GleghornLab/Signor_2class · Datasets at Hugging Face

IdA string	IdB string	labels int64	mechanism string	effect string	score float64	sentence string	signor_id string
P17612	P30305	1	phosphorylation	up-regulates activity	0.2	Overall, PRKACA may directly phosphorylate CDC25B on Ser321 to control cell cycle progression in mouse-fertilized eggs [ xref ].\|PRKACA phosphorylates and activates CDC25B in fertilized eggs of mice [ xref ].	SIGNOR-280077
Q12981	Q96GF1	0	polyubiquitination	up-regulates activity	0.533	RNF185 functions as a ubiquitin E3 ligase, enabling BNIP1-p62 interaction. Here we show that human RNF185 is a mitochondrial ubiquitin E3 ligase that regulates selective mitochondrial autophagy in cultured cells. Human BNIP1 colocalizes with RNF185 at mitochondria and is polyubiquitinated by RNF185 through K63-based ubiquitin linkage in vivo. The polyubiquitinated BNIP1 is capable of recruiting autophagy receptor p62, which simultaneously binds both ubiquitin and LC3 to link ubiquitination and autophagy. RNF185 interacts with BNIP1 and ATG5	SIGNOR-271931
P63279	O75030	1	ubiquitination	down-regulates	0.565	Furthermore, we identified lysine 201 as a potential ubiquitination site. A lysine to arginine mutation abolished mitf (k201r) degradation by hubc9 in vivo.	SIGNOR-75117
Q99683	P31749	0	phosphorylation	down-regulates activity	0.729	Akt phosphorylates and negatively regulates apoptosis signal-regulating kinase 1 akt decreased ask1 kinase activity stimulated by both oxidative stress and overexpression in 293 cells by phosphorylating a consensus akt site at serine 83 of ask1.	SIGNOR-252465
P17252	P08567	1	phosphorylation	up-regulates	0.28	To determine the role of pkc-dependent phosphorylation in pleckstrin function, we mapped the phosphorylation sites in vivo of wild-type and site-directed mutants of pleckstrin expressed in cos cells. Phosphorylation was found to occur almost exclusively on ser-113 and ser-117. Replacing all these sites with glycine decreased phosphorylation by > 90% and reduced pleckstrin's ability to inhibit phosphoinositide hydrolysis by as much as 80%.	SIGNOR-40048
O75807	P18848	0	transcriptional regulation	up-regulates quantity by expression	0.657	ATF4 also induces another bZIP protein C/EBP-homologous protein (CHOP), which is responsible for triggering apoptosis in cells under prolonged ER stress. ATF4 and CHOP further induce growth arrest and DNA damage–inducible protein 34 (GADD34),a regulatory subunit of protein phosphatase 1 (PP1) that dephosphorylates eIF2α. This negative feedback mechanism enables protein synthesis to resume after resolution of ER stress.	SIGNOR-260172
P51955	Q13188	0	phosphorylation	up-regulates	0.244	Our data suggest that mst2 phosphorylates nek2a thereby recruiting nek2a to centrosomes and promoting phosphorylation and displacement of centrosomal linker proteins	SIGNOR-169539
P23769	O60216	0	relocalization	down-regulates activity	0.325	Large-scale AML genome re-sequencing efforts have identified novel recurrently mutated genes, including the members of the cohesin complex (RAD21, SMC3, SMC1A, and STAG2), implicated in the pathogenesis of this disease.Using ATAC-seq, we determined that mutant cohesin lead to a state of elevated chromatin accessibility and higher predicted binding at transcription factor binding sites for ERG, GATA2, and RUNX1. Moreover, using ChIP-Seq, we formally demonstrated increased binding of GATA2 and RUNX1 to these sites. Finally, we demonstrated that knockdown of these three TFs in human HSPC can revert the differentiation block induced by mutant cohesin. These results support a model in which mutant cohesin impairs hematopoietic differentiation and enforces stem cell programs through the modulation of ERG, GATA2, and RUNX1 chromatin accessibility, expression, and activity.	SIGNOR-261513
P63000	Q17R89	0	gtpase-activating protein	down-regulates activity	0.589	We therefore developed a screening-compatible live-cell imaging assay, using FRET-based biosensors for the prototype GTPases RHOA, RAC1 and CDC4215,19,20 (Extended Data Fig. 2 and Supplementary Note 1)\|We found catalytic activities for 45/75 RhoGEFs and 48/63 RhoGAPs\| Our data thus not only reveal extensive promiscuity among regulators, but also that the inactivating RhoGAPs are less selective than the activating RhoGEFs (p-value=0.02)(Supplementary Table 2).	SIGNOR-260498
O14920	Q04206	1	phosphorylation	up-regulates activity	0.886	Rela is phosphorylated at ser536 by ikkbeta, ikkalfa, ikkepsilon, nf-kb activating kinase (nak, also known as tank-binding kinase-1 tbk1) and rsk1 (also known as p90 ribosomal protein s6 kinase (p90s6k). We now present evidence that suggests that the upstream kinase ikkbeta plays an important role in tax-induced p53 inhibition through phosphorylation of p65/rela at ser-536. Ikkbeta plays an important role in tax-induced p53 inhibition through phosphorylation of p65/rela at ser-536.	SIGNOR-138903
P17612	Q05469	1	phosphorylation	up-regulates activity	0.602	HSL activity is known to be regulated by phosphorylation (3). PKA increases HSL activity via phosphorylation at Ser563, Ser659, and Ser660 (14,15), although phosphorylation at Ser565 by glycogen synthase kinase, AMP-dependent protein kinase, or Ca2+/calmodulin-dependent protein kinase II has been reported to prevent activation of the enzyme	SIGNOR-249202
Q05655	P17096	1	phosphorylation	down-regulates	0.263	In this study, we showed that the pkc-mediated phosphorylation of hmg-i exerted a very potent inhibition on the binding of this protein to the at-rich promoter regions of both pkc g and ng genes. The purified hmg-i can be phosphorylated by pkc a,b, g, and d but is poorly phosphorylated by pkc e and z. We have mapped two major sites of phosphorylation by pkc at ser44 and ser64	SIGNOR-73610
Q96PH1	P00519	0	phosphorylation	up-regulates activity	0.303	As shown in Fig. xref and c, c-Abl-phosphorylated NOX5 was mostly inhibited when c-Abl plasmid co-transfected with NOX5 Y476/Y478F mutant, then the NOX5 Y487F mutant, but not with NOX5 Y519F mutant.\|Collectively, these results indicate that Pyk2 may act as a scaffolding protein for c-Abl stimulation of NOX5 activity in Pyk2 and NOX5 complex, and c-Abl-enhanced NOX5 activity is mainly dependent on phosphorylation of NOX5 Tyr 476/478 sites.	SIGNOR-280170
P33981	P10636	1	phosphorylation	up-regulates activity	0.2	Fig. 6C-1 shows that the GST-TTK fusion protein phosphorylated both tau and tubulin, but the phosphorylating activity on tau was much higher than that on tubulin.	SIGNOR-279132
P49356	P01116	1	null	up-regulates activity	0.419	Major investments have been made to target Ras through indirect routes. Inhibition of farnesyl transferase to block Ras maturation has failed in large clinical trials.	SIGNOR-242556
Q8TBB1	O95477	1	ubiquitination	down-regulates quantity by destabilization	0.242	We used the Ligand of Numb protein X (LNX) family of E3s, a group of PDZ domain-containing RING-type E3 ubiquitin ligases, to demonstrate the feasibility of this strategy. Many potential substrates of LNX E3s were identified. Eight of the nine selected candidates were ubiquitinated in vitro, and two novel endogenous substrates, PDZ-binding kinase (PBK) and breakpoint cluster region protein (BCR), were confirmed in vivo.	SIGNOR-272902
P07711	P59594	1	cleavage	up-regulates activity	0.2	A cell-free membrane-fusion system demonstrates that engagement of receptor followed by proteolysis is required for SARS-CoV membrane fusion and indicates that cathepsin L is sufficient to activate membrane fusion by SARS-CoV S. These results suggest that SARS-CoV infection results from a unique, three-step process: receptor binding and induced conformational changes in S glycoprotein followed by cathepsin L proteolysis within endosomes. The requirement for cathepsin L proteolysis identifies a previously uncharacterized class of inhibitor for SARS-CoV infection.	SIGNOR-260218
Q9H9Q4	P31749	0	phosphorylation	down-regulates quantity by destabilization	0.358	Akt1 phosphorylates XLF at T181 Here, we report that Akt phosphorylates XLF at Thr181 to trigger its dissociation from the DNA ligase IV/XRCC4 complex, and promotes its interaction with 14-3-3β leading to XLF cytoplasmic retention, where cytosolic XLF is subsequently degraded by SCF(β-TRCP) in a CKI-dependent manner.	SIGNOR-276881
Q16539	P45985	0	phosphorylation	up-regulates activity	0.591	Two human MAP kinase kinases (MKK3 and MKK4) were cloned that phosphorylate and activate p38 MAP kinase.	SIGNOR-34121
Q16539	Q13541	1	phosphorylation	down-regulates activity	0.433	4E-BP1 Is Phosphorylated in Vitro by Active p38 Kinase. In the present study we demonstrated that UVB induced 4E-BP1 phosphorylation at multiple sites, Thr-36, Thr-45, Ser-64, and Thr-69, leading to dissociation of 4E-BP1 from eIF-4E.	SIGNOR-250097
Q00535	Q16555	1	phosphorylation	down-regulates activity	0.655	Cdk5 and DYRK2 phosphorylate CRMP2 and CRMP4, respectively, priming these proteins at S522 before their subsequent phosphorylation by GSK-3b at T509, T516 and S518\|e CRMP2 phosphorylation by GSK-3b disrupts its interaction with tubulin (Yamashita & Goshima, 2012), leading to growth inhibition	SIGNOR-264838
Q9HCE7	P31749	0	phosphorylation	up-regulates activity	0.352	Furthermore, phosphorylation of Smurf1 by Akt1 was carried out specifically on the T145 residue, as mutation of this site abolished recognition of Smurf1 by the Akt1 phosphorylation motif antibody (Figure 5D).\|We also identified that Smurf1 itself is targeted for phosphorylation by Akt1 and Akt2, regulating its stability.	SIGNOR-279778
Q15910	P24941	0	phosphorylation	up-regulates activity	0.547	Here, we demonstrate that the phosphorylation of EZH2 by cyclin-dependent kinases at Thr416 creates a docking site for the ForkHead-associated domain of NIPP1.	SIGNOR-255656
P54646	P17612	0	phosphorylation	down-regulates	0.42	Pka associates with and phosphorylates ampk?1 At ser-173 to impede threonine thr-172 phosphorylation and thus activation of ampk1 by lkb1 in response to lipolytic signals	SIGNOR-161860
P14598	P31749	0	phosphorylation	up-regulates	0.559	Akt phosphorylates p47phox and mediates respiratory burst activity in human neutrophils. A direct interaction between p47(phox) and akt was shown. Active recombinant akt phosphorylated recombinant p47(phox) in vitro. Mutation analysis indicated that 2 aa residues, ser(304) and ser(328), were phosphorylated by akt. Inhibition of akt activity also inhibited fmlp-stimulated neutrophil chemotaxis.	SIGNOR-252586
P49841	Q00613	1	phosphorylation	down-regulates activity	0.557	Ser-303 is phosphorylated by glycogen synthase kinase 3 (GSK3) through a mechanism dependent on primary phosphorylation of Ser-307 by MAPK. Secondary phosphorylation of Ser-303 by GSK3 may thus repress the activity of HSF-1, and its requirement for priming by MAPK phosphorylation of Ser-307 provides a potential link between the MAPK cascade and HSF-1.	SIGNOR-251216
Q8WXD9	P54762	0	phosphorylation	up-regulates activity	0.283	EphB1 phosphorylates Caskin1 on tyrosine 296 and 336. Tyrosine phosphorylated Caskin1 then likely promotes reorganization of the actin cytoskeleton leading to spine formation.	SIGNOR-262861
P37231	P00519	0	phosphorylation	up-regulates quantity	0.341	We show that the tyrosine kinase Abelson murine leukemia viral oncogene (cAbl) is an adipogenic key regulator. c-Abl promotes adipogenesis by phosphorylation and subsequent stabilization of PPARγ.	SIGNOR-262297
P17252	P13498	1	phosphorylation	up-regulates	0.2	Phosphorylation of p22phox on threonine 147 enhances NADPH oxidase activity by promoting p47phox binding. \| Threonine 147 of p22phox Is Phosphorylated by PKC-α and PKC-δ in Vitro	SIGNOR-260891
Q9UPU5	Q13315	0	phosphorylation	up-regulates activity	0.25	Taken together, these data suggest that the ATM kinase mediated phosphorylation of USP24 is involved in USP24 stabilization/up regulation following UV irradiation.\|Taken together, these data suggest that the ATM kinase-mediated phosphorylation of USP24 is involved in USP24 stabilization/up-regulation following UV irradiation.	SIGNOR-280043
P23470	P08581	1	dephosphorylation	down-regulates activity	0.317	PTPRG activation by the P1-WD peptide affected the tyrosine phosphorylation of several signaling molecules. Data analysis identified 31 molecules whose phosphorylation was modified in a statistically significant manner (Table I). inhibition of ABL1, BMX, BTK, DAB1, ITGB1, JAK2, KDR, KIT, LIMK1, MET, PDGFRB, SHC1, and VCL correlates with tyrosine dephosphorylation. In contrast, SRC inhibition correlates with hyperphosphorylation of the inhibitory Tyr530 residue and with dephosphorylation of the activatory Tyr419. Moreover, CDK2 and CTTN inhibition correlates with a hyperphosphorylation of the inhibitory Tyr15 and Tyr470, respectively. In contrast, a subgroup of 13 proteins, including BLNK, DOK2, ERBB2, GRIN2B, INSR, PDGFRA, PRKCD, PXN, STAT1, STAT2, STAT3, STAT5A, and ZAP70, appears to be activated by PTPRG activity.	SIGNOR-254712
P15336	P45984	0	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
Q14676	Q13315	0	phosphorylation	up-regulates	0.846	We show that, in response to ionizing radiation, mdc1 is hyperphosphorylated in an atm-dependent manner, and rapidly relocalizes to nuclear foci that also contain the mre11 complex, phosphorylated histone h2ax and 53bp1.	SIGNOR-98798
P20393	O00327	1	transcriptional regulation	down-regulates quantity by repression	0.671	In this study, we found that NPAS2, like BMAL1, is a direct target gene of RORα and REV-ERBα. it appears in the context of the NPAS2 promoter RORα functions as a transcriptional activator, but REV-ERBα may only function as an inhibitor of RORα activity by blocking binding.	SIGNOR-267983
P17676	P37231	1	transcriptional regulation	up-regulates quantity	0.729	Induction of C/EBP beta DNA-binding activity in NIH-3T3 beta 2 cells exposed to dexamethasone in the presence of insulin and fetal bovine serum activates the expression of an adipocyte-specific nuclear hormone receptor, PPAR gamma, that stimulates the conversion of these fibroblasts into committed preadipocytes	SIGNOR-255730
Q16539	P10415	1	phosphorylation	down-regulates activity	0.334	Bcl-2 phosphorylation by p38 mapkin this study, we identify, by using mass spectrometry techniques and specific anti-phosphopeptide antibodies, ser(87) and thr(56) as the bcl-2 residues phosphorylated by p38 mapk and show that phosphorylation of these residues is always associated with a decrease in the antiapoptotic potential of bcl-2 protein.	SIGNOR-146786
O43684	O43683	0	relocalization	up-regulates activity	0.943	Spindle checkpoint protein Bub1 is required for kinetochore localization of Mad1, Mad2, Bub3, and CENP-E, independently of its kinase activity	SIGNOR-252019
P08581	Q14289	1	phosphorylation	up-regulates activity	0.28	In this study, using a protein array approach, we found that c-Met phosphorylates FAK and Pyk2 in medulloblastoma cells.\|Our study shows for the first time that c-Met activates FAK and Pyk2 and that FAK and Pyk2 mediate the effects of c-Met in medulloblastoma.	SIGNOR-280040
P47712	Q9BUB5	0	phosphorylation	up-regulates activity	0.577	The results suggest that MNK1 or a closely related kinase is responsible for in vivo phosphorylation of cPLA2 on Ser-727.	SIGNOR-226633
P68400	Q96FW1	1	phosphorylation	up-regulates activity	0.319	Casein kinase 2 (CK2)-dependent phosphorylation of OTUB1 at Ser16 played a critical role in ODN- and cathepsin K siRNA-mediated p53 stabilization. \|Furthermore, although OTUB1 dramatically induced p53 deubiquitination, its mutant (S16A) and deletion mutant did not have this effec	SIGNOR-276527
Q15418	P17676	1	phosphorylation	up-regulates activity	0.683	13 The data presented support previous findings that C/EBPbeta can be a molecular target of RSK1, 16 but provide the first indication that RSK1 can phosphorylate and activate C/EBPbeta to mediate the IL-6 signalling events in cholangiocarcinoma.\|As mentioned above, RSK1 has been shown to activate C/EBPbeta in hepatic stellate cells in an experimental model of liver fibrosis.	SIGNOR-280112
P46527	O15297	0	dephosphorylation	down-regulates activity	0.259	Increased expression of wildtype WIP1 reduces stability of p27 Kip1 while increased expression of similar amounts of phosphatase-dead WIP1 has no effect on p27 Kip1 protein stability.\|We demonstrate that wildtype, but not phosphatase-dead WIP1, efficiently dephosphorylates p27 Kip1 Ser140 both in vitro and in cells and that this dephosphorylation is sensitive to the WIP1 specific inhibitor GSK 2830371.	SIGNOR-277109
P68400	Q9UJY5	1	phosphorylation	down-regulates activity	0.504	Serine-355 of GGA1 is phosphorylated in vivo and in vitro. This inhibition is caused by the binding of an AC-LL sequence present in the hinge segment to the ligand-binding site in the VHS domain. The inhibition depends on the phosphorylation of a serine located three residues upstream of the AC-LL motif. The serine is phosphorylated by casein kinase 2 in in vitro assays.	SIGNOR-273623
P25963	Q9UQB9	0	phosphorylation	up-regulates activity	0.2	AURKC directly induces IkappaBalpha activation via an interaction between the two proteins, leading to phosphorylation of IkappaBalpha.\|AURKC phosphorylates IkappaBalpha on S32 and binds its ankyrin repeat domain.	SIGNOR-278470
Q9Y6Q9	P49840	0	phosphorylation	down-regulates quantity by destabilization	0.2	GSK3 Phosphorylates SRC-3 on S505.In this report, we identified GSK3 as a kinase that phosphorylates SRC-3 on S505 and demonstrated that this phosphorylation modulates SRC-3 transcriptional function and turnover.	SIGNOR-276067
Q99075	P03956	0	cleavage	up-regulates activity	0.33	We have recently reported that HB-EGF is a substrate of MT1-MMP and that removal of the N-terminal fragment of HB-EGFby MT1-MMP converts the former into a hyperactive growthfactor that does not require heparin as a co-factor.	SIGNOR-278096
P43405	P40763	1	phosphorylation	up-regulates activity	0.552	The current study indicates that the plasma cell malignancy is also associated with Syk-activated STAT3 directly downstream of reelin-induced integrin \u03b21 engagement and FAK/Src activation (Figure xref ).\|The integrin-activated spleen tyrosine kinase (Syk) was shown to promote STAT3 phosphorylation [42, 44].	SIGNOR-279298
Q13627	Q13247	1	phosphorylation	up-regulates activity	0.432	These results suggest that Dyrk1A enhances SRp55 promoted cTnT exon 5 inclusion.\|These results supported the finding that phosphorylation of SRp55 by Dyrk1A promotes cTnT exon 5 inclusion.Alternative splicing of cTnT exon 5 is regulated developmentally.	SIGNOR-279166
P51608	Q13451	1	transcriptional regulation	down-regulates quantity by repression	0.306	These results are compatible with the hypothesis that MeCP2 associates with the Sgk and Fkbp5 promoters and has a repressive effect that is over-ridden by elevated glucocorticoids in response to stress.	SIGNOR-264542
P56645	P49674	0	phosphorylation	down-regulates activity	0.74	The CKI phosphorylation of mPer1 and mPer3 proteins results in their rapid degradation, which is dependent on the ubiquitin-proteasome pathway. Moreover, CKIepsilon and CKIdelta are able to induce nuclear translocation of mPer3, which requires its nuclear localization signal. The mutation in potential phosphorylation sites on mPer3 decreased the extent of both nuclear translocation and degradation of mPer3 that are stimulated by CKIepsilon. \| In mut7 in which all of the conserved serine and threonine residues in this region were mutated, the ratio of the shifted band was greatly reduced reproducibly.	SIGNOR-250816
P48454	Q6VAB6	1	dephosphorylation	up-regulates activity	0.259	These findings indicate that calcineurin modulates the phosphorylation state of KSR2, but not KSR1, and identifies S198, T287, and the S310 14-3-3 binding site as the KSR2 residues targeted by calcineurin.\|the negative regulators 14-3-3	SIGNOR-248527
Q15833	Q00535	0	phosphorylation	down-regulates	0.2	It was shown that munc18 inhibition of neuronal syntaxin 1 can be overcome by cdk5 phosphorylation, indicating that structural change disrupts the syntaxin-munc18 interaction.	SIGNOR-157528
P68431	Q9UKI8	0	phosphorylation	up-regulates activity	0.2	Purified tlk1b phosphorylated histone h3 at s(10) with high specificity both in a mix of core histones and in isolated chromatin, suggesting that histone h3 is a physiological substrate for tlk1b. Phosphorylation of H3 has been linked to the activation of the immediate-early genes upon mitogenic stimulation, and to chromatin condensation during mitotic/meiotic events.	SIGNOR-107037
O14818	P42684	0	phosphorylation	down-regulates	0.607	Proteasome-mediated proteolysis is a primary protein degradation pathway in cells. The present study demonstrates that c-abl and arg (abl-related gene) tyrosine kinases associate with and phosphorylate the proteasome psma7 (alpha4) subunit at tyr-153. Consequently, proteasome-dependent proteolysis is compromised	SIGNOR-146589
P01106	Q9Y4K3	0	ubiquitination	down-regulates activity	0.344	We posited that TRAF6 ubiquitination of MYC at K148 prevents its acetylation, which results in diminished MYC activity ( xref ).	SIGNOR-278563
P43250	P14416	1	phosphorylation	down-regulates activity	0.447	GRK6 is located predominantly in dopaminergic neurons [ xref ] and functionally phosphorylates DRD2.	SIGNOR-279046
Q02156	Q86XR7	1	phosphorylation	up-regulates	0.573	Here we show that tram is transiently phosphorylated by pkcepsilon on serine-16 our study provides a possible target for these molecules in lps signaling. Dag may activate pkc?, Leading to the phosphorylation and activation of tram.	SIGNOR-146991
P03186	Q9Y4K3	1	deubiquitination	down-regulates activity	0.2	EBV-encoded BPLF1 interacts with and deubiquitinates TRAF6 to inhibit NF-κB signaling during lytic infection. Once lytic replication is induced, BPLF1 then deubiquitinates and inactivates TRAF6 to further block NF-κB signaling, promoting efficient viral genome replication.	SIGNOR-266739
P05107	P12931	0	phosphorylation	down-regulates activity	0.449	PTKs of the JAK and SRC families have a regulatory role in LFA-1 affinity triggering, with JAKs showing a positive role (3), whereas SRCs possibly have a negative role.	SIGNOR-254740
Q96S53	P23528	1	phosphorylation	down-regulates activity	0.503	Like tesk1, tesk2 phosphorylated cofilin specifically at ser-3 and induced formation of actin stress fibers and focal adhesions.	SIGNOR-108753
O15085	P61586	1	guanine nucleotide exchange factor	up-regulates activity	0.903	We therefore developed a screening-compatible live-cell imaging assay, using FRET-based biosensors for the prototype GTPases RHOA, RAC1 and CDC4215,19,20 (Extended Data Fig. 2 and Supplementary Note 1)\|We found catalytic activities for 45/75 RhoGEFs and 48/63 RhoGAPs\| Our data thus not only reveal extensive promiscuity among regulators, but also that the inactivating RhoGAPs are less selective than the activating RhoGEFs (p-value=0.02)(Supplementary Table 2).	SIGNOR-260538
Q9NRF2	P11912	1	dephosphorylation	down-regulates activity	0.2	SHP-1 is recruited by the phosphorylated ITIM-bearing receptors such as CD22 and it dephosphorylates proximal BCR signaling molecules such as CD79, SYK, BLNK.	SIGNOR-268457
P23786	Q86TM6	0	ubiquitination	down-regulates quantity	0.2	Taken together, these data suggest that HRD1 selectively and specifically downregulates intracellular CPT2 levels.\|These results demonstrate that HRD1 ubiquitinates CPT2, which is processed through Lys-48-linked ubiquitin chains.	SIGNOR-278723
Q13507	Q13976	0	phosphorylation	down-regulates	0.408	The present study demonstrates that human trpc3 expressed in hek293 cells forms store-operated ca2+ influx channels, the activity of which is inhibited by pkg. The inhibition is due to a direct phosphorylation of pkg on trpc3 channels at position t11 and s263.	SIGNOR-142961
Q13829	P68400	0	phosphorylation	up-regulates	0.2	It was demonstrated that ck2 could phosphorylate tnfaip1 in vitro and in vivo, which facilitated the distribution of tnfaip1 in nucleus and enhanced its interaction with pcna. It is suggested that the phosphorylation of tnfaip1 may be required for its functions.	SIGNOR-188849
Q8IUC6	Q9NWF9	0	ubiquitination	down-regulates quantity by destabilization	0.355	Triad3A promotes proteolytic degradation of adapter proteins. A, Triad3A promotes down-regulation of TIRAP, TRIF, and RIP1 proteins.	SIGNOR-271609
P06493	Q9Y5T5	1	phosphorylation	up-regulates	0.455	Here, we report that cyclin-dependent kinase 1 (cdk1) phosphorylates the histone h2a deubiquitinase ubp-m at serine 552 (s552p), and, importantly, this phosphorylation is required for cell cycle progression.	SIGNOR-202678
P35398	Q16620	1	transcriptional regulation	up-regulates quantity by expression	0.266	Some genes which are directly regulated by RORA such as NLGN1 and NTRK2 have been shown to be associated with increased susceptibility to ASD (Correia et al. 2010; Ylisaukko-oja et al. 2005).	SIGNOR-265137
Q96J02	Q8NEA6	1	ubiquitination	down-regulates quantity	0.331	Itch promotes proteolytic degradation of Glis3.\|Since Itch interacts with and ubiquitinates Glis3, it was of interest to determine which regions were necessary for Itch directed degradation of Glis3.	SIGNOR-278653
P17542	Q5D1E8	0	post transcriptional regulation	up-regulates quantity	0.2	Here, we show that Regnase-1 regulates self-renewal of HSPCs through modulating the stability of Gata2 and Tal1 mRNA	SIGNOR-259944
Q9GZR7	Q00987	0	polyubiquitination	up-regulates activity	0.334	MDM2 mediates nonproteolytic polyubiquitylation of the DEAD-Box RNA helicase DDX24. Unexpectedly, however, the polyubiquitylation of DDX24 did not elicit its proteasomal degradation but rather promoted its association with preribosomal ribonucleoprotein (pre-rRNP) processing complexes that are required for the early steps of pre-rRNA processing.	SIGNOR-272845
P28324	Q16549	0	phosphorylation	up-regulates	0.2	In contrast, the tcf sap-1a is efficiently phosphorylated by p38 map kinase in vitro and in vivo on the homologous residues ser381 and ser387	SIGNOR-47771
P00519	Q9H2X6	1	phosphorylation	up-regulates activity	0.403	The Tyrosine Kinase c-Abl Promotes Homeodomain-interacting Protein Kinase 2 (HIPK2) Accumulation and Activation in Response to DNA Damage	SIGNOR-260936
P61586	Q7Z5H3	0	gtpase-activating protein	down-regulates activity	0.564	We therefore developed a screening-compatible live-cell imaging assay, using FRET-based biosensors for the prototype GTPases RHOA, RAC1 and CDC4215,19,20 (Extended Data Fig. 2 and Supplementary Note 1)\|We found catalytic activities for 45/75 RhoGEFs and 48/63 RhoGAPs\| Our data thus not only reveal extensive promiscuity among regulators, but also that the inactivating RhoGAPs are less selective than the activating RhoGEFs (p-value=0.02)(Supplementary Table 2).	SIGNOR-260476
Q96KB5	Q13547	1	phosphorylation	up-regulates activity	0.245	TOPK overexpression promotes HDAC1 and HDAC2 phosphorylation and Histone 3 and Histone 4 acetylation in BV2 cells.\|The results of in vitro studies further confirmed the effect of TOPK on HDAC activity by showing that TOPK overexpression significantly up-regulated p-HDAC1 and p-HDAC2, resulting in an increase in the acetylation of histones H3 and H4 in BV2 cells.	SIGNOR-279086
O15350	Q9H0M0	0	polyubiquitination	down-regulates quantity by destabilization	0.283	WWP1 in complex with WWP2 specifically regulates ΔNp73. In our study, we identified WWP2, an E3 ligase, as a novel p73-associated protein that ubiquitinates and degrades p73. In contrast, WWP2 heterodimerizes with another E3 ligase, WWP1, which specifically ubiquitinates and degrades ΔNp73.	SIGNOR-272232
Q6VVB1	O14641	1	polyubiquitination	down-regulates quantity by destabilization	0.462	We have also found that malin enhances K48- and K63-linked ubiquitination of dishevelled2 that could lead to its degradation through both proteasome and autophagy. Altogether, our results indicate that malin regulates Wnt signaling pathway through the degradation of dishevelled2 and suggest possible deregulation of Wnt signaling in Lafora disease.	SIGNOR-272005
P42658	Q9NZV8	1	relocalization	up-regulates activity	0.548	DPPX-S reduced energy barriers of the voltage-dependent transitions; therefore, this auxiliary subunit may exert a catalytic effect on voltage-dependent gating of Kv4.2 channels. DPPX-S may also accelerate coupled inactivation indirectly	SIGNOR-269005
P35558	Q53ET0	0	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
O60502	P08237	1	deglycosylation	up-regulates activity	0.2	Our previous investigation on O-GlcNAcylation of PFK1 has demonstrated that O-GlcNAcylation inhibits PFK1 enzyme activity\|In cells, a single set of antagonistic enzymes-O-GlcNAc transferase (OGT) and O-GlcNAc hydrolase are responsible for the addition and removal of GlcNAc moiety, respectively.	SIGNOR-267607
Q9UEW8	P13569	1	phosphorylation	down-regulates activity	0.345	SPAK phosphorylates the transporters to reduce their surface expression and thus their activity and consequently inhibits ductal secretion to stabilize the resting state. PP1 reverses the effect of SPAK. Molecular analysis revealed that the WNK kinases acted as scaffolds to recruit SPAK, which phosphorylated CFTR and NBCe1-B, reducing their cell surface expression.	SIGNOR-263134
P17612	P11309	1	phosphorylation	up-regulates activity	0.266	In this study, we found that PKCα stabilized and activated PIM-1L by phosphorylation at Ser65. The PIM-1L phosphorylation suppressed sotrastaurin-induced apoptosis. These findings suggest that PKCα promotes cell survival and proliferation by upregulating PIM-1L in acute myeloid leukemia.	SIGNOR-256153
Q9NQR1	O60729	0	dephosphorylation	down-regulates quantity by destabilization	0.2	The dephosphorylation of S29 during late mitosis by the Cdc14 phosphatases was required for APC(cdh1)-mediated ubiquitination of PR-Set7 and subsequent proteolysis.	SIGNOR-248339
Q13158	Q13233	0	phosphorylation	down-regulates activity	0.503	The results clearly show that fadd phosphorylation at ser194 affects functions both upstream and downstream of the mekk1/mkk7/jnk1 pathway and is closely associated with chemosensitivity in prostate cancer cells	SIGNOR-123168
P03372	Q9Y5X4	0	transcriptional regulation	up-regulates quantity by expression	0.251	NR2E3 directly regulates expression of ESR1 \| Furthermore, overexpression of exogenous NR2E3 further increased expression of ESR1 and its downstream targets as well as its transcriptional activity in MCF-7 cells (Fig S1 of Supporting Information), strongly demonstrating that NR2E3 regulates ESR1 expression and subsequent ESR1-mediated induction of target genes.	SIGNOR-266207
P08670	Q05513	0	phosphorylation	up-regulates activity	0.2	Results suggest that aPKCs target multiple activation sites (Ser33/39/56) on Vimentin and therefore is essential for VIF dynamics regulation during the metastasis of prostate cancer cells.	SIGNOR-277622
P35222	Q05655	0	phosphorylation	down-regulates activity	0.269	Moreover, protein kinase Cδ, which directly phosphorylates β-catenin at Ser715, is required for the TRIM33–β-catenin interaction. \| Phosphorylation of β-catenin Ser715 is critical for TRIM33-induced β-catenin degradation	SIGNOR-260897
P49840	P05771	0	phosphorylation	down-regulates	0.327	Convergence of multiple signaling cascades at glycogen synthase kinase 3: edg receptor-mediated phosphorylation and inactivation by lysophosphatidic acid through a protein kinase c-dependent intracellular pathway.	SIGNOR-115718
O75582	P35222	1	phosphorylation	up-regulates activity	0.2	Co-transfection of MSK1 increased beta-catenin transcriptional activity in a dose dependent manner (XREF_FIG).\|Our in vitro kinase assay showed that MSK1 can directly phosphorylate beta-catenin at Ser 552.	SIGNOR-278247
Q969R5	Q13315	0	phosphorylation	up-regulates activity	0.2	L3MBTL2 links RNF8 and RNF168 in the DNA double strand break response. The protein kinase ATM phosphorylates L3MBTL2, which recruits it to the DNA lesion by promoting the interaction between MDC1 and L3MBTL2. L3MBTL2 is subsequently ubiquitinated by RNF8, which acts as a docking site for RNF168, thereby recruiting the ubiquitin ligase to the damage site. RNF168, in turn, ubiquitinates H2A-type histones to amplify the DNA damage response and recruit downstream DNA repair proteins for proper DSB signaling.	SIGNOR-266785
Q99986	P05412	1	phosphorylation	up-regulates	0.512	Vrk1 phosphorylates c-jun in ser63 and ser73 in vitro...VRK1 Activates c-jun dependent transcription	SIGNOR-127073
Q7Z6Z7	P15172	1	ubiquitination	down-regulates quantity	0.343	Importantly, addition of WT HUWE1 to a proteolytic reaction mixture enhanced the degradation of MyoD.\|Mass-spectrometry analyses show that HUWE1 can ubiquitinate MyoD at its N-terminal residue, though the preferred sites are - at least in a cell free system - the internal lysines of the protein.	SIGNOR-278694
P17252	Q92934	1	phosphorylation	down-regulates activity	0.2	Phosphorylation of BAD at ser112 and ser136 in the setting of lapatinib treatment was fully restored by PRKACA expression in BT474, SKBr3, and ZR-75-30 cells (XREF_FIG).\|We found that neither PRKACA nor PIM1 restored MAPK or PI3K activation after lapatinib or trastuzumab treatment, but rather inactivated the pro apoptotic protein BAD, thereby permitting survival signaling through BCL-XL.	SIGNOR-280080
P54764	Q12857	0	transcriptional regulation	up-regulates quantity	0.2	For example, within the NFI targetome, we identified 6 collagen genes, 13 genes encoding potassium channel or glutamate receptor subunits and a range of factors related to axon guidance (e.g. Slit1, Robo1, Epha4, Epha5, Epha8)	SIGNOR-268894
Q96L92	Q16539	0	phosphorylation	down-regulates activity	0.2	Altogether, our study suggests that MAPK11 and MAPK14 mediate the phosphorylation of SNX27 at Ser51 in vitro and in vivo.	SIGNOR-279069
P26358	P24941	0	phosphorylation	up-regulates	0.342	We report that cyclin-dependent kinases (cdks) 1, 2 and 5 can phosphorylate ser154 of human dnmt1 in vitro. Further evidence of phosphorylation of endogenous dnmt1 at position 154 by cdks is also found in 293 cells treated with roscovitine, a specific inhibitor of cdk1, 2 and 5	SIGNOR-173681
P78357	Q13882	0	phosphorylation	up-regulates activity	0.2	As a consequence, Brk stimulates p190 and attenuates p120 functions, leading to RhoA inactivation and Ras activation, respectively.\|Brk phosphorylates p190 at the Y (1105) residue both in vitro and in vivo, thereby promoting the association of p190 with p120RasGAP (p120).	SIGNOR-279274
Q16539	Q9Y6Q9	1	phosphorylation	up-regulates activity	0.526	P38 MAPK and JNK can phosphorylate multiple sites on SRC-3, including S505, S543, S860, and S867. Our results suggest that several kinases are important for phosphorylating SRC-3 and enhancing its interaction with DNA-dependent transcription factors and other coactivators.	SIGNOR-250103
P27361	P15336	1	phosphorylation	up-regulates	0.739	Here, we show that in fibroblasts, insulin, epidermal growth factor (egf) and serum activate atf2 via a so far unknown two-step mechanism involving two distinct ras effector pathways: the raf-mek-erk pathway induces phosphorylation of atf2 thr71, whereas subsequent atf2 thr69 phosphorylation requires the ral-ralgds-src-p38 pathway.	SIGNOR-90533
Q00987	Q9GZR7	1	polyubiquitination	up-regulates activity	0.334	MDM2 mediates nonproteolytic polyubiquitylation of the DEAD-Box RNA helicase DDX24. Unexpectedly, however, the polyubiquitylation of DDX24 did not elicit its proteasomal degradation but rather promoted its association with preribosomal ribonucleoprotein (pre-rRNP) processing complexes that are required for the early steps of pre-rRNA processing.	SIGNOR-272845

P17612

P30305

1

phosphorylation

up-regulates activity

0.2

Overall, PRKACA may directly phosphorylate CDC25B on Ser321 to control cell cycle progression in mouse-fertilized eggs [ xref ].|PRKACA phosphorylates and activates CDC25B in fertilized eggs of mice [ xref ].

SIGNOR-280077

Q12981

Q96GF1

0

polyubiquitination

up-regulates activity

0.533

RNF185 functions as a ubiquitin E3 ligase, enabling BNIP1-p62 interaction. Here we show that human RNF185 is a mitochondrial ubiquitin E3 ligase that regulates selective mitochondrial autophagy in cultured cells. Human BNIP1 colocalizes with RNF185 at mitochondria and is polyubiquitinated by RNF185 through K63-based ubiquitin linkage in vivo. The polyubiquitinated BNIP1 is capable of recruiting autophagy receptor p62, which simultaneously binds both ubiquitin and LC3 to link ubiquitination and autophagy. RNF185 interacts with BNIP1 and ATG5

SIGNOR-271931

P63279

O75030

1

ubiquitination

down-regulates

0.565

Furthermore, we identified lysine 201 as a potential ubiquitination site. A lysine to arginine mutation abolished mitf (k201r) degradation by hubc9 in vivo.

SIGNOR-75117

Q99683

P31749

0

phosphorylation

down-regulates activity

0.729

Akt phosphorylates and negatively regulates apoptosis signal-regulating kinase 1 akt decreased ask1 kinase activity stimulated by both oxidative stress and overexpression in 293 cells by phosphorylating a consensus akt site at serine 83 of ask1.

SIGNOR-252465

P17252

P08567

1

phosphorylation

up-regulates

0.28

To determine the role of pkc-dependent phosphorylation in pleckstrin function, we mapped the phosphorylation sites in vivo of wild-type and site-directed mutants of pleckstrin expressed in cos cells. Phosphorylation was found to occur almost exclusively on ser-113 and ser-117. Replacing all these sites with glycine decreased phosphorylation by > 90% and reduced pleckstrin's ability to inhibit phosphoinositide hydrolysis by as much as 80%.

SIGNOR-40048

O75807

P18848

0

transcriptional regulation

up-regulates quantity by expression

0.657

ATF4 also induces another bZIP protein C/EBP-homologous protein (CHOP), which is responsible for triggering apoptosis in cells under prolonged ER stress. ATF4 and CHOP further induce growth arrest and DNA damage–inducible protein 34 (GADD34),a regulatory subunit of protein phosphatase 1 (PP1) that dephosphorylates eIF2α. This negative feedback mechanism enables protein synthesis to resume after resolution of ER stress.

SIGNOR-260172

P51955

Q13188

0

phosphorylation

up-regulates

0.244

Our data suggest that mst2 phosphorylates nek2a thereby recruiting nek2a to centrosomes and promoting phosphorylation and displacement of centrosomal linker proteins

SIGNOR-169539

P23769

O60216

0

relocalization

down-regulates activity

0.325

Large-scale AML genome re-sequencing efforts have identified novel recurrently mutated genes, including the members of the cohesin complex (RAD21, SMC3, SMC1A, and STAG2), implicated in the pathogenesis of this disease.Using ATAC-seq, we determined that mutant cohesin lead to a state of elevated chromatin accessibility and higher predicted binding at transcription factor binding sites for ERG, GATA2, and RUNX1. Moreover, using ChIP-Seq, we formally demonstrated increased binding of GATA2 and RUNX1 to these sites. Finally, we demonstrated that knockdown of these three TFs in human HSPC can revert the differentiation block induced by mutant cohesin. These results support a model in which mutant cohesin impairs hematopoietic differentiation and enforces stem cell programs through the modulation of ERG, GATA2, and RUNX1 chromatin accessibility, expression, and activity.

SIGNOR-261513

P63000

Q17R89

0

gtpase-activating protein

down-regulates activity

0.589

We therefore developed a screening-compatible live-cell imaging assay, using FRET-based biosensors for the prototype GTPases RHOA, RAC1 and CDC4215,19,20 (Extended Data Fig. 2 and Supplementary Note 1)|We found catalytic activities for 45/75 RhoGEFs and 48/63 RhoGAPs| Our data thus not only reveal extensive promiscuity among regulators, but also that the inactivating RhoGAPs are less selective than the activating RhoGEFs (p-value=0.02)(Supplementary Table 2).

SIGNOR-260498

O14920

Q04206

1

phosphorylation

up-regulates activity

0.886

Rela is phosphorylated at ser536 by ikkbeta, ikkalfa, ikkepsilon, nf-kb activating kinase (nak, also known as tank-binding kinase-1 tbk1) and rsk1 (also known as p90 ribosomal protein s6 kinase (p90s6k). We now present evidence that suggests that the upstream kinase ikkbeta plays an important role in tax-induced p53 inhibition through phosphorylation of p65/rela at ser-536. Ikkbeta plays an important role in tax-induced p53 inhibition through phosphorylation of p65/rela at ser-536.

SIGNOR-138903

P17612

Q05469

1

phosphorylation

up-regulates activity

0.602

HSL activity is known to be regulated by phosphorylation (3). PKA increases HSL activity via phosphorylation at Ser563, Ser659, and Ser660 (14,15), although phosphorylation at Ser565 by glycogen synthase kinase, AMP-dependent protein kinase, or Ca2+/calmodulin-dependent protein kinase II has been reported to prevent activation of the enzyme

SIGNOR-249202

Q05655

P17096

1

phosphorylation

down-regulates

0.263

In this study, we showed that the pkc-mediated phosphorylation of hmg-i exerted a very potent inhibition on the binding of this protein to the at-rich promoter regions of both pkc g and ng genes. The purified hmg-i can be phosphorylated by pkc a,b, g, and d but is poorly phosphorylated by pkc e and z. We have mapped two major sites of phosphorylation by pkc at ser44 and ser64

SIGNOR-73610

Q96PH1

P00519

0

phosphorylation

up-regulates activity

0.303

As shown in Fig. xref and c, c-Abl-phosphorylated NOX5 was mostly inhibited when c-Abl plasmid co-transfected with NOX5 Y476/Y478F mutant, then the NOX5 Y487F mutant, but not with NOX5 Y519F mutant.|Collectively, these results indicate that Pyk2 may act as a scaffolding protein for c-Abl stimulation of NOX5 activity in Pyk2 and NOX5 complex, and c-Abl-enhanced NOX5 activity is mainly dependent on phosphorylation of NOX5 Tyr 476/478 sites.

SIGNOR-280170

P33981

P10636

1

phosphorylation

up-regulates activity

0.2

Fig. 6C-1 shows that the GST-TTK fusion protein phosphorylated both tau and tubulin, but the phosphorylating activity on tau was much higher than that on tubulin.

SIGNOR-279132

P49356

P01116

1

null

up-regulates activity

0.419

Major investments have been made to target Ras through indirect routes. Inhibition of farnesyl transferase to block Ras maturation has failed in large clinical trials.

SIGNOR-242556

Q8TBB1

O95477

1

ubiquitination

down-regulates quantity by destabilization

0.242

We used the Ligand of Numb protein X (LNX) family of E3s, a group of PDZ domain-containing RING-type E3 ubiquitin ligases, to demonstrate the feasibility of this strategy. Many potential substrates of LNX E3s were identified. Eight of the nine selected candidates were ubiquitinated in vitro, and two novel endogenous substrates, PDZ-binding kinase (PBK) and breakpoint cluster region protein (BCR), were confirmed in vivo.

SIGNOR-272902

P07711

P59594

1

cleavage

up-regulates activity

0.2

A cell-free membrane-fusion system demonstrates that engagement of receptor followed by proteolysis is required for SARS-CoV membrane fusion and indicates that cathepsin L is sufficient to activate membrane fusion by SARS-CoV S. These results suggest that SARS-CoV infection results from a unique, three-step process: receptor binding and induced conformational changes in S glycoprotein followed by cathepsin L proteolysis within endosomes. The requirement for cathepsin L proteolysis identifies a previously uncharacterized class of inhibitor for SARS-CoV infection.

SIGNOR-260218

Q9H9Q4

P31749

0

phosphorylation

down-regulates quantity by destabilization

0.358

Akt1 phosphorylates XLF at T181 Here, we report that Akt phosphorylates XLF at Thr181 to trigger its dissociation from the DNA ligase IV/XRCC4 complex, and promotes its interaction with 14-3-3β leading to XLF cytoplasmic retention, where cytosolic XLF is subsequently degraded by SCF(β-TRCP) in a CKI-dependent manner.

SIGNOR-276881

Q16539

P45985

0

phosphorylation

up-regulates activity

0.591

Two human MAP kinase kinases (MKK3 and MKK4) were cloned that phosphorylate and activate p38 MAP kinase.

SIGNOR-34121

Q16539

Q13541

1

phosphorylation

down-regulates activity

0.433

4E-BP1 Is Phosphorylated in Vitro by Active p38 Kinase. In the present study we demonstrated that UVB induced 4E-BP1 phosphorylation at multiple sites, Thr-36, Thr-45, Ser-64, and Thr-69, leading to dissociation of 4E-BP1 from eIF-4E.

SIGNOR-250097

Q00535

Q16555

1

phosphorylation

down-regulates activity

0.655

Cdk5 and DYRK2 phosphorylate CRMP2 and CRMP4, respectively, priming these proteins at S522 before their subsequent phosphorylation by GSK-3b at T509, T516 and S518|e CRMP2 phosphorylation by GSK-3b disrupts its interaction with tubulin (Yamashita & Goshima, 2012), leading to growth inhibition

SIGNOR-264838

Q9HCE7

P31749

0

phosphorylation

up-regulates activity

0.352

Furthermore, phosphorylation of Smurf1 by Akt1 was carried out specifically on the T145 residue, as mutation of this site abolished recognition of Smurf1 by the Akt1 phosphorylation motif antibody (Figure 5D).|We also identified that Smurf1 itself is targeted for phosphorylation by Akt1 and Akt2, regulating its stability.

SIGNOR-279778

Q15910

P24941

0

phosphorylation

up-regulates activity

0.547

Here, we demonstrate that the phosphorylation of EZH2 by cyclin-dependent kinases at Thr416 creates a docking site for the ForkHead-associated domain of NIPP1.

SIGNOR-255656

P54646

P17612

0

phosphorylation

down-regulates

0.42

Pka associates with and phosphorylates ampk?1 At ser-173 to impede threonine thr-172 phosphorylation and thus activation of ampk1 by lkb1 in response to lipolytic signals

SIGNOR-161860

P14598

P31749

0

phosphorylation

up-regulates

0.559

Akt phosphorylates p47phox and mediates respiratory burst activity in human neutrophils. A direct interaction between p47(phox) and akt was shown. Active recombinant akt phosphorylated recombinant p47(phox) in vitro. Mutation analysis indicated that 2 aa residues, ser(304) and ser(328), were phosphorylated by akt. Inhibition of akt activity also inhibited fmlp-stimulated neutrophil chemotaxis.

SIGNOR-252586

P49841

Q00613

1

phosphorylation

down-regulates activity

0.557

Ser-303 is phosphorylated by glycogen synthase kinase 3 (GSK3) through a mechanism dependent on primary phosphorylation of Ser-307 by MAPK. Secondary phosphorylation of Ser-303 by GSK3 may thus repress the activity of HSF-1, and its requirement for priming by MAPK phosphorylation of Ser-307 provides a potential link between the MAPK cascade and HSF-1.

SIGNOR-251216

Q8WXD9

P54762

0

phosphorylation

up-regulates activity

0.283

EphB1 phosphorylates Caskin1 on tyrosine 296 and 336. Tyrosine phosphorylated Caskin1 then likely promotes reorganization of the actin cytoskeleton leading to spine formation.

SIGNOR-262861

P37231

P00519

0

phosphorylation

up-regulates quantity

0.341

We show that the tyrosine kinase Abelson murine leukemia viral oncogene (cAbl) is an adipogenic key regulator. c-Abl promotes adipogenesis by phosphorylation and subsequent stabilization of PPARγ.

SIGNOR-262297

P17252

P13498

1

phosphorylation

up-regulates

0.2

Phosphorylation of p22phox on threonine 147 enhances NADPH oxidase activity by promoting p47phox binding. | Threonine 147 of p22phox Is Phosphorylated by PKC-α and PKC-δ in Vitro

SIGNOR-260891

Q9UPU5

Q13315

0

phosphorylation

up-regulates activity

0.25

Taken together, these data suggest that the ATM kinase mediated phosphorylation of USP24 is involved in USP24 stabilization/up regulation following UV irradiation.|Taken together, these data suggest that the ATM kinase-mediated phosphorylation of USP24 is involved in USP24 stabilization/up-regulation following UV irradiation.

SIGNOR-280043

P23470

P08581

1

dephosphorylation

down-regulates activity

0.317

PTPRG activation by the P1-WD peptide affected the tyrosine phosphorylation of several signaling molecules. Data analysis identified 31 molecules whose phosphorylation was modified in a statistically significant manner (Table I). inhibition of ABL1, BMX, BTK, DAB1, ITGB1, JAK2, KDR, KIT, LIMK1, MET, PDGFRB, SHC1, and VCL correlates with tyrosine dephosphorylation. In contrast, SRC inhibition correlates with hyperphosphorylation of the inhibitory Tyr530 residue and with dephosphorylation of the activatory Tyr419. Moreover, CDK2 and CTTN inhibition correlates with a hyperphosphorylation of the inhibitory Tyr15 and Tyr470, respectively. In contrast, a subgroup of 13 proteins, including BLNK, DOK2, ERBB2, GRIN2B, INSR, PDGFRA, PRKCD, PXN, STAT1, STAT2, STAT3, STAT5A, and ZAP70, appears to be activated by PTPRG activity.

SIGNOR-254712

P15336

P45984

0

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

Q14676

Q13315

0

phosphorylation

up-regulates

0.846

We show that, in response to ionizing radiation, mdc1 is hyperphosphorylated in an atm-dependent manner, and rapidly relocalizes to nuclear foci that also contain the mre11 complex, phosphorylated histone h2ax and 53bp1.

SIGNOR-98798

P20393

O00327

1

transcriptional regulation

down-regulates quantity by repression

0.671

In this study, we found that NPAS2, like BMAL1, is a direct target gene of RORα and REV-ERBα. it appears in the context of the NPAS2 promoter RORα functions as a transcriptional activator, but REV-ERBα may only function as an inhibitor of RORα activity by blocking binding.

SIGNOR-267983

P17676

P37231

1

transcriptional regulation

up-regulates quantity

0.729

Induction of C/EBP beta DNA-binding activity in NIH-3T3 beta 2 cells exposed to dexamethasone in the presence of insulin and fetal bovine serum activates the expression of an adipocyte-specific nuclear hormone receptor, PPAR gamma, that stimulates the conversion of these fibroblasts into committed preadipocytes

SIGNOR-255730

Q16539

P10415

1

phosphorylation

down-regulates activity

0.334

Bcl-2 phosphorylation by p38 mapkin this study, we identify, by using mass spectrometry techniques and specific anti-phosphopeptide antibodies, ser(87) and thr(56) as the bcl-2 residues phosphorylated by p38 mapk and show that phosphorylation of these residues is always associated with a decrease in the antiapoptotic potential of bcl-2 protein.

SIGNOR-146786

O43684

O43683

0

relocalization

up-regulates activity

0.943

Spindle checkpoint protein Bub1 is required for kinetochore localization of Mad1, Mad2, Bub3, and CENP-E, independently of its kinase activity

SIGNOR-252019

P08581

Q14289

1

phosphorylation

up-regulates activity

0.28

In this study, using a protein array approach, we found that c-Met phosphorylates FAK and Pyk2 in medulloblastoma cells.|Our study shows for the first time that c-Met activates FAK and Pyk2 and that FAK and Pyk2 mediate the effects of c-Met in medulloblastoma.

SIGNOR-280040

P47712

Q9BUB5

0

phosphorylation

up-regulates activity

0.577

The results suggest that MNK1 or a closely related kinase is responsible for in vivo phosphorylation of cPLA2 on Ser-727.

SIGNOR-226633

P68400

Q96FW1

1

phosphorylation

up-regulates activity

0.319

Casein kinase 2 (CK2)-dependent phosphorylation of OTUB1 at Ser16 played a critical role in ODN- and cathepsin K siRNA-mediated p53 stabilization. |Furthermore, although OTUB1 dramatically induced p53 deubiquitination, its mutant (S16A) and deletion mutant did not have this effec

SIGNOR-276527

Q15418

P17676

1

phosphorylation

up-regulates activity

0.683

13 The data presented support previous findings that C/EBPbeta can be a molecular target of RSK1, 16 but provide the first indication that RSK1 can phosphorylate and activate C/EBPbeta to mediate the IL-6 signalling events in cholangiocarcinoma.|As mentioned above, RSK1 has been shown to activate C/EBPbeta in hepatic stellate cells in an experimental model of liver fibrosis.

SIGNOR-280112

P46527

O15297

0

dephosphorylation

down-regulates activity

0.259

Increased expression of wildtype WIP1 reduces stability of p27 Kip1 while increased expression of similar amounts of phosphatase-dead WIP1 has no effect on p27 Kip1 protein stability.|We demonstrate that wildtype, but not phosphatase-dead WIP1, efficiently dephosphorylates p27 Kip1 Ser140 both in vitro and in cells and that this dephosphorylation is sensitive to the WIP1 specific inhibitor GSK 2830371.

SIGNOR-277109

P68400

Q9UJY5

1

phosphorylation

down-regulates activity

0.504

Serine-355 of GGA1 is phosphorylated in vivo and in vitro. This inhibition is caused by the binding of an AC-LL sequence present in the hinge segment to the ligand-binding site in the VHS domain. The inhibition depends on the phosphorylation of a serine located three residues upstream of the AC-LL motif. The serine is phosphorylated by casein kinase 2 in in vitro assays.

SIGNOR-273623

P25963

Q9UQB9

0

phosphorylation

up-regulates activity

0.2

AURKC directly induces IkappaBalpha activation via an interaction between the two proteins, leading to phosphorylation of IkappaBalpha.|AURKC phosphorylates IkappaBalpha on S32 and binds its ankyrin repeat domain.

SIGNOR-278470

Q9Y6Q9

P49840

0

phosphorylation

down-regulates quantity by destabilization

0.2

GSK3 Phosphorylates SRC-3 on S505.In this report, we identified GSK3 as a kinase that phosphorylates SRC-3 on S505 and demonstrated that this phosphorylation modulates SRC-3 transcriptional function and turnover.

SIGNOR-276067

Q99075

P03956

0

cleavage

up-regulates activity

0.33

We have recently reported that HB-EGF is a substrate of MT1-MMP and that removal of the N-terminal fragment of HB-EGFby MT1-MMP converts the former into a hyperactive growthfactor that does not require heparin as a co-factor.

SIGNOR-278096

P43405

P40763

1

phosphorylation

up-regulates activity

0.552

The current study indicates that the plasma cell malignancy is also associated with Syk-activated STAT3 directly downstream of reelin-induced integrin \u03b21 engagement and FAK/Src activation (Figure xref ).|The integrin-activated spleen tyrosine kinase (Syk) was shown to promote STAT3 phosphorylation [42, 44].

SIGNOR-279298

Q13627

Q13247

1

phosphorylation

up-regulates activity

0.432

These results suggest that Dyrk1A enhances SRp55 promoted cTnT exon 5 inclusion.|These results supported the finding that phosphorylation of SRp55 by Dyrk1A promotes cTnT exon 5 inclusion.Alternative splicing of cTnT exon 5 is regulated developmentally.

SIGNOR-279166

P51608

Q13451

1

transcriptional regulation

down-regulates quantity by repression

0.306

These results are compatible with the hypothesis that MeCP2 associates with the Sgk and Fkbp5 promoters and has a repressive effect that is over-ridden by elevated glucocorticoids in response to stress.

SIGNOR-264542

P56645

P49674

0

phosphorylation

down-regulates activity

0.74

The CKI phosphorylation of mPer1 and mPer3 proteins results in their rapid degradation, which is dependent on the ubiquitin-proteasome pathway. Moreover, CKIepsilon and CKIdelta are able to induce nuclear translocation of mPer3, which requires its nuclear localization signal. The mutation in potential phosphorylation sites on mPer3 decreased the extent of both nuclear translocation and degradation of mPer3 that are stimulated by CKIepsilon. | In mut7 in which all of the conserved serine and threonine residues in this region were mutated, the ratio of the shifted band was greatly reduced reproducibly.

SIGNOR-250816

P48454

Q6VAB6

1

dephosphorylation

up-regulates activity

0.259

These findings indicate that calcineurin modulates the phosphorylation state of KSR2, but not KSR1, and identifies S198, T287, and the S310 14-3-3 binding site as the KSR2 residues targeted by calcineurin.|the negative regulators 14-3-3

SIGNOR-248527

Q15833

Q00535

0

phosphorylation

down-regulates

0.2

It was shown that munc18 inhibition of neuronal syntaxin 1 can be overcome by cdk5 phosphorylation, indicating that structural change disrupts the syntaxin-munc18 interaction.

SIGNOR-157528

P68431

Q9UKI8

0

phosphorylation

up-regulates activity

0.2

Purified tlk1b phosphorylated histone h3 at s(10) with high specificity both in a mix of core histones and in isolated chromatin, suggesting that histone h3 is a physiological substrate for tlk1b. Phosphorylation of H3 has been linked to the activation of the immediate-early genes upon mitogenic stimulation, and to chromatin condensation during mitotic/meiotic events.

SIGNOR-107037

O14818

P42684

0

phosphorylation

down-regulates

0.607

Proteasome-mediated proteolysis is a primary protein degradation pathway in cells. The present study demonstrates that c-abl and arg (abl-related gene) tyrosine kinases associate with and phosphorylate the proteasome psma7 (alpha4) subunit at tyr-153. Consequently, proteasome-dependent proteolysis is compromised

SIGNOR-146589

P01106

Q9Y4K3

0

ubiquitination

down-regulates activity

0.344

We posited that TRAF6 ubiquitination of MYC at K148 prevents its acetylation, which results in diminished MYC activity ( xref ).

SIGNOR-278563

P43250

P14416

1

phosphorylation

down-regulates activity

0.447

GRK6 is located predominantly in dopaminergic neurons [ xref ] and functionally phosphorylates DRD2.

SIGNOR-279046

Q02156

Q86XR7

1

phosphorylation

up-regulates

0.573

Here we show that tram is transiently phosphorylated by pkcepsilon on serine-16 our study provides a possible target for these molecules in lps signaling. Dag may activate pkc?, Leading to the phosphorylation and activation of tram.

SIGNOR-146991

P03186

Q9Y4K3

1

deubiquitination

down-regulates activity

0.2

EBV-encoded BPLF1 interacts with and deubiquitinates TRAF6 to inhibit NF-κB signaling during lytic infection. Once lytic replication is induced, BPLF1 then deubiquitinates and inactivates TRAF6 to further block NF-κB signaling, promoting efficient viral genome replication.

SIGNOR-266739

P05107

P12931

0

phosphorylation

down-regulates activity

0.449

PTKs of the JAK and SRC families have a regulatory role in LFA-1 affinity triggering, with JAKs showing a positive role (3), whereas SRCs possibly have a negative role.

SIGNOR-254740

Q96S53

P23528

1

phosphorylation

down-regulates activity

0.503

Like tesk1, tesk2 phosphorylated cofilin specifically at ser-3 and induced formation of actin stress fibers and focal adhesions.

SIGNOR-108753

O15085

P61586

1

guanine nucleotide exchange factor

up-regulates activity

0.903

We therefore developed a screening-compatible live-cell imaging assay, using FRET-based biosensors for the prototype GTPases RHOA, RAC1 and CDC4215,19,20 (Extended Data Fig. 2 and Supplementary Note 1)|We found catalytic activities for 45/75 RhoGEFs and 48/63 RhoGAPs| Our data thus not only reveal extensive promiscuity among regulators, but also that the inactivating RhoGAPs are less selective than the activating RhoGEFs (p-value=0.02)(Supplementary Table 2).

SIGNOR-260538

Q9NRF2

P11912

1

dephosphorylation

down-regulates activity

0.2

SHP-1 is recruited by the phosphorylated ITIM-bearing receptors such as CD22 and it dephosphorylates proximal BCR signaling molecules such as CD79, SYK, BLNK.

SIGNOR-268457

P23786

Q86TM6

0

ubiquitination

down-regulates quantity

0.2

Taken together, these data suggest that HRD1 selectively and specifically downregulates intracellular CPT2 levels.|These results demonstrate that HRD1 ubiquitinates CPT2, which is processed through Lys-48-linked ubiquitin chains.

SIGNOR-278723

Q13507

Q13976

0

phosphorylation

down-regulates

0.408

The present study demonstrates that human trpc3 expressed in hek293 cells forms store-operated ca2+ influx channels, the activity of which is inhibited by pkg. The inhibition is due to a direct phosphorylation of pkg on trpc3 channels at position t11 and s263.

SIGNOR-142961

Q13829

P68400

0

phosphorylation

up-regulates

0.2

It was demonstrated that ck2 could phosphorylate tnfaip1 in vitro and in vivo, which facilitated the distribution of tnfaip1 in nucleus and enhanced its interaction with pcna. It is suggested that the phosphorylation of tnfaip1 may be required for its functions.

SIGNOR-188849

Q8IUC6

Q9NWF9

0

ubiquitination

down-regulates quantity by destabilization

0.355

Triad3A promotes proteolytic degradation of adapter proteins. A, Triad3A promotes down-regulation of TIRAP, TRIF, and RIP1 proteins.

SIGNOR-271609

P06493

Q9Y5T5

1

phosphorylation

up-regulates

0.455

Here, we report that cyclin-dependent kinase 1 (cdk1) phosphorylates the histone h2a deubiquitinase ubp-m at serine 552 (s552p), and, importantly, this phosphorylation is required for cell cycle progression.

SIGNOR-202678

P35398

Q16620

1

transcriptional regulation

up-regulates quantity by expression

0.266

Some genes which are directly regulated by RORA such as NLGN1 and NTRK2 have been shown to be associated with increased susceptibility to ASD (Correia et al. 2010; Ylisaukko-oja et al. 2005).

SIGNOR-265137

Q96J02

Q8NEA6

1

ubiquitination

down-regulates quantity

0.331

Itch promotes proteolytic degradation of Glis3.|Since Itch interacts with and ubiquitinates Glis3, it was of interest to determine which regions were necessary for Itch directed degradation of Glis3.

SIGNOR-278653

P17542

Q5D1E8

0

post transcriptional regulation

up-regulates quantity

0.2

Here, we show that Regnase-1 regulates self-renewal of HSPCs through modulating the stability of Gata2 and Tal1 mRNA

SIGNOR-259944

Q9GZR7

Q00987

0

polyubiquitination

up-regulates activity

0.334

MDM2 mediates nonproteolytic polyubiquitylation of the DEAD-Box RNA helicase DDX24. Unexpectedly, however, the polyubiquitylation of DDX24 did not elicit its proteasomal degradation but rather promoted its association with preribosomal ribonucleoprotein (pre-rRNP) processing complexes that are required for the early steps of pre-rRNA processing.

SIGNOR-272845

P28324

Q16549

0

phosphorylation

up-regulates

0.2

In contrast, the tcf sap-1a is efficiently phosphorylated by p38 map kinase in vitro and in vivo on the homologous residues ser381 and ser387

SIGNOR-47771

P00519

Q9H2X6

1

phosphorylation

up-regulates activity

0.403

The Tyrosine Kinase c-Abl Promotes Homeodomain-interacting Protein Kinase 2 (HIPK2) Accumulation and Activation in Response to DNA Damage

SIGNOR-260936

P61586

Q7Z5H3

0

gtpase-activating protein

down-regulates activity

0.564

We therefore developed a screening-compatible live-cell imaging assay, using FRET-based biosensors for the prototype GTPases RHOA, RAC1 and CDC4215,19,20 (Extended Data Fig. 2 and Supplementary Note 1)|We found catalytic activities for 45/75 RhoGEFs and 48/63 RhoGAPs| Our data thus not only reveal extensive promiscuity among regulators, but also that the inactivating RhoGAPs are less selective than the activating RhoGEFs (p-value=0.02)(Supplementary Table 2).

SIGNOR-260476

Q96KB5

Q13547

1

phosphorylation

up-regulates activity

0.245

TOPK overexpression promotes HDAC1 and HDAC2 phosphorylation and Histone 3 and Histone 4 acetylation in BV2 cells.|The results of in vitro studies further confirmed the effect of TOPK on HDAC activity by showing that TOPK overexpression significantly up-regulated p-HDAC1 and p-HDAC2, resulting in an increase in the acetylation of histones H3 and H4 in BV2 cells.

SIGNOR-279086

O15350

Q9H0M0

0

polyubiquitination

down-regulates quantity by destabilization

0.283

WWP1 in complex with WWP2 specifically regulates ΔNp73. In our study, we identified WWP2, an E3 ligase, as a novel p73-associated protein that ubiquitinates and degrades p73. In contrast, WWP2 heterodimerizes with another E3 ligase, WWP1, which specifically ubiquitinates and degrades ΔNp73.

SIGNOR-272232

Q6VVB1

O14641

1

polyubiquitination

down-regulates quantity by destabilization

0.462

We have also found that malin enhances K48- and K63-linked ubiquitination of dishevelled2 that could lead to its degradation through both proteasome and autophagy. Altogether, our results indicate that malin regulates Wnt signaling pathway through the degradation of dishevelled2 and suggest possible deregulation of Wnt signaling in Lafora disease.

SIGNOR-272005

P42658

Q9NZV8

1

relocalization

up-regulates activity

0.548

DPPX-S reduced energy barriers of the voltage-dependent transitions; therefore, this auxiliary subunit may exert a catalytic effect on voltage-dependent gating of Kv4.2 channels. DPPX-S may also accelerate coupled inactivation indirectly

SIGNOR-269005

P35558

Q53ET0

0

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

O60502

P08237

1

deglycosylation

up-regulates activity

0.2

Our previous investigation on O-GlcNAcylation of PFK1 has demonstrated that O-GlcNAcylation inhibits PFK1 enzyme activity|In cells, a single set of antagonistic enzymes-O-GlcNAc transferase (OGT) and O-GlcNAc hydrolase are responsible for the addition and removal of GlcNAc moiety, respectively.

SIGNOR-267607

Q9UEW8

P13569

1

phosphorylation

down-regulates activity

0.345

SPAK phosphorylates the transporters to reduce their surface expression and thus their activity and consequently inhibits ductal secretion to stabilize the resting state. PP1 reverses the effect of SPAK. Molecular analysis revealed that the WNK kinases acted as scaffolds to recruit SPAK, which phosphorylated CFTR and NBCe1-B, reducing their cell surface expression.

SIGNOR-263134

P17612

P11309

1

phosphorylation

up-regulates activity

0.266

In this study, we found that PKCα stabilized and activated PIM-1L by phosphorylation at Ser65. The PIM-1L phosphorylation suppressed sotrastaurin-induced apoptosis. These findings suggest that PKCα promotes cell survival and proliferation by upregulating PIM-1L in acute myeloid leukemia.

SIGNOR-256153

Q9NQR1

O60729

0

dephosphorylation

down-regulates quantity by destabilization

0.2

The dephosphorylation of S29 during late mitosis by the Cdc14 phosphatases was required for APC(cdh1)-mediated ubiquitination of PR-Set7 and subsequent proteolysis.

SIGNOR-248339

Q13158

Q13233

0

phosphorylation

down-regulates activity

0.503

The results clearly show that fadd phosphorylation at ser194 affects functions both upstream and downstream of the mekk1/mkk7/jnk1 pathway and is closely associated with chemosensitivity in prostate cancer cells

SIGNOR-123168

P03372

Q9Y5X4

0

transcriptional regulation

up-regulates quantity by expression

0.251

NR2E3 directly regulates expression of ESR1 | Furthermore, overexpression of exogenous NR2E3 further increased expression of ESR1 and its downstream targets as well as its transcriptional activity in MCF-7 cells (Fig S1 of Supporting Information), strongly demonstrating that NR2E3 regulates ESR1 expression and subsequent ESR1-mediated induction of target genes.

SIGNOR-266207

P08670

Q05513

0

phosphorylation

up-regulates activity

0.2

Results suggest that aPKCs target multiple activation sites (Ser33/39/56) on Vimentin and therefore is essential for VIF dynamics regulation during the metastasis of prostate cancer cells.

SIGNOR-277622

P35222

Q05655

0

phosphorylation

down-regulates activity

0.269

Moreover, protein kinase Cδ, which directly phosphorylates β-catenin at Ser715, is required for the TRIM33–β-catenin interaction. | Phosphorylation of β-catenin Ser715 is critical for TRIM33-induced β-catenin degradation

SIGNOR-260897

P49840

P05771

0

phosphorylation

down-regulates

0.327

Convergence of multiple signaling cascades at glycogen synthase kinase 3: edg receptor-mediated phosphorylation and inactivation by lysophosphatidic acid through a protein kinase c-dependent intracellular pathway.

SIGNOR-115718

O75582

P35222

1

phosphorylation

up-regulates activity

0.2

Co-transfection of MSK1 increased beta-catenin transcriptional activity in a dose dependent manner (XREF_FIG).|Our in vitro kinase assay showed that MSK1 can directly phosphorylate beta-catenin at Ser 552.

SIGNOR-278247

Q969R5

Q13315

0

phosphorylation

up-regulates activity

0.2

L3MBTL2 links RNF8 and RNF168 in the DNA double strand break response. The protein kinase ATM phosphorylates L3MBTL2, which recruits it to the DNA lesion by promoting the interaction between MDC1 and L3MBTL2. L3MBTL2 is subsequently ubiquitinated by RNF8, which acts as a docking site for RNF168, thereby recruiting the ubiquitin ligase to the damage site. RNF168, in turn, ubiquitinates H2A-type histones to amplify the DNA damage response and recruit downstream DNA repair proteins for proper DSB signaling.

SIGNOR-266785

Q99986

P05412

1

phosphorylation

up-regulates

0.512

Vrk1 phosphorylates c-jun in ser63 and ser73 in vitro...VRK1 Activates c-jun dependent transcription

SIGNOR-127073

Q7Z6Z7

P15172

1

ubiquitination

down-regulates quantity

0.343

Importantly, addition of WT HUWE1 to a proteolytic reaction mixture enhanced the degradation of MyoD.|Mass-spectrometry analyses show that HUWE1 can ubiquitinate MyoD at its N-terminal residue, though the preferred sites are - at least in a cell free system - the internal lysines of the protein.

SIGNOR-278694

P17252

Q92934

1

phosphorylation

down-regulates activity

0.2

Phosphorylation of BAD at ser112 and ser136 in the setting of lapatinib treatment was fully restored by PRKACA expression in BT474, SKBr3, and ZR-75-30 cells (XREF_FIG).|We found that neither PRKACA nor PIM1 restored MAPK or PI3K activation after lapatinib or trastuzumab treatment, but rather inactivated the pro apoptotic protein BAD, thereby permitting survival signaling through BCL-XL.

SIGNOR-280080

P54764

Q12857

0

transcriptional regulation

up-regulates quantity

0.2

For example, within the NFI targetome, we identified 6 collagen genes, 13 genes encoding potassium channel or glutamate receptor subunits and a range of factors related to axon guidance (e.g. Slit1, Robo1, Epha4, Epha5, Epha8)

SIGNOR-268894

Q96L92

Q16539

0

phosphorylation

down-regulates activity

0.2

Altogether, our study suggests that MAPK11 and MAPK14 mediate the phosphorylation of SNX27 at Ser51 in vitro and in vivo.

SIGNOR-279069

P26358

P24941

0

phosphorylation

up-regulates

0.342

We report that cyclin-dependent kinases (cdks) 1, 2 and 5 can phosphorylate ser154 of human dnmt1 in vitro. Further evidence of phosphorylation of endogenous dnmt1 at position 154 by cdks is also found in 293 cells treated with roscovitine, a specific inhibitor of cdk1, 2 and 5

SIGNOR-173681

P78357

Q13882

0

phosphorylation

up-regulates activity

0.2

As a consequence, Brk stimulates p190 and attenuates p120 functions, leading to RhoA inactivation and Ras activation, respectively.|Brk phosphorylates p190 at the Y (1105) residue both in vitro and in vivo, thereby promoting the association of p190 with p120RasGAP (p120).

SIGNOR-279274

Q16539

Q9Y6Q9

1

phosphorylation

up-regulates activity

0.526

P38 MAPK and JNK can phosphorylate multiple sites on SRC-3, including S505, S543, S860, and S867. Our results suggest that several kinases are important for phosphorylating SRC-3 and enhancing its interaction with DNA-dependent transcription factors and other coactivators.

SIGNOR-250103

P27361

P15336

1

phosphorylation

up-regulates

0.739

Here, we show that in fibroblasts, insulin, epidermal growth factor (egf) and serum activate atf2 via a so far unknown two-step mechanism involving two distinct ras effector pathways: the raf-mek-erk pathway induces phosphorylation of atf2 thr71, whereas subsequent atf2 thr69 phosphorylation requires the ral-ralgds-src-p38 pathway.

SIGNOR-90533

Q00987

Q9GZR7

1

polyubiquitination

up-regulates activity

0.334

MDM2 mediates nonproteolytic polyubiquitylation of the DEAD-Box RNA helicase DDX24. Unexpectedly, however, the polyubiquitylation of DDX24 did not elicit its proteasomal degradation but rather promoted its association with preribosomal ribonucleoprotein (pre-rRNP) processing complexes that are required for the early steps of pre-rRNA processing.

SIGNOR-272845