GleghornLab/Signor_processed · Datasets at Hugging Face

IdA stringlengths 6 21	IdB stringlengths 6 21	mechanism stringclasses 40 values	effect stringclasses 10 values	score float64 0.1 0.99 ⌀	sentence stringlengths 10 1.63k ⌀	signor_id stringlengths 12 14
Q9ULW0	Q00535	phosphorylation	up-regulates quantity by stabilization	0.272	CDK5-mediated phosphorylation and stabilization of TPX2 promotes hepatocellular tumorigenesis	SIGNOR-265100
P04049	O60346	dephosphorylation	down-regulates activity	0.272	PHLPP1 and PHLPP2 dephosphorylate RAF1 to reduce its signaling, increase the invasive and migratory activities of CRC cells, and activate the epithelial-mesenchymal transition. In Apc(Min) mice, loss of PHLPP1 promotes tumor progression.	SIGNOR-237449
Q9Y4K3	P51812	phosphorylation	up-regulates activity	0.272	These results demonstrate that TRAF6 K63 ubiquitination might be regulated by an RSK2 mediated phosphorylation dependent mechanism and phosphorylation of TRAF6 at Ser46, 47 and 48 enhances its ubiquitin mediated inflammation signaling.	SIGNOR-278302
Q05397	Q9UQM7	phosphorylation	up-regulates	0.272	Furthermore, activated camkii directly phosphorylated the recombinant cooh-terminal region of fak at a residue equivalent to ser-843.	SIGNOR-135631
Q13526	P45983	phosphorylation	up-regulates quantity by stabilization	0.272	Mechanistically, the JNK kinases directly bind to and phosphorylate PIN1 at Ser115, and this phosphorylation prevents PIN1 mono-ubiquitination at Lys117 and its proteasomal degradation.	SIGNOR-277562
P09471	P25101	binding	up-regulates activity	0.272	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-257253
P26358	P49841	phosphorylation	down-regulates quantity	0.272	We determined that in a human lung cell line, glycogen synthase kinase 3beta (GSK3beta) phosphorylated DNMT1 to recruit beta-transducin repeat-containing protein (betaTrCP), resulting in DNMT1 degradation, and that NNK activated AKT, inhibiting GSK3beta function and thereby attenuating DNMT1 degradation.	SIGNOR-279181
P00519	Q04912	phosphorylation	up-regulates activity	0.272	This suggests that by interacting with Sdc4, either directly or indirectly, RON is activated via transphosphorylation when clustered, engages the ABL1 SH2 domain, and activates ABL1 by phosphorylation.	SIGNOR-272999
O43602	P49841	phosphorylation	up-regulates activity	0.271	Gsk3b phosphorylates dcx at the distinct site of ser327 and thereby contributes to dcx function in the restriction of axon branching. Together, our data define a jip3-regulated gsk3_/dcx signaling pathway that restricts axon branching in the mammalian brain.Gsk3_ induces the phosphorylation of dcx at ser327, which contributes to dcx function in the inhibition of axon branching and self-contact.	SIGNOR-170755
P22087	Q9NRC8	deacetylation	up-regulates activity	0.271	Here, we show that FBL is acetylated at several lysine residues by the acetyltransferase CBP and deacetylated by SIRT7.\|hyperacetylation impairs the interaction of FBL with histone H2A and chromatin, thereby compromising H2AQ104 methylation (H2AQ104me) and rDNA transcription. SIRT7-dependent deacetylation of FBL ensures H2AQ104me and high levels of rRNA synthesis during interphase. \|Global acetylome studies have shown that FBL is acetylated at four conserved lysine residues (K102, K121, K205, and K206)	SIGNOR-275894
P12235	Q06124	dephosphorylation	down-regulates activity	0.271	Specifically, SHP2-mediated dephosphorylation of ANT1 at Tyr 191 is essential for mitochondrial homeostasis and mitigation of NLRP3 inflammasome activation.\|The interaction between SHP2 and ANT1 (Fig.\u00a0 xref ), and the opposite effects of SHP2 and ANT1 shRNAs in the activation of NLRP3 inflammasome (Figs.\u00a0 xref and xref ) raised the possibility that the SHP2 may inhibit ANT1 to suppress NLRP3 inflammasome activation.\|To further determine which tyrosine phosphorylation site of ANT1 is dephosphorylated by SHP2, we created the dephosphorylated mutant of ANT1, in which tyrosine was replaced with phenylalanine (Y to F mutation).	SIGNOR-277124
Q969W9	P49910	transcriptional regulation	down-regulates quantity by repression	0.271	ZNF165 drives the unrestrained activation of transforming growth factor β (TGFβ) signalling by directly inactivating the expression of negative feedback pathway regulators, SMURF2, SMAD7 and PMEPA1.	SIGNOR-266094
Q96R06	P49841	phosphorylation	up-regulates	0.271	Astrin acts as a substrate for gsk3beta and is phosphorylated at thr-111, thr-937 ((s/t)p motif) and ser-974/thr-978 ((s/t)xxx(s/t)-p motif;p is a phosphorylatable residue). Inhibition of gsk3beta impairs spindle and kinetochore accumulation of astrin and spindle formation at mitosis, suggesting that astrin association with the spindle microtubule and kinetochore may be dependent on phosphorylation by gsk3beta	SIGNOR-159578
Q03014	Q01196	transcriptional regulation	up-regulates quantity	0.271	We identified Hhex as a direct target of RUNX1 and FLT3-ITD stimulation and confirmed high HHEX expression in FLT3-ITD AMLs. HHEX could replace RUNX1 in cooperating with FLT3-ITD to induce AML.	SIGNOR-256305
P0DP91	P00519	phosphorylation	up-regulates activity	0.271	These data raise the possibility that tyrosine phosphorylation of CSB by c-Abl promotes redistribution of CSB in the nucleus and enrichment of CSB in the nucleolus in response to oxidative stress	SIGNOR-279317
P61006	Q9BXM7	phosphorylation	down-regulates activity	0.271	For Rab8a, it was shown that serine 111 phosphorylation (pS111) is dependent on the protein kinase PINK1 and that mimicking the phosphorylation at S111 by a serine/glutamate substitution (S111E) impaired Rab8a activation by its cognate nucleotide exchange factor (GEF) Rabin8.	SIGNOR-260268
Q9UQD0	Q13555	phosphorylation	up-regulates activity	0.271	CaMKII enhances voltage-gated sodium channel Nav1.6 activity and neuronal excitability\|mmobilized peptide arrays and nanoflow LC-electrospray ionization/MS of Nav1.6 reveal potential sites of CaMKII phosphorylation, specifically Ser-561 and Ser-641/Thr-642 within the first intracellular loop of the channel.	SIGNOR-275794
P51114	Q13153	phosphorylation	up-regulates activity	0.271	Identification of Ser420 in FXR1 as a PAK1 Kinase Target. During zebrafish muscle development, FXR1 Ser420 phosphorylation is needed for protein function.	SIGNOR-273713
Q86U44	P27361	phosphorylation	up-regulates quantity by stabilization	0.271	Mass spectrometry analysis showed that ERK phosphorylates METTL3 at three highly conserved residues: S43, S50, and S525 (Figures 2D and 2E). Mutational analysis further confirmed these three sites as main ERK phosphorylation sites (Figure 2F). Phosphorylation of METTL3 increases interaction with USP5, decreasing ubiquitination to stabilize the m6 A methyltransferase complex.	SIGNOR-265949
Q8TCJ0	Q05655	phosphorylation	up-regulates activity	0.271	FBXO25 encodes an orphan F-box protein that determines the substrate specificity of the SCF (SKP1-CUL1-F-box)(FBXO25) ubiquitin ligase complex. An unbiased screen uncovered the prosurvival protein HCLS1-associated protein X-1 (HAX-1) as the bona fide substrate of FBXO25 that is targeted after apoptotic stresses. Protein kinase Cdelta (PRKCD) initiates this process by phosphorylating FBXO25 and HAX-1, thereby spatially directing nuclear FBXO25 to mitochondrial HAX-1.\|Accordingly, PRKCD-induced phosphorylation of Hax-1 at Ser210 and Fbxo25 at Ser178 was associated with decreased expression of Hax-1 in control cells,	SIGNOR-275561
Q14258	P12931	phosphorylation	up-regulates activity	0.271	Here, we demonstrated that TRIM25 interacted with c-Src and underwent tyrosine phosphorylation by c-Src kinase upon viral infection and the phosphorylation is required for the complete activation of RIG-I signaling. Analysis using a c-Src inhibitor and TRIM25 mutant, in which tyrosine 278 is substituted by phenylalanine (Y278F), suggested that the phosphorylation positively regulates K63-linked polyubiquitination of RIG-I and subsequent antiviral signaling.	SIGNOR-277405
Q00653	P49841	phosphorylation	down-regulates activity	0.271	More recently, phosphorylation of S707 and S711 by GSK3beta has been shown to promote complete proteasomal degradation of p100 involving the E3 ligase Fbw7 .\|These studies suggest that a pool of p100 is constitutively phosphorylated by GSK3beta at S707 and S711, triggering the Fbw7 mediated ubiquitination and proteasomal degradation of p100 which controls the levels of p100 available for the non canonical pathway.	SIGNOR-279186
P43405	Q13177	phosphorylation	up-regulates activity	0.271	This is supported by in vitro studies showing that Pak2 phosphorylates and activates Syk.	SIGNOR-279083
O94916	Q13315	phosphorylation	up-regulates	0.271	Tonebp/orebp contains atm consensus phosphorylation sites at ser-1197, ser-1247, and ser-1367. In conclusion, signaling via atm is necessary for full activation of tonebp/orebp	SIGNOR-125077
P55075	P40424	transcriptional regulation	down-regulates quantity by repression	0.271	Our results in ES cells suggest that Engrailed inhibits Fgf8 expression in the absence of Pbx1. We identified single Engrailed- and Pbx-binding sites in the Fgf8 intron that inhibit expression of Fgf8 in mouse ES cells, but that together can allow full Fgf8 expression. Our data support the model that Engrailed heterodimerized with Pbx might activate transcription, while Engrailed or Pbx proteins alone might repress transcription	SIGNOR-265803
P38405	P37288	binding	up-regulates activity	0.271	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-256948
P20138	P06239	phosphorylation	up-regulates	0.271	Human cd33 has two tyrosine residues in its cytoplasmic domain (y340 and y358). When phosphorylated, these tyrosines could function as docking sites for the phosphatases, shp-1 and/or shp-2, enabling cd33 to function as an inhibitory receptor. Lck is effective at phosphorylating y340	SIGNOR-78960
Q07866	P28482	phosphorylation	down-regulates	0.271	Phosphorylation of kinesin light chain 1 at serine 460 modulates binding and trafficking of calsyntenin-1mutation of klc1ser460 to an alanine residue, to preclude phosphorylation, increased the binding of calsyntenin-1, whereas mutation to an aspartate residueklc1ser460 is a predicted mitogen-activated protein kinase (mapk) target site, and we show that extracellular-signal-regulated kinase (erk) phosphorylates this residue in vitro.	SIGNOR-172638
Q14004	P22674	binding	up-regulates activity	0.271	Cyclin O promotes lung cancer progression and cetuximab resistance via cell cycle regulation and CDK13 interaction\|CCNO promoted tumor cell proliferation and survival in vivo via CDK13\|	SIGNOR-275618
Q99683	Q14680	phosphorylation	up-regulates activity	0.271	MELK, as an upstream kinase of ASK1, phosphorylates threonine 838 in an activation loop of human ASK1, thereby stimulating ASK1 kinase activity.	SIGNOR-280039
Q03468	P00519	phosphorylation	up-regulates activity	0.271	N-terminal region of CSB interacts with the SH3 domain of c-Abl in vitro and in vivo. In addition, c-Abl kinase phosphorylates CSB at Tyr932. our results suggest that c-Abl interacts with and tyrosine phosphorylates CSB. This interaction may play an important role in the response to oxidative stress, resulting in activation of c-Abl, tyrosine phosphorylation of CSB and more efficient BER of oxidative DNA damage. Tyrosine-phosphorylated CSB may serve as a signal for repair proteins to localize to DNA damage and may help maintain active transcription in the nucleolus.	SIGNOR-251933
P04049	P62136	dephosphorylation	up-regulates activity	0.271	We have identified a complex comprised of Shoc2/Sur-8 and the catalytic subunit of protein phosphatase 1 (PP1c) as a highly specific M-Ras effector. M-Ras targets Shoc2-PP1c to stimulate Raf activity by dephosphorylating the S259 inhibitory site of Raf proteins	SIGNOR-251649
Q09472	Q9UPU5	deubiquitination	up-regulates quantity by stabilization	0.271	In this study, several cancer-related proteins (Bax, p300, E2F4 and securin) have been proven to be substrates of ubiquitin-specific peptidase 24 (USP24), and relevance has been shown between USP24 and its substrates in samples from clinical lung cancer patients. \|Knockdown of USP24 decreases Bax and p300 levels	SIGNOR-275607
P12931	Q92945	post transcriptional regulation	up-regulates quantity by expression	0.271	We show here that this component of the DCS complex is hnRNP H and that, like hnRNP F and KSRP, hnRNP H is needed for src N1 splicing in vitro.	SIGNOR-261274
P31749	P31152	phosphorylation	up-regulates activity	0.271	Mechanistically, MAPK4 directly bound and activated AKT by phosphorylation of the activation loop at threonine 308.	SIGNOR-275450
Q8WZ42	P17252	phosphorylation	up-regulates activity	0.271	In summary, titin is a PKC substrate with PKCalpha phosphorylating predominately the full-length titin molecule.\|Mechanical experiments with skinned LV myocardium revealed that PKCalpha significantly increases titin based passive tension, an effect that is reversed by PP1.	SIGNOR-278382
Q9UI12	Q92544	binding	up-regulates activity	0.271	Here, we demonstrate that TM9SF4 represents a novel V-ATPase-associated protein involved in V-ATPase activation. We have observed in HCT116 and SW480 colon cancer cell lines that TM9SF4 interacts with the ATP6V1H subunit of the V-ATPase V1 sector. Suppression of TM9SF4 with small interfering RNAs strongly reduces assembly of V-ATPase V0/V1 sectors, thus reversing tumor pH gradient with a decrease of cytosolic pH, alkalization of intracellular vesicles and a reduction of extracellular acidity.	SIGNOR-266885
Q9BRS8	P08670	binding	up-regulates activity	0.271	Interaction of LARP6 with vimentin.Here, we report that vimentin filaments associate with collagen mRNAs in a 5'SL- and LARP6-dependent manner and stabilize collagen mRNAs. LARP6 interacts with vimentin filaments through its La domain and colocalizes with the filaments in vivo.	SIGNOR-277624
P51665	Q05086	ubiquitination	down-regulates quantity by destabilization	0.271	Our experiments collectively suggest that UBE3A stimulates Wnt pathway activation by interacting with, ubiquitinating, and reducing the levels of multiple (PSMB1, PSMC2, PSMD2, and PSMD7) proteasome subunits.	SIGNOR-265134
P42566	Q93008	deubiquitination	down-regulates activity	0.271	We identify the endocytic protein Eps15 as one of the critical substrates of USP9X	SIGNOR-245052
P40763	Q15678	dephosphorylation	down-regulates activity	0.271	Moreover, dephosphorylation of STAT3 by PTPN14 might occur in the cytoplasm but not in nucleus.\|The tyrosine phosphatase PTPN14 inhibits the activation of STAT3 in PEDV infected Vero cells.	SIGNOR-277088
Q9NPH5	P06241	phosphorylation	down-regulates activity	0.271	We found that direct phosphorylation of tyrosine 566 on NOX4 was critical for this FYN-mediated negative regulation.	SIGNOR-277273
Q9UGL1	Q16665	transcriptional regulation	up-regulates quantity by expression	0.271	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-271563
Q9Y4P8	Q8TEV9	transcriptional regulation	up-regulates quantity	0.271	Global mRNA expression analysis revealed that SMCR8 regulates transcription of several other autophagy genes including WIPI2	SIGNOR-252028
P10636-2	Q02156	phosphorylation	down-regulates activity	0.271	We have studied the relationship between the phosphorylation oftau by several kinases (MARK, PKA, MAPK, GSK3) and its assembly into PHFs. By contrast, MARK and PKA phosphorylate several sites within the repeats (notably theKXGS motifs including Ser262, Ser324, and Ser356, plus Ser320); in addition PKA phosphorylates somesites in the flanking domains, notably Ser214. This type of phosphorylation strongly reduces tau’s affinityfor microtubules, and at the same time inhibits tau’s assembly into PHFs.	SIGNOR-275444
P49841	Q05655	phosphorylation	down-regulates activity	0.271	In the TFEB activation pathway, activated PKC\u03b4 phosphorylates and inactivates GSK3\u03b2, leading to the reduced phosphorylation of TFEB at Ser134 and Ser138 residues; this reduced phosphorylation is critical for the cytoplasmic sequestration of TFEB.\|In the TFEB activation pathway, activated PKCdelta phosphorylates and inactivates GSK3beta, leading to the reduced phosphorylation of TFEB at Ser134 and Ser138 residues; this reduced phosphorylation is critical for the cytoplasmic sequestration of TFEB.	SIGNOR-280084
P63096	Q8IYL9	binding	up-regulates activity	0.271	GPR65 is playing a critical role in phagocytic cells that require high levels of V-ATPase activity to maintain phagosomal and lysosomal pH, and this activity aids in the direct clearance of enteric pathogens.	SIGNOR-272502
Q13188	Q9Y243	phosphorylation	down-regulates	0.271	Akt phosphorylates mst2 at thr117 in vitro and in vivo, which leads to mst2 cleavage and kinase activity as well as nuclear translocation.	SIGNOR-164306
P78527	P07949	phosphorylation	up-regulates activity	0.27	Phosphorylation of DNA-PKcs at s2056 is elevated in RET expressing cells and can be reduced by RET inhibition.	SIGNOR-279275
P12830	P48730	phosphorylation	down-regulates activity	0.27	Casein kinase 1 is a novel negative regulator of E-cadherin-based cell-cell contacts\|CK1 colocalizes with E-cadherin and phosphorylates the cytoplasmic domain of E-cadherin in vitro and in a cell culture system. We show that the major CK1 phosphorylation site of E-cadherin is serine 846	SIGNOR-274046
Q92915	P67870	phosphorylation	up-regulates activity	0.27	Bioluminescence-based screening of small molecule modulators of the FGF14:Nav1.6 complex identified 4,5,6,7 -: tetrabromobenzotriazole (TBB), a potent casein kinase 2 (CK2) inhibitor, as a strong suppressor of FGF14:Nav1.6 interaction. Inhibition of CK2 through TBB reduces the interaction of FGF14 with Nav1.6 and Nav1.2 channels. Mass spectrometry confirmed direct phosphorylation of FGF14 by CK2 at S228 and S230, and mutation to alanine at these sites modified FGF14 modulation of Nav1.6-mediated currents.	SIGNOR-275745
P22087	Q92793	acetylation	down-regulates activity	0.27	Here, we show that FBL is acetylated at several lysine residues by the acetyltransferase CBP and deacetylated by SIRT7.\|hyperacetylation impairs the interaction of FBL with histone H2A and chromatin, thereby compromising H2AQ104 methylation (H2AQ104me) and rDNA transcription. SIRT7-dependent deacetylation of FBL ensures H2AQ104me and high levels of rRNA synthesis during interphase. \|Global acetylome studies have shown that FBL is acetylated at four conserved lysine residues (K102, K121, K205, and K206)	SIGNOR-275897
Q8WYQ5	Q13315	phosphorylation	up-regulates quantity by stabilization	0.27	Specifically, radiation-induced ATM-dependent phosphorylation of DGCR8 at serine 677 facilitates USP51 to bind, deubiquitinate, and stabilize DGCR8, which leads to the recruitment of DGCR8 and DGCR8's binding partner RNF168 to MDC1 and RNF8 at DSBs.	SIGNOR-277307
Q9BQQ3	P28482	phosphorylation	down-regulates activity	0.27	Here we show that GRASP65 is phosphorylated on serine 277 in interphase cells, and this is strongly enhanced in response to the addition of serum or epidermal growth factor. This is directly mediated by ERK suggesting that GRASP65 has some role in growth factor signal transduction. These results argue against Ser-277 phosphorylation alone causing the dissolution of GRASP65 oligomers and cisternal unstacking, although it may make a significant contribution to these events.	SIGNOR-262841
P81274	Q96KB5	phosphorylation	up-regulates	0.27	We found that the 450th threonine (thr450) of lgn/gpsm2 was phosphorylated by the serine/threonine kinase pbk/topk during mitosis. Western blot analysis indicated the highest expression and the phosphorylated form of lgn/gpsm2 protein in g2/m phase.	SIGNOR-166461
P06213	Q9HD43	dephosphorylation	down-regulates	0.27	These results, combined with secondary dephosphorylation tests, confirm and extend earlier findings that ptp-1b and t-cell ptp are physiological enzymes for the insulin receptor kinase	SIGNOR-76072
O14672	P22415	transcriptional regulation	up-regulates quantity by expression	0.27	The promoter region of ADAM10 contains several transcription factor binding sites that can stimulate its transcription. These include binding sites for transcription factors SP1 and USF, and the spliced form of the X-box binding protein (XBP)-1 as well as a retinoic acid-responsive element	SIGNOR-259837
P08670	Q00535	phosphorylation	up-regulates activity	0.27	Cdk5 mediates vimentin Ser56 phosphorylation during GTP-induced secretion by neutrophils.	SIGNOR-278922
P08908	Q00535	phosphorylation	down-regulates quantity by destabilization	0.27	Cyclin-dependent kinase 5 promotes proteasomal degradation of the 5-HT 1A receptor via phosphorylation\|5-HT1AR was phosphorylated by the Cdk5-p35 complex at Thr314 in the third cytoplasmic loop.	SIGNOR-264406
Q8ND25	P00533	phosphorylation	up-regulates activity	0.27	Together, these results demonstrate that EGFR-dependent phosphorylation of ZNRF1 at Y103 promotes degradation of AKT and resultant activation of GSK3\u03b2, which mediates oxidative stress\u2013induced neuronal apoptosis ( xref ).	SIGNOR-279522
P19086	P43115	binding	up-regulates activity	0.27	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-257111
P08151	Q16539	phosphorylation	down-regulates quantity by destabilization	0.27	Here, we show that SHH inactivates p38α (MAPK14) in a smoothened-dependent manner, conversely, p38α directly phosphorylates GLI1 on Ser937/Ser941 (human/mouse) to induce GLI1's proteasomal degradation and negates the transcription of SHH signaling.	SIGNOR-277916
P53805	P28482	phosphorylation	up-regulates activity	0.27	Consensus phosphorylation sites for p42/44 MAPK and GSK-3 are present in the SP repeat of MCIP1 at serine 112 and serine 108, respectively \|Several endogenous proteins are capable of inhibiting the catalytic activity of calcineurin. Modulatory calcineurin interacting protein 1 (MCIP1) is unique among these proteins on the basis of its pattern of expression and its function in a negative feedback loop to regulate calcineurin activity. Here we show that MCIP1 can be phosphorylated by MAPK and glycogen synthase kinase-3 and that phosphorylated MCIP1 is a substrate for calcineurin.	SIGNOR-249198
P38405	P32245	binding	up-regulates activity	0.27	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-256940
P20719	O15550	transcriptional regulation	up-regulates quantity by expression	0.27	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-260023
P37840	P53355	phosphorylation	up-regulates quantity	0.27	We demonstrated that DAPK1 directly phosphorylates \u03b1-synuclein at Ser129, and induces the formation of insoluble \u03b1-synuclein aggregates.	SIGNOR-278440
P49662	Q63HK5	transcriptional regulation	down-regulates quantity by repression	0.27	Chromatin immunoprecipitation showed a direct interaction of FE65 and Teashirt3 with the promoter region of CASP4. The results were consistent with a model in which reduced expression of Teashirt3, mediated by genetic or other causes, increases caspase-4 expression, leading to progression of AD.	SIGNOR-264815
P10636-2	P05129	phosphorylation	down-regulates activity	0.27	We have studied the relationship between the phosphorylation oftau by several kinases (MARK, PKA, MAPK, GSK3) and its assembly into PHFs. By contrast, MARK and PKA phosphorylate several sites within the repeats (notably theKXGS motifs including Ser262, Ser324, and Ser356, plus Ser320); in addition PKA phosphorylates somesites in the flanking domains, notably Ser214. This type of phosphorylation strongly reduces tau’s affinityfor microtubules, and at the same time inhibits tau’s assembly into PHFs.	SIGNOR-275445
O60716	P28482	phosphorylation	down-regulates activity	0.27	Upon TGFβ treatment, activated extracellular signal-regulated kinase 1/2 (ERK1/2) phosphorylates T900 of p120-catenin to promote its interaction with Smurf1 and subsequent monoubiquitination. TGFβ promotes monoubiquitination of p120-catenin through Smurf1 to induce junction dissociation.	SIGNOR-277505
P48167	P12931	phosphorylation	up-regulates	0.27	These findings indicate that glyr function is upregulated by ptks and this modulation is dependent on the tyrosine-413 residue of the beta subunit.	SIGNOR-115705
P19338	P60484	dephosphorylation	up-regulates activity	0.27	The fact that PTEN\u03b2 interacts with nucleolin and dephosphorylates nucleolin at Thr84 raised a question as to whether nucleolin mediates PTEN\u03b2 regulation of rDNA transcription, and thus represents a direct mechanism by which PTEN\u03b2 controls ribosomal biogenesis.	SIGNOR-277166
Q13114	Q96PU5	ubiquitination	up-regulates activity	0.27	Nedd4l promotes TRAF3 to interact with cIAP1/2 and HECTD3.\|Ubiquitination of TRAF3 by Nedd4l promotes interaction of TRAF3 with proteins such as cIAP1/2, HECTD3, and TBK1.	SIGNOR-278587
Q12756	P0DP25	binding	up-regulates activity	0.27	To better understand how KIF1A-driven dense core vesicle (DCV) transport is regulated, we identified the KIF1A interactome and focused on three binding partners, the calcium binding protein calmodulin (CaM) and two synaptic scaffolding proteins: liprin-α and TANC2. We showed that calcium, acting via CaM, enhances KIF1A binding to DCVs and increases vesicle motility. In contrast, liprin-α and TANC2 are not part of the KIF1A-cargo complex but capture DCVs at dendritic spines. we can conclude that TANC2 and liprin-α are enriched in dendritic spines and interact with various synaptic proteins. TANC2 and Liprin-α2 Act as Immobile Postsynaptic Posts Able to Recruit KIF1A in a Subset of Dendritic Spines	SIGNOR-266890
Q2M2I8	Q15208	phosphorylation	up-regulates activity	0.27	We identified 5 potential NDR1 substrates in the mouse brain and chose two for functional validation. We show that one NDR1 substrate is another kinase, AP-2 associated kinase-1 (AAK1) which regulates dendritic branching as a result of NDR1 phosphorylation. Another substrate is the Rab8 guanine nucleotide exchange factor (GEF) Rabin8 (a Sec2p homolog) which we find is involved in spine synapse formation. AAK1 phosphorylation regulates dendrite branching and length	SIGNOR-263034
P46531	P11309	phosphorylation	up-regulates activity	0.27	Interestingly, Pim1 phosphorylated Notch1 and Notch3, but not Notch2 ICD (Figure xref ), which was in line with the observed Pearson correlations ( xref ).\|Our data indicate that endogenous Pim1 and Notch1 interact already in the cytoplasm, which supports the notion that Pim1 enhances nuclear localization and activity of Notch1.	SIGNOR-279643
P78352	P35637	post transcriptional regulation	up-regulates quantity	0.27	These results point toward a novel mechanism by which FUS targets neuronal mRNA and given that these PSD-95 and Shank1 3'-UTR G quadruplex structures are also targeted by the fragile X mental retardation protein (FMRP), they raise the possibility that FUS and FMRP might work together to regulate the translation of these neuronal mRNA targets.\|As seen in Figure 7 (top panel), both PSD-95 Q1-Q2 and Shank1a GQ probes pulled down endogenous FUS, whereas their M2 mutants did not, indicating that the GQ structure is sufficient for recognition.	SIGNOR-262103
Q02750	O15530	phosphorylation	up-regulates activity	0.27	In vitro kinase assay revealed that the direct targets of pdk1 in the mapk pathway were the upstream mapk kinases mek1 and mek2. The identified pdk1 phosphorylation sites in mek1 and mek2 are ser222 and ser226, respectively, and are known to be essential for full activation	SIGNOR-236633
P32754	A6NLP5	binding	up-regulates quantity by stabilization	0.27	Decreased expression of 4-hydroxyphenylpyruvic acid dioxygenase (HPD), a key enzyme for tyrosine metabolism, is a cause of human tyrosinemia. However, the regulation of HPD expression remains largely unknown. Here, we demonstrate that molecular chaperone TTC36, which is highly expressed in liver, is associated with HPD and reduces the binding of protein kinase STK33 to HPD, thereby inhibiting STK33-mediated HPD T382 phosphorylation. The reduction of HPD T382 phosphorylation results in impaired recruitment of FHA domain-containing PELI1 and PELI1-mediated HPD polyubiquitylation and degradation.	SIGNOR-272960
O60716	P07333	phosphorylation	up-regulates quantity by stabilization	0.27	In our study, CSF-1R induced the tyrosine phosphorylation of p120 Y904 and Y228 in a SRC-dependent manner ( xref ).	SIGNOR-278929
O95466	Q05655	phosphorylation	up-regulates activity	0.27	PKC\u03b4 induces FMNL1 phosphorylation.	SIGNOR-279261
O60566	Q96SN8	transcriptional regulation	up-regulates quantity by expression	0.27	These data indicate that CDK5RAP2 is a positive regulator of both the BUBR1 promoter and the MAD2 promoter	SIGNOR-260312
P08581	P51608	post transcriptional regulation	down-regulates quantity by repression	0.27	MeCP2 binding enhances MET expression in the presence of the rs1858830 C allele, but MET transcription is attenuated by RTT-specific mutations in MeCP2	SIGNOR-264683
P20749	P31751	phosphorylation	up-regulates quantity by stabilization	0.27	Here we show that Akt, Erk2, and IKK1/2 phosphorylate Bcl3. Phosphorylation of Ser33 by Akt induces switching of K48 ubiquitination to K63 ubiquitination and thus promotes nuclear localization and stabilization of Bcl3. Phosphorylation by Erk2 and IKK1/2 of Ser114 and Ser446 converts Bcl3 into a transcriptional coregulator by facilitating its recruitment to DNA.	SIGNOR-277359
Q15021	P51955	phosphorylation	down-regulates activity	0.269	Nek2 phosphorylates C-Nap1, rootletin and beta-catenin to regulate centrosome separation.	SIGNOR-279234
Q15139	Q05655	phosphorylation	up-regulates	0.269	Here we show that activation of pkd in response to oxidative stress requires two sequential signaling events, i.e., phosphorylation of tyr463 by abl, which in turn promotes a second step, phosphorylation of the pkd activation loop (ser738/ser742). We show that this is mediated by pkcdelta (protein kinase cdelta)	SIGNOR-123453
Q06413	Q32MK0	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
Q13315	P62714	dephosphorylation	down-regulates activity	0.269	Ionizing radiation induces autophosphorylation of the ataxia-telangiectasia mutated (ATM) protein kinase on serine 1981; however, the precise mechanisms that regulate ATM activation are not fully understood. Here, we show that the protein phosphatase inhibitor okadaic acid (OA) induces autophosphorylation of ATM on serine 1981 in unirradiated cells at concentrations that inhibit protein phosphatase 2A-like activity in vitro.	SIGNOR-248601
P19086	P21728	binding	up-regulates activity	0.269	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-257269
P37802	P28482	phosphorylation	up-regulates quantity by stabilization	0.269	ERK2 interacted with 29-31 amino acids of transgelin-2 and subsequently phosphorylated the S145 residue of transgelin-2. S145 phosphorylation of transgelin-2 played important roles in cell proliferation and tumorigenesis of PDAC.\| We found that the protein stability of transgelin-2 was regulated by KRAS. ERK-mediated phosphorylation resulted in accumulation of transgelin-2 protein.	SIGNOR-265221
Q92915	P68400	phosphorylation	up-regulates activity	0.269	Bioluminescence-based screening of small molecule modulators of the FGF14:Nav1.6 complex identified 4,5,6,7 -: tetrabromobenzotriazole (TBB), a potent casein kinase 2 (CK2) inhibitor, as a strong suppressor of FGF14:Nav1.6 interaction. Inhibition of CK2 through TBB reduces the interaction of FGF14 with Nav1.6 and Nav1.2 channels. Mass spectrometry confirmed direct phosphorylation of FGF14 by CK2 at S228 and S230, and mutation to alanine at these sites modified FGF14 modulation of Nav1.6-mediated currents.	SIGNOR-275738
Q01196	P11309	phosphorylation	up-regulates activity	0.269	Furthermore, catalytically active Pim-1 kinase was able to phosphorylate Runx1 and Runx3 proteins and enhance the transactivation activity of Runx1 in a dose-dependent fashion.\|Pim-1 potentiates transcriptional activity of the RUNX1 transcription factor.	SIGNOR-278976
P49715	Q15466	binding	down-regulates activity	0.269	SHP repressed C/EBPalpha (CCAAT/enhancer-binding protein alpha)-driven transcription of PEPCK through direct interaction with C/EBPalpha protein both in vitro and in vivo. The formation of an active transcriptional complex of C/EBPalpha and its binding to DNA was inhibited by SHP, resulting in the inhibition of PEPCK gene transcription.	SIGNOR-254831
P35580	Q05513	phosphorylation	down-regulates	0.269	After egf stimulation, apkc_ translocates from the nucleus to the cytoplasm (figure 3) and is therefore able to interact with myosin ii-b. apkc_ phosphorylates nmhc ii-b on ser1937, which is located on the nonhelical tailpiece, leading to filament disassembly at certain sites of the cell	SIGNOR-146100
P61586	Q9H3F6	binding	down-regulates quantity	0.269	BACURDs form ubiquitin ligase complexes, which selectively ubiquitinate RhoA, with Cul3. Our studies reveal a previously unknown mechanism for controlling RhoA degradation and regulating RhoA function in various biological contexts, which involves a Cul3/BACURD ubiquitin ligase complex.	SIGNOR-264237
P23769	Q16539	phosphorylation	up-regulates	0.269	P38_ increases gata_2 activity at endogenous target genes by inducing gata_2 multi_site phosphorylation.	SIGNOR-205242
Q12888	P25440	relocalization	up-regulates activity	0.269	BRD2 is required to recruit 53BP1 to DSBs.\|When BRD2 recruitment was blocked with shRNA or JQ1 (Fig. 3a and Supplementary Figure 3c) or a panel of BRD2 siRNAs (Supplementary Figure 3a), the recruitment of 53BP1 to DSBs was significantly delayed.	SIGNOR-262035
P63092	Q99705	binding	up-regulates activity	0.269	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-256762
Q86UE8	O14757	phosphorylation	down-regulates activity	0.269	Chk1 phosphorylates GST-fusion fragments of TLK1 in vitro.When Chk1 protein was depleted in cells transfected with pSuper-Chk1, TLK activity was not suppressed after short aphidicolin treatment of S-phase cells (Figure 8a, b).	SIGNOR-262740
Q13588	P08581	binding	up-regulates	0.269	To efficiently promote transformation met requires direct binding with grb2.	SIGNOR-42358
Q92915	Q8NEV1	phosphorylation	up-regulates activity	0.269	Bioluminescence-based screening of small molecule modulators of the FGF14:Nav1.6 complex identified 4,5,6,7 -: tetrabromobenzotriazole (TBB), a potent casein kinase 2 (CK2) inhibitor, as a strong suppressor of FGF14:Nav1.6 interaction. Inhibition of CK2 through TBB reduces the interaction of FGF14 with Nav1.6 and Nav1.2 channels. Mass spectrometry confirmed direct phosphorylation of FGF14 by CK2 at S228 and S230, and mutation to alanine at these sites modified FGF14 modulation of Nav1.6-mediated currents.	SIGNOR-275743

Q9ULW0

Q00535

0

phosphorylation

up-regulates quantity by stabilization

0.272

CDK5-mediated phosphorylation and stabilization of TPX2 promotes hepatocellular tumorigenesis

SIGNOR-265100

P04049

O60346

0

dephosphorylation

down-regulates activity

0.272

PHLPP1 and PHLPP2 dephosphorylate RAF1 to reduce its signaling, increase the invasive and migratory activities of CRC cells, and activate the epithelial-mesenchymal transition. In Apc(Min) mice, loss of PHLPP1 promotes tumor progression.

SIGNOR-237449

Q9Y4K3

P51812

0

phosphorylation

up-regulates activity

0.272

These results demonstrate that TRAF6 K63 ubiquitination might be regulated by an RSK2 mediated phosphorylation dependent mechanism and phosphorylation of TRAF6 at Ser46, 47 and 48 enhances its ubiquitin mediated inflammation signaling.

SIGNOR-278302

Q05397

Q9UQM7

0

phosphorylation

up-regulates

0.272

Furthermore, activated camkii directly phosphorylated the recombinant cooh-terminal region of fak at a residue equivalent to ser-843.

SIGNOR-135631

Q13526

P45983

0

phosphorylation

up-regulates quantity by stabilization

0.272

Mechanistically, the JNK kinases directly bind to and phosphorylate PIN1 at Ser115, and this phosphorylation prevents PIN1 mono-ubiquitination at Lys117 and its proteasomal degradation.

SIGNOR-277562

P09471

P25101

0

binding

up-regulates activity

0.272

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-257253

P26358

P49841

0

phosphorylation

down-regulates quantity

0.272

We determined that in a human lung cell line, glycogen synthase kinase 3beta (GSK3beta) phosphorylated DNMT1 to recruit beta-transducin repeat-containing protein (betaTrCP), resulting in DNMT1 degradation, and that NNK activated AKT, inhibiting GSK3beta function and thereby attenuating DNMT1 degradation.

SIGNOR-279181

P00519

Q04912

0

phosphorylation

up-regulates activity

0.272

This suggests that by interacting with Sdc4, either directly or indirectly, RON is activated via transphosphorylation when clustered, engages the ABL1 SH2 domain, and activates ABL1 by phosphorylation.

SIGNOR-272999

O43602

P49841

0

phosphorylation

up-regulates activity

0.271

Gsk3b phosphorylates dcx at the distinct site of ser327 and thereby contributes to dcx function in the restriction of axon branching. Together, our data define a jip3-regulated gsk3_/dcx signaling pathway that restricts axon branching in the mammalian brain.Gsk3_ induces the phosphorylation of dcx at ser327, which contributes to dcx function in the inhibition of axon branching and self-contact.

SIGNOR-170755

P22087

Q9NRC8

0

deacetylation

up-regulates activity

0.271

Here, we show that FBL is acetylated at several lysine residues by the acetyltransferase CBP and deacetylated by SIRT7.|hyperacetylation impairs the interaction of FBL with histone H2A and chromatin, thereby compromising H2AQ104 methylation (H2AQ104me) and rDNA transcription. SIRT7-dependent deacetylation of FBL ensures H2AQ104me and high levels of rRNA synthesis during interphase. |Global acetylome studies have shown that FBL is acetylated at four conserved lysine residues (K102, K121, K205, and K206)

SIGNOR-275894

P12235

Q06124

0

dephosphorylation

down-regulates activity

0.271

Specifically, SHP2-mediated dephosphorylation of ANT1 at Tyr 191 is essential for mitochondrial homeostasis and mitigation of NLRP3 inflammasome activation.|The interaction between SHP2 and ANT1 (Fig.\u00a0 xref ), and the opposite effects of SHP2 and ANT1 shRNAs in the activation of NLRP3 inflammasome (Figs.\u00a0 xref and xref ) raised the possibility that the SHP2 may inhibit ANT1 to suppress NLRP3 inflammasome activation.|To further determine which tyrosine phosphorylation site of ANT1 is dephosphorylated by SHP2, we created the dephosphorylated mutant of ANT1, in which tyrosine was replaced with phenylalanine (Y to F mutation).

SIGNOR-277124

Q969W9

P49910

0

transcriptional regulation

down-regulates quantity by repression

0.271

ZNF165 drives the unrestrained activation of transforming growth factor β (TGFβ) signalling by directly inactivating the expression of negative feedback pathway regulators, SMURF2, SMAD7 and PMEPA1.

SIGNOR-266094

Q96R06

P49841

0

phosphorylation

up-regulates

0.271

Astrin acts as a substrate for gsk3beta and is phosphorylated at thr-111, thr-937 ((s/t)p motif) and ser-974/thr-978 ((s/t)xxx(s/t)-p motif;p is a phosphorylatable residue). Inhibition of gsk3beta impairs spindle and kinetochore accumulation of astrin and spindle formation at mitosis, suggesting that astrin association with the spindle microtubule and kinetochore may be dependent on phosphorylation by gsk3beta

SIGNOR-159578

Q03014

Q01196

0

transcriptional regulation

up-regulates quantity

0.271

We identified Hhex as a direct target of RUNX1 and FLT3-ITD stimulation and confirmed high HHEX expression in FLT3-ITD AMLs. HHEX could replace RUNX1 in cooperating with FLT3-ITD to induce AML.

SIGNOR-256305

P0DP91

P00519

0

phosphorylation

up-regulates activity

0.271

These data raise the possibility that tyrosine phosphorylation of CSB by c-Abl promotes redistribution of CSB in the nucleus and enrichment of CSB in the nucleolus in response to oxidative stress

SIGNOR-279317

P61006

Q9BXM7

0

phosphorylation

down-regulates activity

0.271

For Rab8a, it was shown that serine 111 phosphorylation (pS111) is dependent on the protein kinase PINK1 and that mimicking the phosphorylation at S111 by a serine/glutamate substitution (S111E) impaired Rab8a activation by its cognate nucleotide exchange factor (GEF) Rabin8.

SIGNOR-260268

Q9UQD0

Q13555

0

phosphorylation

up-regulates activity

0.271

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

SIGNOR-275794

P51114

Q13153

0

phosphorylation

up-regulates activity

0.271

Identification of Ser420 in FXR1 as a PAK1 Kinase Target. During zebrafish muscle development, FXR1 Ser420 phosphorylation is needed for protein function.

SIGNOR-273713

Q86U44

P27361

0

phosphorylation

up-regulates quantity by stabilization

0.271

Mass spectrometry analysis showed that ERK phosphorylates METTL3 at three highly conserved residues: S43, S50, and S525 (Figures 2D and 2E). Mutational analysis further confirmed these three sites as main ERK phosphorylation sites (Figure 2F). Phosphorylation of METTL3 increases interaction with USP5, decreasing ubiquitination to stabilize the m6 A methyltransferase complex.

SIGNOR-265949

Q8TCJ0

Q05655

0

phosphorylation

up-regulates activity

0.271

FBXO25 encodes an orphan F-box protein that determines the substrate specificity of the SCF (SKP1-CUL1-F-box)(FBXO25) ubiquitin ligase complex. An unbiased screen uncovered the prosurvival protein HCLS1-associated protein X-1 (HAX-1) as the bona fide substrate of FBXO25 that is targeted after apoptotic stresses. Protein kinase Cdelta (PRKCD) initiates this process by phosphorylating FBXO25 and HAX-1, thereby spatially directing nuclear FBXO25 to mitochondrial HAX-1.|Accordingly, PRKCD-induced phosphorylation of Hax-1 at Ser210 and Fbxo25 at Ser178 was associated with decreased expression of Hax-1 in control cells,

SIGNOR-275561

Q14258

P12931

0

phosphorylation

up-regulates activity

0.271

Here, we demonstrated that TRIM25 interacted with c-Src and underwent tyrosine phosphorylation by c-Src kinase upon viral infection and the phosphorylation is required for the complete activation of RIG-I signaling. Analysis using a c-Src inhibitor and TRIM25 mutant, in which tyrosine 278 is substituted by phenylalanine (Y278F), suggested that the phosphorylation positively regulates K63-linked polyubiquitination of RIG-I and subsequent antiviral signaling.

SIGNOR-277405

Q00653

P49841

0

phosphorylation

down-regulates activity

0.271

More recently, phosphorylation of S707 and S711 by GSK3beta has been shown to promote complete proteasomal degradation of p100 involving the E3 ligase Fbw7 .|These studies suggest that a pool of p100 is constitutively phosphorylated by GSK3beta at S707 and S711, triggering the Fbw7 mediated ubiquitination and proteasomal degradation of p100 which controls the levels of p100 available for the non canonical pathway.

SIGNOR-279186

P43405

Q13177

0

phosphorylation

up-regulates activity

0.271

This is supported by in vitro studies showing that Pak2 phosphorylates and activates Syk.

SIGNOR-279083

O94916

Q13315

0

phosphorylation

up-regulates

0.271

Tonebp/orebp contains atm consensus phosphorylation sites at ser-1197, ser-1247, and ser-1367. In conclusion, signaling via atm is necessary for full activation of tonebp/orebp

SIGNOR-125077

P55075

P40424

0

transcriptional regulation

down-regulates quantity by repression

0.271

Our results in ES cells suggest that Engrailed inhibits Fgf8 expression in the absence of Pbx1. We identified single Engrailed- and Pbx-binding sites in the Fgf8 intron that inhibit expression of Fgf8 in mouse ES cells, but that together can allow full Fgf8 expression. Our data support the model that Engrailed heterodimerized with Pbx might activate transcription, while Engrailed or Pbx proteins alone might repress transcription

SIGNOR-265803

P38405

P37288

0

binding

up-regulates activity

0.271

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-256948

P20138

P06239

0

phosphorylation

up-regulates

0.271

Human cd33 has two tyrosine residues in its cytoplasmic domain (y340 and y358). When phosphorylated, these tyrosines could function as docking sites for the phosphatases, shp-1 and/or shp-2, enabling cd33 to function as an inhibitory receptor. Lck is effective at phosphorylating y340

SIGNOR-78960

Q07866

P28482

0

phosphorylation

down-regulates

0.271

Phosphorylation of kinesin light chain 1 at serine 460 modulates binding and trafficking of calsyntenin-1mutation of klc1ser460 to an alanine residue, to preclude phosphorylation, increased the binding of calsyntenin-1, whereas mutation to an aspartate residueklc1ser460 is a predicted mitogen-activated protein kinase (mapk) target site, and we show that extracellular-signal-regulated kinase (erk) phosphorylates this residue in vitro.

SIGNOR-172638

Q14004

P22674

0

binding

up-regulates activity

0.271

Cyclin O promotes lung cancer progression and cetuximab resistance via cell cycle regulation and CDK13 interaction|CCNO promoted tumor cell proliferation and survival in vivo via CDK13|

SIGNOR-275618

Q99683

Q14680

0

phosphorylation

up-regulates activity

0.271

MELK, as an upstream kinase of ASK1, phosphorylates threonine 838 in an activation loop of human ASK1, thereby stimulating ASK1 kinase activity.

SIGNOR-280039

Q03468

P00519

0

phosphorylation

up-regulates activity

0.271

N-terminal region of CSB interacts with the SH3 domain of c-Abl in vitro and in vivo. In addition, c-Abl kinase phosphorylates CSB at Tyr932. our results suggest that c-Abl interacts with and tyrosine phosphorylates CSB. This interaction may play an important role in the response to oxidative stress, resulting in activation of c-Abl, tyrosine phosphorylation of CSB and more efficient BER of oxidative DNA damage. Tyrosine-phosphorylated CSB may serve as a signal for repair proteins to localize to DNA damage and may help maintain active transcription in the nucleolus.

SIGNOR-251933

P04049

P62136

0

dephosphorylation

up-regulates activity

0.271

We have identified a complex comprised of Shoc2/Sur-8 and the catalytic subunit of protein phosphatase 1 (PP1c) as a highly specific M-Ras effector. M-Ras targets Shoc2-PP1c to stimulate Raf activity by dephosphorylating the S259 inhibitory site of Raf proteins

SIGNOR-251649

Q09472

Q9UPU5

0

deubiquitination

up-regulates quantity by stabilization

0.271

In this study, several cancer-related proteins (Bax, p300, E2F4 and securin) have been proven to be substrates of ubiquitin-specific peptidase 24 (USP24), and relevance has been shown between USP24 and its substrates in samples from clinical lung cancer patients. |Knockdown of USP24 decreases Bax and p300 levels

SIGNOR-275607

P12931

Q92945

0

post transcriptional regulation

up-regulates quantity by expression

0.271

We show here that this component of the DCS complex is hnRNP H and that, like hnRNP F and KSRP, hnRNP H is needed for src N1 splicing in vitro.

SIGNOR-261274

P31749

P31152

0

phosphorylation

up-regulates activity

0.271

Mechanistically, MAPK4 directly bound and activated AKT by phosphorylation of the activation loop at threonine 308.

SIGNOR-275450

Q8WZ42

P17252

0

phosphorylation

up-regulates activity

0.271

In summary, titin is a PKC substrate with PKCalpha phosphorylating predominately the full-length titin molecule.|Mechanical experiments with skinned LV myocardium revealed that PKCalpha significantly increases titin based passive tension, an effect that is reversed by PP1.

SIGNOR-278382

Q9UI12

Q92544

0

binding

up-regulates activity

0.271

Here, we demonstrate that TM9SF4 represents a novel V-ATPase-associated protein involved in V-ATPase activation. We have observed in HCT116 and SW480 colon cancer cell lines that TM9SF4 interacts with the ATP6V1H subunit of the V-ATPase V1 sector. Suppression of TM9SF4 with small interfering RNAs strongly reduces assembly of V-ATPase V0/V1 sectors, thus reversing tumor pH gradient with a decrease of cytosolic pH, alkalization of intracellular vesicles and a reduction of extracellular acidity.

SIGNOR-266885

Q9BRS8

P08670

0

binding

up-regulates activity

0.271

Interaction of LARP6 with vimentin.Here, we report that vimentin filaments associate with collagen mRNAs in a 5'SL- and LARP6-dependent manner and stabilize collagen mRNAs. LARP6 interacts with vimentin filaments through its La domain and colocalizes with the filaments in vivo.

SIGNOR-277624

P51665

Q05086

0

ubiquitination

down-regulates quantity by destabilization

0.271

Our experiments collectively suggest that UBE3A stimulates Wnt pathway activation by interacting with, ubiquitinating, and reducing the levels of multiple (PSMB1, PSMC2, PSMD2, and PSMD7) proteasome subunits.

SIGNOR-265134

P42566

Q93008

0

deubiquitination

down-regulates activity

0.271

We identify the endocytic protein Eps15 as one of the critical substrates of USP9X

SIGNOR-245052

P40763

Q15678

0

dephosphorylation

down-regulates activity

0.271

Moreover, dephosphorylation of STAT3 by PTPN14 might occur in the cytoplasm but not in nucleus.|The tyrosine phosphatase PTPN14 inhibits the activation of STAT3 in PEDV infected Vero cells.

SIGNOR-277088

Q9NPH5

P06241

0

phosphorylation

down-regulates activity

0.271

We found that direct phosphorylation of tyrosine 566 on NOX4 was critical for this FYN-mediated negative regulation.

SIGNOR-277273

Q9UGL1

Q16665

0

transcriptional regulation

up-regulates quantity by expression

0.271

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-271563

Q9Y4P8

Q8TEV9

0

transcriptional regulation

up-regulates quantity

0.271

Global mRNA expression analysis revealed that SMCR8 regulates transcription of several other autophagy genes including WIPI2

SIGNOR-252028

P10636-2

Q02156

0

phosphorylation

down-regulates activity

0.271

We have studied the relationship between the phosphorylation oftau by several kinases (MARK, PKA, MAPK, GSK3) and its assembly into PHFs. By contrast, MARK and PKA phosphorylate several sites within the repeats (notably theKXGS motifs including Ser262, Ser324, and Ser356, plus Ser320); in addition PKA phosphorylates somesites in the flanking domains, notably Ser214. This type of phosphorylation strongly reduces tau’s affinityfor microtubules, and at the same time inhibits tau’s assembly into PHFs.

SIGNOR-275444

P49841

Q05655

0

phosphorylation

down-regulates activity

0.271

In the TFEB activation pathway, activated PKC\u03b4 phosphorylates and inactivates GSK3\u03b2, leading to the reduced phosphorylation of TFEB at Ser134 and Ser138 residues; this reduced phosphorylation is critical for the cytoplasmic sequestration of TFEB.|In the TFEB activation pathway, activated PKCdelta phosphorylates and inactivates GSK3beta, leading to the reduced phosphorylation of TFEB at Ser134 and Ser138 residues; this reduced phosphorylation is critical for the cytoplasmic sequestration of TFEB.

SIGNOR-280084

P63096

Q8IYL9

0

binding

up-regulates activity

0.271

GPR65 is playing a critical role in phagocytic cells that require high levels of V-ATPase activity to maintain phagosomal and lysosomal pH, and this activity aids in the direct clearance of enteric pathogens.

SIGNOR-272502

Q13188

Q9Y243

0

phosphorylation

down-regulates

0.271

Akt phosphorylates mst2 at thr117 in vitro and in vivo, which leads to mst2 cleavage and kinase activity as well as nuclear translocation.

SIGNOR-164306

P78527

P07949

0

phosphorylation

up-regulates activity

0.27

Phosphorylation of DNA-PKcs at s2056 is elevated in RET expressing cells and can be reduced by RET inhibition.

SIGNOR-279275

P12830

P48730

0

phosphorylation

down-regulates activity

0.27

Casein kinase 1 is a novel negative regulator of E-cadherin-based cell-cell contacts|CK1 colocalizes with E-cadherin and phosphorylates the cytoplasmic domain of E-cadherin in vitro and in a cell culture system. We show that the major CK1 phosphorylation site of E-cadherin is serine 846

SIGNOR-274046

Q92915

P67870

0

phosphorylation

up-regulates activity

0.27

Bioluminescence-based screening of small molecule modulators of the FGF14:Nav1.6 complex identified 4,5,6,7 -: tetrabromobenzotriazole (TBB), a potent casein kinase 2 (CK2) inhibitor, as a strong suppressor of FGF14:Nav1.6 interaction. Inhibition of CK2 through TBB reduces the interaction of FGF14 with Nav1.6 and Nav1.2 channels. Mass spectrometry confirmed direct phosphorylation of FGF14 by CK2 at S228 and S230, and mutation to alanine at these sites modified FGF14 modulation of Nav1.6-mediated currents.

SIGNOR-275745

P22087

Q92793

0

acetylation

down-regulates activity

0.27

Here, we show that FBL is acetylated at several lysine residues by the acetyltransferase CBP and deacetylated by SIRT7.|hyperacetylation impairs the interaction of FBL with histone H2A and chromatin, thereby compromising H2AQ104 methylation (H2AQ104me) and rDNA transcription. SIRT7-dependent deacetylation of FBL ensures H2AQ104me and high levels of rRNA synthesis during interphase. |Global acetylome studies have shown that FBL is acetylated at four conserved lysine residues (K102, K121, K205, and K206)

SIGNOR-275897

Q8WYQ5

Q13315

0

phosphorylation

up-regulates quantity by stabilization

0.27

Specifically, radiation-induced ATM-dependent phosphorylation of DGCR8 at serine 677 facilitates USP51 to bind, deubiquitinate, and stabilize DGCR8, which leads to the recruitment of DGCR8 and DGCR8's binding partner RNF168 to MDC1 and RNF8 at DSBs.

SIGNOR-277307

Q9BQQ3

P28482

0

phosphorylation

down-regulates activity

0.27

Here we show that GRASP65 is phosphorylated on serine 277 in interphase cells, and this is strongly enhanced in response to the addition of serum or epidermal growth factor. This is directly mediated by ERK suggesting that GRASP65 has some role in growth factor signal transduction. These results argue against Ser-277 phosphorylation alone causing the dissolution of GRASP65 oligomers and cisternal unstacking, although it may make a significant contribution to these events.

SIGNOR-262841

P81274

Q96KB5

0

phosphorylation

up-regulates

0.27

We found that the 450th threonine (thr450) of lgn/gpsm2 was phosphorylated by the serine/threonine kinase pbk/topk during mitosis. Western blot analysis indicated the highest expression and the phosphorylated form of lgn/gpsm2 protein in g2/m phase.

SIGNOR-166461

P06213

Q9HD43

0

dephosphorylation

down-regulates

0.27

These results, combined with secondary dephosphorylation tests, confirm and extend earlier findings that ptp-1b and t-cell ptp are physiological enzymes for the insulin receptor kinase

SIGNOR-76072

O14672

P22415

0

transcriptional regulation

up-regulates quantity by expression

0.27

The promoter region of ADAM10 contains several transcription factor binding sites that can stimulate its transcription. These include binding sites for transcription factors SP1 and USF, and the spliced form of the X-box binding protein (XBP)-1 as well as a retinoic acid-responsive element

SIGNOR-259837

P08670

Q00535

0

phosphorylation

up-regulates activity

0.27

Cdk5 mediates vimentin Ser56 phosphorylation during GTP-induced secretion by neutrophils.

SIGNOR-278922

P08908

Q00535

0

phosphorylation

down-regulates quantity by destabilization

0.27

Cyclin-dependent kinase 5 promotes proteasomal degradation of the 5-HT 1A receptor via phosphorylation|5-HT1AR was phosphorylated by the Cdk5-p35 complex at Thr314 in the third cytoplasmic loop.

SIGNOR-264406

Q8ND25

P00533

0

phosphorylation

up-regulates activity

0.27

Together, these results demonstrate that EGFR-dependent phosphorylation of ZNRF1 at Y103 promotes degradation of AKT and resultant activation of GSK3\u03b2, which mediates oxidative stress\u2013induced neuronal apoptosis ( xref ).

SIGNOR-279522

P19086

P43115

0

binding

up-regulates activity

0.27

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-257111

P08151

Q16539

0

phosphorylation

down-regulates quantity by destabilization

0.27

Here, we show that SHH inactivates p38α (MAPK14) in a smoothened-dependent manner, conversely, p38α directly phosphorylates GLI1 on Ser937/Ser941 (human/mouse) to induce GLI1's proteasomal degradation and negates the transcription of SHH signaling.

SIGNOR-277916

P53805

P28482

0

phosphorylation

up-regulates activity

0.27

Consensus phosphorylation sites for p42/44 MAPK and GSK-3 are present in the SP repeat of MCIP1 at serine 112 and serine 108, respectively |Several endogenous proteins are capable of inhibiting the catalytic activity of calcineurin. Modulatory calcineurin interacting protein 1 (MCIP1) is unique among these proteins on the basis of its pattern of expression and its function in a negative feedback loop to regulate calcineurin activity. Here we show that MCIP1 can be phosphorylated by MAPK and glycogen synthase kinase-3 and that phosphorylated MCIP1 is a substrate for calcineurin.

SIGNOR-249198

P38405

P32245

0

binding

up-regulates activity

0.27

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-256940

P20719

O15550

0

transcriptional regulation

up-regulates quantity by expression

0.27

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-260023

P37840

P53355

0

phosphorylation

up-regulates quantity

0.27

We demonstrated that DAPK1 directly phosphorylates \u03b1-synuclein at Ser129, and induces the formation of insoluble \u03b1-synuclein aggregates.

SIGNOR-278440

P49662

Q63HK5

0

transcriptional regulation

down-regulates quantity by repression

0.27

Chromatin immunoprecipitation showed a direct interaction of FE65 and Teashirt3 with the promoter region of CASP4. The results were consistent with a model in which reduced expression of Teashirt3, mediated by genetic or other causes, increases caspase-4 expression, leading to progression of AD.

SIGNOR-264815

P10636-2

P05129

0

phosphorylation

down-regulates activity

0.27

We have studied the relationship between the phosphorylation oftau by several kinases (MARK, PKA, MAPK, GSK3) and its assembly into PHFs. By contrast, MARK and PKA phosphorylate several sites within the repeats (notably theKXGS motifs including Ser262, Ser324, and Ser356, plus Ser320); in addition PKA phosphorylates somesites in the flanking domains, notably Ser214. This type of phosphorylation strongly reduces tau’s affinityfor microtubules, and at the same time inhibits tau’s assembly into PHFs.

SIGNOR-275445

O60716

P28482

0

phosphorylation

down-regulates activity

0.27

Upon TGFβ treatment, activated extracellular signal-regulated kinase 1/2 (ERK1/2) phosphorylates T900 of p120-catenin to promote its interaction with Smurf1 and subsequent monoubiquitination. TGFβ promotes monoubiquitination of p120-catenin through Smurf1 to induce junction dissociation.

SIGNOR-277505

P48167

P12931

0

phosphorylation

up-regulates

0.27

These findings indicate that glyr function is upregulated by ptks and this modulation is dependent on the tyrosine-413 residue of the beta subunit.

SIGNOR-115705

P19338

P60484

0

dephosphorylation

up-regulates activity

0.27

The fact that PTEN\u03b2 interacts with nucleolin and dephosphorylates nucleolin at Thr84 raised a question as to whether nucleolin mediates PTEN\u03b2 regulation of rDNA transcription, and thus represents a direct mechanism by which PTEN\u03b2 controls ribosomal biogenesis.

SIGNOR-277166

Q13114

Q96PU5

0

ubiquitination

up-regulates activity

0.27

Nedd4l promotes TRAF3 to interact with cIAP1/2 and HECTD3.|Ubiquitination of TRAF3 by Nedd4l promotes interaction of TRAF3 with proteins such as cIAP1/2, HECTD3, and TBK1.

SIGNOR-278587

Q12756

P0DP25

0

binding

up-regulates activity

0.27

To better understand how KIF1A-driven dense core vesicle (DCV) transport is regulated, we identified the KIF1A interactome and focused on three binding partners, the calcium binding protein calmodulin (CaM) and two synaptic scaffolding proteins: liprin-α and TANC2. We showed that calcium, acting via CaM, enhances KIF1A binding to DCVs and increases vesicle motility. In contrast, liprin-α and TANC2 are not part of the KIF1A-cargo complex but capture DCVs at dendritic spines. we can conclude that TANC2 and liprin-α are enriched in dendritic spines and interact with various synaptic proteins. TANC2 and Liprin-α2 Act as Immobile Postsynaptic Posts Able to Recruit KIF1A in a Subset of Dendritic Spines

SIGNOR-266890

Q2M2I8

Q15208

0

phosphorylation

up-regulates activity

0.27

We identified 5 potential NDR1 substrates in the mouse brain and chose two for functional validation. We show that one NDR1 substrate is another kinase, AP-2 associated kinase-1 (AAK1) which regulates dendritic branching as a result of NDR1 phosphorylation. Another substrate is the Rab8 guanine nucleotide exchange factor (GEF) Rabin8 (a Sec2p homolog) which we find is involved in spine synapse formation. AAK1 phosphorylation regulates dendrite branching and length

SIGNOR-263034

P46531

P11309

0

phosphorylation

up-regulates activity

0.27

Interestingly, Pim1 phosphorylated Notch1 and Notch3, but not Notch2 ICD (Figure xref ), which was in line with the observed Pearson correlations ( xref ).|Our data indicate that endogenous Pim1 and Notch1 interact already in the cytoplasm, which supports the notion that Pim1 enhances nuclear localization and activity of Notch1.

SIGNOR-279643

P78352

P35637

0

post transcriptional regulation

up-regulates quantity

0.27

These results point toward a novel mechanism by which FUS targets neuronal mRNA and given that these PSD-95 and Shank1 3'-UTR G quadruplex structures are also targeted by the fragile X mental retardation protein (FMRP), they raise the possibility that FUS and FMRP might work together to regulate the translation of these neuronal mRNA targets.|As seen in Figure 7 (top panel), both PSD-95 Q1-Q2 and Shank1a GQ probes pulled down endogenous FUS, whereas their M2 mutants did not, indicating that the GQ structure is sufficient for recognition.

SIGNOR-262103

Q02750

O15530

0

phosphorylation

up-regulates activity

0.27

In vitro kinase assay revealed that the direct targets of pdk1 in the mapk pathway were the upstream mapk kinases mek1 and mek2. The identified pdk1 phosphorylation sites in mek1 and mek2 are ser222 and ser226, respectively, and are known to be essential for full activation

SIGNOR-236633

P32754

A6NLP5

0

binding

up-regulates quantity by stabilization

0.27

Decreased expression of 4-hydroxyphenylpyruvic acid dioxygenase (HPD), a key enzyme for tyrosine metabolism, is a cause of human tyrosinemia. However, the regulation of HPD expression remains largely unknown. Here, we demonstrate that molecular chaperone TTC36, which is highly expressed in liver, is associated with HPD and reduces the binding of protein kinase STK33 to HPD, thereby inhibiting STK33-mediated HPD T382 phosphorylation. The reduction of HPD T382 phosphorylation results in impaired recruitment of FHA domain-containing PELI1 and PELI1-mediated HPD polyubiquitylation and degradation.

SIGNOR-272960

O60716

P07333

0

phosphorylation

up-regulates quantity by stabilization

0.27

In our study, CSF-1R induced the tyrosine phosphorylation of p120 Y904 and Y228 in a SRC-dependent manner ( xref ).

SIGNOR-278929

O95466

Q05655

0

phosphorylation

up-regulates activity

0.27

PKC\u03b4 induces FMNL1 phosphorylation.

SIGNOR-279261

O60566

Q96SN8

0

transcriptional regulation

up-regulates quantity by expression

0.27

These data indicate that CDK5RAP2 is a positive regulator of both the BUBR1 promoter and the MAD2 promoter

SIGNOR-260312

P08581

P51608

0

post transcriptional regulation

down-regulates quantity by repression

0.27

MeCP2 binding enhances MET expression in the presence of the rs1858830 C allele, but MET transcription is attenuated by RTT-specific mutations in MeCP2

SIGNOR-264683

P20749

P31751

0

phosphorylation

up-regulates quantity by stabilization

0.27

Here we show that Akt, Erk2, and IKK1/2 phosphorylate Bcl3. Phosphorylation of Ser33 by Akt induces switching of K48 ubiquitination to K63 ubiquitination and thus promotes nuclear localization and stabilization of Bcl3. Phosphorylation by Erk2 and IKK1/2 of Ser114 and Ser446 converts Bcl3 into a transcriptional coregulator by facilitating its recruitment to DNA.

SIGNOR-277359

Q15021

P51955

0

phosphorylation

down-regulates activity

0.269

Nek2 phosphorylates C-Nap1, rootletin and beta-catenin to regulate centrosome separation.

SIGNOR-279234

Q15139

Q05655

0

phosphorylation

up-regulates

0.269

Here we show that activation of pkd in response to oxidative stress requires two sequential signaling events, i.e., phosphorylation of tyr463 by abl, which in turn promotes a second step, phosphorylation of the pkd activation loop (ser738/ser742). We show that this is mediated by pkcdelta (protein kinase cdelta)

SIGNOR-123453

Q06413

Q32MK0

0

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

Q13315

P62714

0

dephosphorylation

down-regulates activity

0.269

Ionizing radiation induces autophosphorylation of the ataxia-telangiectasia mutated (ATM) protein kinase on serine 1981; however, the precise mechanisms that regulate ATM activation are not fully understood. Here, we show that the protein phosphatase inhibitor okadaic acid (OA) induces autophosphorylation of ATM on serine 1981 in unirradiated cells at concentrations that inhibit protein phosphatase 2A-like activity in vitro.

SIGNOR-248601

P19086

P21728

0

binding

up-regulates activity

0.269

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-257269

P37802

P28482

0

phosphorylation

up-regulates quantity by stabilization

0.269

ERK2 interacted with 29-31 amino acids of transgelin-2 and subsequently phosphorylated the S145 residue of transgelin-2. S145 phosphorylation of transgelin-2 played important roles in cell proliferation and tumorigenesis of PDAC.| We found that the protein stability of transgelin-2 was regulated by KRAS. ERK-mediated phosphorylation resulted in accumulation of transgelin-2 protein.

SIGNOR-265221

Q92915

P68400

0

phosphorylation

up-regulates activity

0.269

Bioluminescence-based screening of small molecule modulators of the FGF14:Nav1.6 complex identified 4,5,6,7 -: tetrabromobenzotriazole (TBB), a potent casein kinase 2 (CK2) inhibitor, as a strong suppressor of FGF14:Nav1.6 interaction. Inhibition of CK2 through TBB reduces the interaction of FGF14 with Nav1.6 and Nav1.2 channels. Mass spectrometry confirmed direct phosphorylation of FGF14 by CK2 at S228 and S230, and mutation to alanine at these sites modified FGF14 modulation of Nav1.6-mediated currents.

SIGNOR-275738

Q01196

P11309

0

phosphorylation

up-regulates activity

0.269

Furthermore, catalytically active Pim-1 kinase was able to phosphorylate Runx1 and Runx3 proteins and enhance the transactivation activity of Runx1 in a dose-dependent fashion.|Pim-1 potentiates transcriptional activity of the RUNX1 transcription factor.

SIGNOR-278976

P49715

Q15466

0

binding

down-regulates activity

0.269

SHP repressed C/EBPalpha (CCAAT/enhancer-binding protein alpha)-driven transcription of PEPCK through direct interaction with C/EBPalpha protein both in vitro and in vivo. The formation of an active transcriptional complex of C/EBPalpha and its binding to DNA was inhibited by SHP, resulting in the inhibition of PEPCK gene transcription.

SIGNOR-254831

P35580

Q05513

0

phosphorylation

down-regulates

0.269

After egf stimulation, apkc_ translocates from the nucleus to the cytoplasm (figure 3) and is therefore able to interact with myosin ii-b. apkc_ phosphorylates nmhc ii-b on ser1937, which is located on the nonhelical tailpiece, leading to filament disassembly at certain sites of the cell

SIGNOR-146100

P61586

Q9H3F6

0

binding

down-regulates quantity

0.269

BACURDs form ubiquitin ligase complexes, which selectively ubiquitinate RhoA, with Cul3. Our studies reveal a previously unknown mechanism for controlling RhoA degradation and regulating RhoA function in various biological contexts, which involves a Cul3/BACURD ubiquitin ligase complex.

SIGNOR-264237

P23769

Q16539

0

phosphorylation

up-regulates

0.269

P38_ increases gata_2 activity at endogenous target genes by inducing gata_2 multi_site phosphorylation.

SIGNOR-205242

Q12888

P25440

0

relocalization

up-regulates activity

0.269

BRD2 is required to recruit 53BP1 to DSBs.|When BRD2 recruitment was blocked with shRNA or JQ1 (Fig. 3a and Supplementary Figure 3c) or a panel of BRD2 siRNAs (Supplementary Figure 3a), the recruitment of 53BP1 to DSBs was significantly delayed.

SIGNOR-262035

P63092

Q99705

0

binding

up-regulates activity

0.269

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-256762

Q86UE8

O14757

0

phosphorylation

down-regulates activity

0.269

Chk1 phosphorylates GST-fusion fragments of TLK1 in vitro.When Chk1 protein was depleted in cells transfected with pSuper-Chk1, TLK activity was not suppressed after short aphidicolin treatment of S-phase cells (Figure 8a, b).

SIGNOR-262740

Q13588

P08581

0

binding

up-regulates

0.269

To efficiently promote transformation met requires direct binding with grb2.

SIGNOR-42358

Q92915

Q8NEV1

0

phosphorylation

up-regulates activity

0.269

Bioluminescence-based screening of small molecule modulators of the FGF14:Nav1.6 complex identified 4,5,6,7 -: tetrabromobenzotriazole (TBB), a potent casein kinase 2 (CK2) inhibitor, as a strong suppressor of FGF14:Nav1.6 interaction. Inhibition of CK2 through TBB reduces the interaction of FGF14 with Nav1.6 and Nav1.2 channels. Mass spectrometry confirmed direct phosphorylation of FGF14 by CK2 at S228 and S230, and mutation to alanine at these sites modified FGF14 modulation of Nav1.6-mediated currents.

SIGNOR-275743