P19544

0

transcriptional regulation

up-regulates quantity by expression

0.274

ENT4 is transcriptionally activated by both isoforms of EWS/WT1 as evidenced by promoter-reporter and chromatin immunoprecipitation (ChIP) analyses.

SIGNOR-268985

P45983

Q9UPT6

2

phosphorylation

up-regulates

0.722

Phosphoamino acid analysis confirmed that jnk caused thr phosphorylation of jip3 (fig. _(fig.3c).3c). This phosphorylation on thr was markedly decreased when thr266, thr276, and thr287 were replaced with ala. These data indicate that jnk phosphorylated jip3 on thr266, thr276, and thr287 in vitro.

SIGNOR-134545

Q9HAU4

Q15797

1

polyubiquitination

down-regulates quantity by destabilization

0.725

Here, we report the identification of Smurf2, a new member of the Hect family of E3 ubiquitin ligases. Smurf2 selectively interacts with receptor-regulated Smads and preferentially targets Smad1 for ubiquitination and proteasome-mediated degradation. At higher expression levels, Smurf2 also decreases the protein levels of Smad2, but not Smad3.

SIGNOR-272936

O14867

P52789

1

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

P35626

P51681

1

phosphorylation

down-regulates activity

0.2

Serine residues at positions 336, 337, 342, and 349 represent GRK phosphorylation sites on CCR5. CCR5 phosphorylation and desensitization through a GRK-mediated mechanism

SIGNOR-251463

P51948

P03372

1

phosphorylation

up-regulates activity

0.397

Human Estrogen Receptor α Is Phosphorylated at Serine 118 In Vivo by Cdk7

SIGNOR-260837

Q9UKC9

Q96P20

2

binding

down-regulates quantity by destabilization

0.351

LPS exposure reduces the ubiquitin-mediated proteasomal processing of NALP3 by inducing levels of an E3 ligase component, FBXO3, which targets FBXL2. The latter is an endogenous mediator of NALP3 degradation. FBXL2 recognizes Trp-73 within NALP3 for interaction and targets Lys-689 within NALP3 for ubiquitin ligation and degradation.

SIGNOR-272432

O14976

P12931

0

phosphorylation

up-regulates activity

0.274

GAK is phosphorylated by c-Src and translocated from the centrosome to chromatin at the end of telophase. Cyclin G-associated kinase (GAK) harbors a consensus phosphorylation motif (Y412) for c-Src; however, its physiological significance remains elusive. Here, we show that GAK is phosphorylated by c-Src not only at Y412 but also at Y1149.

SIGNOR-263197

Q06124

P40763

1

dephosphorylation

down-regulates activity

0.77

In addition, SHP-2 dephosphorylates tyrosine-phosphorylated Stat1/3/5A (Ohtani et al., 2000; Wu et al., 2002; Chen et al., 2003), and downregulates Stat3-mediated biological actions (Ohtani et al., 2000).|Inhibition of collagen-induced Stat3 tyrosine-705 (Stat3-p-Tyr)

SIGNOR-272404

P68400

P55957

1

phosphorylation

up-regulates activity

0.286

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-250831

P10398

Q8IVT5

2

binding

up-regulates activity

0.567

In mammals, RAF family kinases include three catalytically competent enzymes (ARAF, BRAF and CRAF) and two pseudokinases (KSR1 and KSR2) that have been described as scaffolds owing to their apparent ability to bridge RAF isoforms and their substrate, mitogen-activated protein kinase kinase (MEK).Kinase suppressor of Ras (KSR) pseudokinases were also shown to dimerize with kinase-competent RAFs to stimulate catalysis allosterically.

SIGNOR-273876

O15393

P0DTC2

1

cleavage

up-regulates activity

0.2

Here, we demonstrate that SARS-CoV-2 uses the SARS-CoV receptor ACE2 for entry and the serine protease TMPRSS2 for S protein priming. The Cellular Serine Protease TMPRSS2 Primes SARS-2- S for Entry, and a Serine Protease Inhibitor Blocks SARS-CoV-2 Infection of Lung Cells

SIGNOR-260736

P0C1S8

P06493

1

phosphorylation

down-regulates activity

0.587

Recombinant Wee1B effectively phosphorylated cyclin B-associated Cdk1 on tyrosine-15, resulting in an inactivation of the kinase activity of Cdk1.

SIGNOR-279134

P45984

P15336

1

phosphorylation

up-regulates

0.698

Phosphorylation of thr-69 by mapk14 and mapk11, and at thr-71 by mapk1/erk2, mapk3/erk1, mapk11, mapk12 and mapk14 in response to external stimulus like insulin causes increased transcriptional activity.

SIGNOR-163266

Q9NS23

Q96GD4

0

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

Q13164

Q16828

0

dephosphorylation

down-regulates activity

0.646

However, whilst the interaction itself might be difficult to monitor, DUSP6 should still be able to promote the de-phosphorylation of ERK5 in cells if it is an ERK5 phosphatase.To test this HEK293 cells were transiently transfected with HA-ERK2 or HA-ERK5 together with EGFP-MEK1E (a constitutively active version of MEK1) or EGFP-MEK5D (a constitutively active version of MEK5).|Whilst one can envisage scenarios in which the interaction between DUSPs and their substrates might be transient, DUSP6 should still be able to promote the de-phosphorylation and inactivation of ERK5.

SIGNOR-277007

Q99683

P52564

1

phosphorylation

up-regulates activity

0.613

A MAP kinase kinase kinase (MAPKKK), termed ASK1, was identified that activated two different subgroups of MAP kinase kinases (MAPKK), SEK1 (or MKK4) and MKK3/MAPKK6 (or MKK6), which in turn activated stress-activated protein kinase (SAPK, also known as JNK; c-Jun amino-terminal kinase) and p38 subgroups of MAP kinases, respectively.

SIGNOR-45353

P54619

P54646

2

binding

up-regulates

0.897

Gamma non-catalytic subunit mediates binding to amp, adp and atp, leading to activate or inhibit ampk: amp-binding results in allosteric activation of alpha catalytic subunit (prkaa1 or prkaa2) both by inducing phosphorylation and preventing dephosphorylation of catalytic subunits.

SIGNOR-139173

P50148

P61586

2

binding

up-regulates

0.576

Recently, the dbl-family guanine nucleotide exchange factor (gef) p63rhogef/geft has been described as a novel mediator of galpha(q/11) signaling to rhoa based on its ability to synergize with galpha(q/11) resulting in enhanced rhoa signaling in cells.

SIGNOR-156534

P62805

O94874

0

ubiquitination

up-regulates activity

0.2

Here we report that UFM1 specific ligase 1 (UFL1), an ufmylation E3 ligase, is important for ATM activation.

SIGNOR-265072

Q5SGD2

O43318

1

dephosphorylation

down-regulates activity

0.585

Co-immunoprecipitation experiments indicated that PP2Cepsilon associates stably with TAK1 and attenuates the binding of TAK1 to MKK4 or MKK6.|PP2Cepsilon dephosphorylated TAK1 in vitro.

SIGNOR-277114

P43405

Q8IWV1

1

phosphorylation

up-regulates activity

0.378

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-273535

Q6P589

O43318

0

phosphorylation

down-regulates quantity by destabilization

0.2

TAK1 phosphorylated the Ser3 in the noncanonical degron motif of TIPE2 to trigger its interaction with β-TrCP for subsequent ubiquitination and degradation.

SIGNOR-273668

P05771

Q05639

1

phosphorylation

up-regulates activity

0.2

PKCβI phosphorylates eEF1A at Ser53.our proteomics exploration of cPKC signaling in the nuclei of C2C12 cells demonstrated that the up-regulation of eEF1A intranuclear content, evoked by insulin, is associated with an increase in the phosphorylation of the Ser53 residue of the protein.

SIGNOR-263166

P27361

P15056

1

phosphorylation

down-regulates

0.645

Erk-induced phosphorylation of b-raf on t753 promoted the disassembly of raf heterodimers, and the mutation of t753 prolonged growth factor-induced heterodimerization. The b-raf t753a mutant enhanced differentiation of pc12 cells, which was previously shown to be dependent on sustained erk signaling. Site is critical for v-src dependent modulation of slk kinase activity.

SIGNOR-144827

O43597

P12931

0

phosphorylation

up-regulates

0.565

Activation of signalling by fibroblast growth factor receptor leads to phosphorylation of the signalling attenuator human sprouty 2 (hspry2) on residue y55. we show that hspry2 is a direct substrate for src family kinases, including src itself.Phosphorylation of hspry2 is required for hspry2 to inhibit activation of the extracellular signal-regulated kinase pathway.

SIGNOR-131189

P06730

Q13490

0

ubiquitination

down-regulates quantity by destabilization

0.401

We found that endogenous eIF4E was ubiquitinated by cIAP1, and ubiquitinated eIF4E accumulated upon MG132 treatment.

SIGNOR-278741

Q92830

P11802

0

phosphorylation

up-regulates activity

0.36

Activated cyclin D1-Cdk4 kinase phosphorylates and activates GCN5|GCN5 T272A/S372A (AA) phosphorylation by cyclin D1-CDK4 kinase is diminished compared to GCN5 wild-type (WT)

SIGNOR-275494

P02452

P13497

0

cleavage

up-regulates activity

0.681

BMP-1myc Expressed in COS-7 Cells Exhibits Procollagen C-proteinase Activity. Bone morphogenetic protein (BMP)-1, which belongs to the tolloid subgroup of astacin-like zinc metalloproteinases, cleaves the C-propeptides of procollagen at the physiologic site and is, therefore, a procollagen C-proteinase (PCP). Cleavage occurs between a specific alanine or glycine residue (depending on the procollagen chain) and an invariant aspartic acid residue in each of the three chains of procollagen.

SIGNOR-256342

O14640

O60353

2

binding

up-regulates activity

0.678

When canonical wnts bind to their respective fzd receptors, heterotrimeric g-proteins and dsh get activated and lead to the recruitment of axin to the fzd co-receptor lrp.

SIGNOR-198828

P0C0L5

Q96PZ7

2

binding

down-regulates quantity

0.2

CUB and sushi multiple domains 1 (CSMD1) is a relatively poorly studied large transmembrane protein of 390 kDa composed of 14 N-terminal CUB domains interspersed with complement control protein (CCP) domains followed by 15 consecutive CCP domains. The active domains of CSMD1 were then identified in CCP17-21, which were shown to interact with C4b and C3b and present these complement proteins for degradation by factor

SIGNOR-265149

P23458

P16871

2

binding

up-regulates

0.638

For instance, jak1 is associated with the ? Subunits of ?c Cytokines such as il-7r? And IL-4R. jak3 is associated with the ?c20,21. Cytokine binding mediates the trans-phosphorylation of receptor associated jak kinases, which in turn phosphorylate tyrosine residues on the receptors themselves. The receptor phosphotyrosines serve as docking sites for sh2 domain proteins including the stat family of transcription factors which are activated by jak-mediated phosphorylation.

SIGNOR-178494

Q96I25

P49759

0

phosphorylation

up-regulates activity

0.317

In this work, we show that Cdc2-like kinase 1 (Clk1) phosphorylates SPF45 on eight serine residues.

SIGNOR-262710

P31751

P15056

1

phosphorylation

down-regulates

0.272

We show that phosphorylation of b-raf by akt occurs at multiple residues within its amino terminal regulatory domain, at both the conserved and unique phosphorylation sites. Akt phosphorylated b-raf on s364 and s428 to inactivate its kinase activity b-raf contains three akt consensus sites, table i. One site, ser364 is conserved with c-raf;however, two sites, ser428 and thr439, are unique to b-raf

SIGNOR-78689

Q9NYA1

P27361

0

phosphorylation

up-regulates

0.601

Activation of sphingosine kinase 1 by erk1/2-mediated phosphorylation.

SIGNOR-118550

Q15375

P56915

0

transcriptional regulation

down-regulates quantity by repression

0.2

We demonstrate that Goosecoid can act as a repressor of its own promoter activity in transient co-transfection experiments in mouse P19 cells and in Xenopus embryos. Autorepression depends on the presence of the homeodomain and is mediated through the prd element more proximal to the transcriptional start site.

SIGNOR-261613

Q13887

Q05655

0

phosphorylation

up-regulates activity

0.335

Phosphorylation of Kruppel-like factor 5 (KLF5/IKLF) at the CBP interaction region enhances its transactivation function. | Inhibition of protein kinase activity by H7 or calphostin C blocked both full-length and N-terminal fragment (amino acids 1-238) KLF5 activities. Mutation at a potential protein kinase C phosphorylation site within the CBP interaction domain of KLF5 reduces its transactivation function. Furthermore, using the GST pull-down approach, we showed that phosphorylation of KLF5 enhances its interaction with CBP. The results of the present study provide a mechanism for KLF5 transactivation function. | We found that KLF5s activity was reduced to half when the serine in the potential PKC phosphorylation site was mutated to alanine (Fig. 6B, S153A) Nonetheless, the S153A mutant still retains significant transactivation activity.

SIGNOR-249206

Q00987

P04637

1

ubiquitination

down-regulates quantity by destabilization

0.968

The E3 ubiquitin ligase, MDM2, uses a dual-site mechanism to ubiquitinate and degrade the tumor suppressor protein p53, involving interactions with the N-terminal hydrophobic pocket and the acidic domain of MDM2.

SIGNOR-196116

P08754

Q9HC97

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-256860

Q86U44

Q13315

0

phosphorylation

up-regulates activity

0.2

Here, we report that, in response to DSBs, the RNA methyltransferase METTL3 is activated by ATM-mediated phosphorylation at S43.

SIGNOR-265969

P17612

O95644

1

phosphorylation

down-regulates

0.385

Here we show that overexpression of pka causes phosphorylation and cytoplasmic accumulation of nf-atc1 in direct opposition to calcineurin by phosphorylating ser-245, ser-269, and ser-294 in the conserved serine-proline repeat domainwe further show that a complete block of nf-atc1 nuclear localization by pka requires a second kinase activity that can be supplied by glycogen synthase kinase-3 (gsk-3)

SIGNOR-93531

P42771

P11802

2

binding

down-regulates

0.905

The first group, including p16ink4a, p15ink4b,p18ink4cand p19ink4d, is specific for the g1 cdks, cdk4 and cdk6, inhibiting the kinase activity of cyclin d/cdk4-cdk6 complexes on prb.

SIGNOR-44554

P17612

Q00059

1

phosphorylation

up-regulates

0.2

Here, we demonstrate that tfam is phosphorylated within its hmg box 1 (hmg1) by camp-dependent protein kinase in mitochondria. Hmg1 phosphorylation impairs the ability of tfam to bind dna and to activate transcription.

SIGNOR-199934

P10636

O96017

0

phosphorylation

down-regulates

0.2

Tau pseudophosphorylation at specific sites such as s262, s293, s324 and s356 was reported to induce tau conformational change and attenuate tau binding to microtubules (fischer et al., 2009). Then, newly soluble tau proteins are targeted by post-translational modifications that directly or indirectly alter tau conformation, promoting tau dimerization in an anti-parallel manner. Stable tau dimers form tau oligomers, which continue in the aggregation process

SIGNOR-171026

Q9Y463

P20823

1

phosphorylation

up-regulates

0.502

Mirk phosphorylates hnf1 at amino acid 249mkk3 enhanced mirk kinase activity and the transcriptional activation of hnf1alpha by mirk

SIGNOR-86728

Q8IYA7

P35711

1

transcriptional regulation

up-regulates quantity by expression

0.295

MKX is a meniscus-enriched transcription factor. In human meniscus cells, MKX regulates the expression of meniscus marker genes, OA-related genes, and other transcription factors, including Scleraxis (SCX), SRY Box 5 (SOX5), and Runt domain-related transcription factor 2 (RUNX2).

SIGNOR-267214