GleghornLab/Signor_2class · Datasets at Hugging Face

IdA string	IdB string	labels int64	mechanism string	effect string	score float64	sentence string	signor_id string
Q9Y5X1	Q07912	0	phosphorylation	up-regulates	0.505	We have previously shown that sh3px1, phosphorylated by ack2 (activated cdc42-associated tyrosine kinase 2), regulates the degradation of egf (epidermal growth factor) receptor.	SIGNOR-142569
P62136	P06493	0	phosphorylation	down-regulates activity	0.575	Both of these pp1 isoforms contain an arg-pro-ile/val-thr-pro-pro-arg sequence near the c terminus, a known site of phosphorylation by cdc/cdk kinases, and phosphorylation attenuates phosphatase activity.	SIGNOR-151799
P10070	Q6PHR2	0	phosphorylation	up-regulates activity	0.621	We show that ULK3 is able to phosphorylate three mammalian GLI proteins in vitro	SIGNOR-260798
P49841	Q00653	1	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
P55212	P59595	1	cleavage	up-regulates activity	0.2	Caspase-6 is activated through the intrinsic pathway and mediates C-terminal cleavage of SARS-CoV N at residues 400 and 403	SIGNOR-260212
P17612	P48436	1	phosphorylation	up-regulates	0.465	We find that activation of camp-dependent protein kinase a (pka) induces phosphorylation of sox9 on its two s64 and s181 pka sites, and its nuclear localization by enhancing sox9 binding to the nucleocytoplasmic transport protein importin beta.	SIGNOR-137085
Q8IYT8	Q9Y478	1	phosphorylation	down-regulates	0.329	Ulk1/2 in turn phosphorylates all three subunits of ampk and thereby negatively regulates its activity	SIGNOR-173092
P06493	P22314	1	phosphorylation	up-regulates	0.405	Ubiquitin-activating enzyme, e1, is phosphorylated in mammalian cells by the protein kinase cdc2. Each serine residue was independently mutated to an alanine and analyzed by two-dimensional electrophoresis;only serine 4 was phosphorylated. Disruption of the basic amino acids within the nls resulted in loss of exclusive nuclear localization and a 90-95% decrease in the phosphorylation of ha1-e1	SIGNOR-31157
O95295	O43567	0	polyubiquitination	up-regulates activity	0.521	RNF13 directly interacted with snapin, a SNAP-25-interacting protein. Interestingly, snapin was ubiquitinated by RNF13 via the lysine-29 conjugated polyubiquitin chain, which in turn promoted the association of snapin with SNAP-25. Consistently, we found an attenuated interaction between snapin and SNAP-25 in the RNF13-null mice. Therefore, these results suggest that RNF13 is involved in the regulation of the SNARE complex, which thereby controls synaptic function.	SIGNOR-272044
P63104	Q05655	0	phosphorylation	down-regulates activity	0.446	We confirmed that MAPKAPK2 interacted with and phosphorylated 14-3-3zeta in vitro and in HEK293 cells. \| Experimentally, S58D mutation significantly impaired both 14-3-3zeta dimerization and binding to Raf-1.	SIGNOR-249222
Q14847	P05771	0	phosphorylation	down-regulates activity	0.2	Actin binding of human lim and sh3 protein is regulated by cgmp- and camp-dependent protein kinase phosphorylation on serine 146. Phosphorylation of lasp at ser-146 leads to a redistribution of the actin-bound protein from the tips of the cell membrane to the cytosol, accompanied with a reduced cell migration	SIGNOR-97942
P46937	Q9Y297	0	ubiquitination	down-regulates	0.544	This cascade of phosphorylation allows the binding of scfbetatrcp that promotes the ubiquitination and degradation of yap.	SIGNOR-201138
O95630	Q9HAU4	0	polyubiquitination	down-regulates quantity by destabilization	0.529	RNF11 recruits AMSH to Smurf2 E3 ligase. Smurf2 promotes ubiquitination of AMSH in the presence of wt RNF11. Previously, we have shown that RNF11 interacts with the HECT-type E3 ligases AIP4 and Smurf2. Here, we show that RNF11 binds to AMSH in mammalian cells and that this interaction is independent of the RNF11 RING-finger domain and the PY motif. Our results also demonstrate that AMSH is ubiquitinated by Smurf2 E3 ligase in the presence of RNF11 and that a consequent reduction in its steady-state level requires both RNF11 and Smurf2. RNF11 therefore recruits AMSH to Smurf2 for ubiquitination, leading to its degradation by the 26S proteasome.	SIGNOR-272951
O95140	Q9BXM7	0	phosphorylation	down-regulates quantity	0.81	If PINK1 is responsible for the degradation of Mfn2, then silencing PINK1 should induce mitochondrial fusion by upregulating Mfn2 expression.\|We show that downregulation of Mfn2 is induced by proteasomal degradation triggered by PINK1, which phosphorylates Mfn2 at S442.	SIGNOR-278208
Q93009	P62979	1	cleavage	up-regulates quantity	0.654	Here we provide data suggesting that two of the four mammalian ubiquitin precursors, UBA52 and UBA80, are processed mostly post-translationally whereas the other two, UBB and UBC, probably undergo a combination of co- and post-translational processing. Using an unbiased biochemical approach we found that UCHL3, USP9X, USP7, USP5 and Otulin/Gumby/FAM105b are by far the most active DUBs acting on these precursors.	SIGNOR-270824
P11831	Q05655	0	phosphorylation	down-regulates activity	0.2	Protein kinase C delta blocks immediate-early gene expression in senescent cells by inactivating serum response factor.\|The phosphorylation of T160 of SRF by PKC delta in vitro and in vivo led to loss of SRF DNA binding activity.	SIGNOR-279347
P40198	Q12913	0	dephosphorylation	down-regulates activity	0.387	We also determined that recombinant PTPRJ directly dephosphorylates the cytoplasmic tyrosine residues of purified full-length CEACAM3 and recognizes synthetic CEACAM3-derived phospho-peptides as substrates.\|We show depletion of PTPRJ results in a gain-of-function phenotype, while overexpression of a constitutively active PTPRJ phosphatase strongly reduces bacterial uptake via CEACAM3.	SIGNOR-277091
P49841	P49768	1	phosphorylation	down-regulates activity	0.586	We demonstrate that phosphorylation of serines 353 and 357 by glycogen synthase kinase-3beta (gsk3beta) induces a structural change of the hydrophilic loop of ps1the structural change of ps1 reduces the interaction with beta-catenin leading to decreased phosphorylation and ubiquitination of beta-catenin.	SIGNOR-153627
Q15475	P15311	1	transcriptional regulation	up-regulates quantity	0.342	We now show that the gene encoding Ezrin is a direct transcriptional target of Six1.	SIGNOR-259374
Q12837	Q8N100	0	transcriptional regulation	up-regulates quantity by expression	0.474	Thus, these data suggest that the expression of Brn3b can be activated directly by Math5 and that it is also subject to positive feedback regulation by Brn3 proteins.	SIGNOR-261567
P15172	P15173	1	transcriptional regulation	up-regulates quantity by expression	0.46	We conclude that MyoD is the major MRF that binds to the E-box from the myogenin promoter during differentiation.	SIGNOR-255640
O15111	P04637	1	phosphorylation	up-regulates activity	0.429	In the nucleus, IKKalpha enhances p53 mediated GADD45 and BAD gene expressions by phosphorylating p53 at Ser20 and stabilizing p53 protein levels , leading to the induction of apoptosis in response to ROS exposure.\|PKC-activated nuclear I\u03baB kinase\u03b1 promotes the stability of p53 protein and mediates reactive oxygen species-induced apoptosis [ ].	SIGNOR-280231
Q9H981	Q13315	0	phosphorylation	down-regulates activity	0.2	These findings indicate that ATM dependent phosphorylation on ARP8-S412 reduces ARP8 INO80 interaction.\|These findings raised the possibility that ATM negatively regulates the interaction of ARP8 with INO80 after etoposide treatment.	SIGNOR-279437
Q13131	P49116	1	phosphorylation	down-regulates	0.2	Tr4 transactivation is inhibited via phosphorylation bymetformin-induced amp-activated protein kinase (ampk) at the amino acid serine 351, which results in the suppression of scd1 gene expression	SIGNOR-173118
P49736	O00311	0	phosphorylation	up-regulates	0.962	In this work, by in vitro kinase reactions and mass spectrometry analysis of the products, we have mapped phosphorylation sites in the n terminus of mcm2 by cdc7, cdk2, cdk1, and ck2	SIGNOR-143984
P15529	P12931	0	phosphorylation	up-regulates activity	0.458	Src kinase phosphorylates CD46 at Y354 of the Cyt2 isoform in vitro.	SIGNOR-280127
P16949	O15264	0	phosphorylation	down-regulates	0.414	Serine 25 of oncoprotein 18 is a major cytosolic target for the mitogen-activated protein kinase.	SIGNOR-36362
Q9NS71	A6NJ46	0	transcriptional regulation	up-regulates quantity by expression	0.371	In particular, NKX6.3 transcriptional factor was found to bind specifically to the upstream sequences of GKN1, a gastric-specific tumor suppressor, and dramatically increase expression of the latter.	SIGNOR-266096
Q04206	Q06187	0	phosphorylation	up-regulates activity	0.403	Btk induces the phosphorylation of NF-\u03baB p65 which can be induced by the expression of inflammation cytokines [ ].\|Btk induces the phosphorylation of NF-\u03baB p65 which can be induced by the expression of inflammation cytokines [ xref ].	SIGNOR-280197
P52209	P06241	0	phosphorylation	up-regulates activity	0.2	6PGD is phosphorylated at tyrosine (Y) 481 by Src family kinase Fyn. This phosphorylation enhances 6PGD activity by increasing its binding affinity to NADP+ and therefore activates the PPP for NADPH and ribose-5-phosphate, which consequently detoxifies intracellular reactive oxygen species (ROS) and accelerates DNA synthesis.	SIGNOR-265758
O15111	Q86VP1	1	phosphorylation	up-regulates activity	0.383	Here we demonstrate that tax1bp1 was inducibly phosphorylated on ser593 and ser624 in response to proinflammatory stimuli. The kinase ikkalpha, but not ikkbeta, was required for phosphorylation of tax1bp1 and directly phosphorylated tax1bp1 in response to stimulation with tumor necrosis factor (tnf) or interleukin 1 (il-1).	SIGNOR-175062
Q9NTG7	P08559	1	deacetylation	down-regulates activity	0.48	SIRT3 deacetylates and increases pyruvate dehydrogenase activity in cancer cells\|SIRT3 deacetylates PDHA1 lysine 321 (K321)	SIGNOR-267636
P68400	Q13351	1	phosphorylation	up-regulates activity	0.344	Regulation of erythroid Krppel-like factor (EKLF) transcriptional activity by phosphorylation of a protein kinase casein kinase II site within its interaction domain. the transactivation capability of EKLF is augmented by co-transfection of CKIIalpha. in vitro assays demonstrate that CKIIalpha interacts with EKLF, and that the EKLF interaction domain is phosphorylated by CKII only at Thr-41	SIGNOR-241361
O15393	P59594	1	cleavage	up-regulates activity	0.2	Here, we demonstrate that SARS-CoV-2 uses the SARS-CoV receptor ACE2 for entry and the serine protease TMPRSS2 for S protein priming.	SIGNOR-260217
P46527	Q9H2X6	0	phosphorylation	up-regulates	0.254	Homeodomain-interacting protein kinase-2 stabilizes p27(kip1) by its phosphorylation at serine 10 and contributes to cell motility	SIGNOR-174617
O94768	Q15139	0	phosphorylation	up-regulates activity	0.252	Coexpression of DRAK2 and a constitutively active PKD mutant (CA-PKD1; PKD1-S738/742E) were sufficient to greatly enhance DRAK2 autophosphorylation, supporting the hypothesis that PKD catalytic activity promotes DRAK2 function.\|We note that PKD was able to phosphorylate DRAK2 outside of its C terminus, suggesting that PKD mediated phosphorylation occurs on a site in the 1-290 fragment of DRAK2.	SIGNOR-279753
Q13976	Q03393	1	phosphorylation	up-regulates	0.257	Upon expression in cos-1 cells, ptps-s19a was stable but not phosphorylated and had a reduced activity of approximately 33% in comparison to wild-type ptps. Addition of cgmp stimulated phosphotransferase activity 2-fold. Extracts from transfected cos-1 cells overexpressing cgkii stimulated ser(19) phosphorylation more than 100-fold.In assays with purified enzymes, wild-type but not ptps-s19a was a specific substrate for the cgmp-dependent protein kinase (cgk) type i and ii. Upon expression in cos-1 cells, ptps-s19a was stable but not phosphorylated and had a reduced activity of approximately 33% in comparison to wild-type ptps	SIGNOR-71680
P42229	P28482	0	phosphorylation	up-regulates	0.76	Gh treatment of chinese hamster ovary cells stably transfected with the gh receptor (choa cells) led to rapid and transient activation of both stat5a and erk1 and erk2. these observations show, for the first time, direct physical interaction between erk and stat5a and also clearly identify serine 780 as a target for erk.	SIGNOR-66239
P12272	P07288	0	cleavage	down-regulates activity	0.422	Our study demonstrates that PTHrP is a substrate for PSA. The cleavage of the amino-terminal portion of PTHrP completely disrupts its ability to interact with the PTH/PTHrP receptor and thus inhibits its PTH-like activity. \| Our data show that PSA proteolytically cleaves PTHrP (1-34) after either residue 22 or 23, generating three peptide fragments.	SIGNOR-270547
P24941	Q12959	1	phosphorylation	up-regulates	0.282	We also show that dlg1 is phosphorylated by both cdk1 and cdk2 on ser158 and ser442. These phosphorylated sites together affect the nuclear localisation of the protein, and implicate the role of phosphorylation on ser158 and ser442 in its putative nuclear functions as a tumour suppressor. phosphorylation on ser158 and ser442 enhances nuclear expression of dlg1	SIGNOR-182765
Q9H5J4	Q9NP71	0	transcriptional regulation	up-regulates quantity by expression	0.398	In this study, we clearly show that mouse and human Elovl6 are direct targets of ChREBP.	SIGNOR-267945
P46527	Q15418	0	phosphorylation	up-regulates activity	0.393	As for other PI3K effectors, RSK1 phosphorylates p27 at T198.\|RSK1 overexpression increases p27pT198, p27-cyclin D1-Cdk4 complexes, and p27 stability.	SIGNOR-279653
Q9H2K2	Q92530	1	ADP-ribosylation	down-regulates quantity by destabilization	0.496	We identify the ADP-ribosyltransferase tankyrase (TNKS) and the 19S assembly chaperones dp27 and dS5b as direct binding partners of the proteasome regulator PI31. TNKS-mediated ADP-ribosylation of PI31 drastically reduces its affinity for 20S proteasome alpha subunits to relieve 20S repression by PI31.	SIGNOR-263386
P24941	P06748	1	phosphorylation	down-regulates activity	0.561	Both subtypes of B23 proteins were phosphorylated during mitosis by cyclin B/cdc2. The RNA binding activity of B23.1 was repressed through cyclin B/cdc2-mediated phosphorylation at specific sites in B23. Thus, the RNA binding activity of B23.1 is stringently modulated by its phosphorylation and subtype association.	SIGNOR-89609
O14974	Q13464	0	phosphorylation	down-regulates activity	0.774	Phosphorylation by Rho-kinase inhibited MP activity and this reflected a decrease in V(max). Activity of MP with different substrates also was inhibited by phosphorylation. Two major sites of phosphorylation on MYPT1 were Thr(695) and Thr(850).	SIGNOR-249034
P42702	P28482	0	phosphorylation	down-regulates	0.369	Indeed, phosphorylation of the cytoplasmic domain of the low-affinity lif receptor alpha-subunit (lifr) in mono q-fractionated, lif-stimulated 3t3-l1 extracts occurred only in those fractions containing activated mapk;ser-1044 served as the major phosphorylation site in the human lifr for mapk both in agonist-stimulated 3t3-l1 lysates and by recombinant extracellular signal-regulated kinase 2 in vitro	SIGNOR-32753
Q13237	P48436	1	phosphorylation	down-regulates activity	0.501	Cyclic GMP-dependent protein kinase II inhibits cell proliferation, Sox9 expression and Akt phosphorylation in human glioma cell lines\|Prkg2 transfected glioma cell lines express a functional cGKII that can phosphorylate VASP and Sox9.	SIGNOR-278985
P31749	Q8NEB9	0	relocalization	up-regulates	0.434	One of the best characterized targets of pi3k lipid products is the protein kinase akt or protein kinase b (pkb). In quiescent cells, pkb resides in the cytosol in a low-activity conformation. Upon cellular stimulation, pkb is activated through recruitment to cellular membranes by pi3k lipid products and phosphorylation by 3h-phosphoinositide-dependent kinase-1 (pdk1).	SIGNOR-252632
Q16665	Q9UNE7	0	ubiquitination	down-regulates quantity by destabilization	0.376	the ubiquitin ligase activity of CHIP regulates HIF-1α degradation.	SIGNOR-271426
O43508	P11055	1	polyubiquitination	down-regulates quantity by destabilization	0.2	TWEAK induces ubiquitination of MyHCf and expression of atrogin-1 and MuRF1 in myotubes. our data show that TWEAK rapidly increases the conjugation of ubiquitin to MyHCf (Fig. 3A) and ubiquitination preceded the degradation of MyHCf (Fig. 2C and Fig. 3A).	SIGNOR-272628
P17612	P17542	1	phosphorylation	down-regulates	0.2	Thus, our data revealed a novel interplay between pka phosphorylation and tal1-mediated epigenetic regulation that regulates hematopoietic transcription and differentiation programs during hematopoiesis and leukemogenesis.	SIGNOR-195987
P68400	Q9HCU9	1	phosphorylation	down-regulates quantity by destabilization	0.473	We show that BRMS1 is posttranslationally regulated by TNF-induced casein kinase 2 catalytic subunit (CK2α') phosphorylation of nuclear BRMS1 on serine 30 (S30), resulting in 14-3-3ε-mediated nuclear exportation, increased BRMS1 cytosolic expression, and ubiquitin-proteasome-induced BRMS1 degradation.	SIGNOR-266407
O14733	O43353	0	phosphorylation	up-regulates activity	0.44	Collectively, the results suggest that RIPK2 binds to and activates MKK7.\|Radioactive in vitro kinase assay showed that RIPK2 can directly phosphorylate kinase-dead (K149A) MKK7 (Fig.\u00a0 xref ).	SIGNOR-280105
O75367	P38398	0	ubiquitination	up-regulates activity	0.2	BRCA1 Ubiquitinates K123 of mH2A1 in a Ligase-Activity-Dependent Manner.	SIGNOR-278752
Q92858	O60674	0	phosphorylation	up-regulates quantity	0.339	We discovered tyrosine 78 of Atoh1 is phosphorylated by a Jak2-mediated pathway only in tumor-initiating cells and in human SHH-type medulloblastoma. Phosphorylation of tyrosine 78 stabilizes Atoh1, increases Atoh1’s transcriptional activity, and is independent of canonical Jak2 signaling.	SIGNOR-262201
Q92949	Q969V4	1	transcriptional regulation	up-regulates quantity by expression	0.364	FOXJ1 expression in basal cells induced the expression of a panel of cilia-associated genes, including centrin 2 (CETN2); dynein, axonemal, heavy chain 11 (DNAH11); dynein, axonemal, intermediate chain 1 (DNAI1); dynein, axonemal, light intermediate chain 1 (DNALI1); EF-hand domain, C-terminal, containing 1 (EFHC1); sperm associated antigen 6 (SPAG6); tektin 1 (TEKT1), TEKT2 and tubulin, alpha 1a (TUBA1A; Figure 3C and Additional file 2: Table S1).	SIGNOR-266936
P12931	Q9UKT4	1	phosphorylation	up-regulates	0.324	We found that emi1 stability was regulated by phosphorylation and mutation of tyrosine 142 reduced the stability. Our data suggested bcr-abl-induced emi1 phosphorylation might be mediated by src kinase.	SIGNOR-167529
Q13164	P29590	1	phosphorylation	down-regulates activity	0.474	Big MAP kinase 1 (BMK1) also phosphorylates PML at two sites : S403 and T409.\|Mutational analysis demonstrated that BMK1 drives suppression of PML directly through its phosphorylation.	SIGNOR-279074
P21675	P52655	1	phosphorylation	up-regulates activity	0.678	Taf(ii) 250 phosphorylates human transcription factor iia on serine residues important for tbp binding and transcription activity.	SIGNOR-105688
Q14721	Q9P0L0	1	relocalization	up-regulates quantity	0.2	Confirmation that Kv2.1 and -2.2 bind VAPA and VAPB employed colocalization/redistribution, siRNA knockdown, and Förster resonance energy transfer (FRET)-based assays.\|As Kv2.1 accumulates on the surface it begins to bind ER VAPs and form the large and stable membrane junctions.	SIGNOR-262122
Q9UQ88	P21127	1	phosphorylation	up-regulates	0.305	Overall, our data indicated that thr-370 is responsible for the autophosphorylation, dimerization, and kinase activity of cdk11(p58)	SIGNOR-169628
P31751	O15111	1	phosphorylation	up-regulates	0.529	Although there are likely to be multiple levels of crosstalk between the pi3k-akt and nf-kb pathways, one mechanism has been attributed to direct phosphorylation of the amino acid residue t23 on ikb kinase alfa (ikkalfa) by akt, thereby leading to activation of this kinase upstream of nf-kb akt mediates ikkalpha phosphorylation at threonine 23 akt transiently associates in vivo with ikk and induces ikk activation. Akt mediates ikkalfa phosphorylation at threonine 23.Akt phosphorylates ikkalpha on t23, and this phosphorylation event is a prerequisite for the phosphorylation of p65 at s534 by ikkalpha and beta	SIGNOR-187010
P00533	P0DP24	1	phosphorylation	down-regulates	0.345	Phosphorylation of calmodulin by the epidermal-growth-factor-receptor tyrosine kinase. Phosphorylated calmodulin does not exhibit the characteristic ca2+ shift normally observed with calmodulin in electrophoretic gels, an observation that is consistent with this modification affecting the biological activity of the molecule.	SIGNOR-266319
P46734	Q9Y6R4	0	phosphorylation	up-regulates activity	0.639	These results, therefore, suggest that mtk1 directly phosphorylates and activates mkk3, mkk6 and sek1.	SIGNOR-50891
P60510	O75531	1	dephosphorylation	up-regulates	0.2	Herein, we demonstrate we demonstrate that phosphorylation of ser4 and/or thr2/thr3 abrogates the interaction of baf with dna and reduces its interaction with the lem domain. We have identified the major phosphatase responsible for dephosphorylation of ser-4 to be protein phosphatase 4 catalytic subunit.	SIGNOR-203281
Q13477	Q8TAU0	0	transcriptional regulation	up-regulates quantity by expression	0.428	We provide evidence that NKX2.3 can activate MAdCAM-1 transcription directly	SIGNOR-266219
P49137	P26651	1	phosphorylation	down-regulates activity	0.699	We confirm phosphorylation of TTP by MK2 and identify specific phosphorylation sites at Ser52, Ser105, Ser58, Ser176, Ser178, and Ser316. If MK2 regulates translation in part by TTP phosphorylation, TTP should be a repressor of translation when dephosphorylated and an activator of (or neutral to) translation when phosphorylated.	SIGNOR-250153
Q9UKX5	P08047	0	null	up-regulates quantity by expression	0.2	We speculate that the "mesenchymal signature" of alpha11 integrin gene expression is controlled by the activity of Sp1/Sp3, fibroblast-specific combinations of Ets family members and yet unidentified enhancer-binding transcription factors.	SIGNOR-253350
P11473	P68400	0	phosphorylation	up-regulates	0.336	Casein kinase ii (ckii) phosphorylates vdr both in vitro and in vivo at serine 208 within the hinge domain. This phosphorylation does not affect the ability of vdr to bind dna, but increases its ability to transactivate target promoters	SIGNOR-153711
Q8TE49	Q13546	1	deubiquitination	down-regulates activity	0.2	NF-kappaB Suppression by the Deubiquitinating Enzyme Cezanne\|Our study provides several lines of evidence to suggest that Cezanne suppresses TNFR signaling to NF-κB by targeting RIP1 for deubiquitination.	SIGNOR-268410
Q14164	O43734	1	phosphorylation	up-regulates activity	0.416	IKKi was required for IL-17-induced phosphorylation of Act1 on Ser311, adjacent to a putative TRAF-binding motif. Substitution of the serine at position 311 with alanine impaired the IL-17-mediated Act1-TRAF2-TRAF5 interaction and gene expression. Thus, IKKi is a kinase newly identified as modulating IL-17 signaling through its effect on Act1 phosphorylation and consequent function.	SIGNOR-262883
O60674	Q14765	1	phosphorylation	up-regulates	0.676	Janus family tyrosine kinases jak2 and tyk2, which in turn phosphorylate stat4 on tyrosine 693. The p38 mitogen-activated protein kinase (mapk) signaling pathway is also activated in response to il-12, followed by phosphorylation of stat4 on serine 721, which is required for stat4 full transcriptional activity	SIGNOR-142736
P06241	P54829	0	dephosphorylation	down-regulates	0.527	Wild-type step(61) dephosphorylates fyn at tyr(420) but not at tyr(531). These results suggest that step regulates the activity of fyn by specifically dephosphorylating the regulatory tyr(420) and may be one mechanism by which fyn activity is decreased within psds.	SIGNOR-86791
O00712	P29322	1	transcriptional regulation	up-regulates quantity	0.2	For example, within the NFI targetome, we identified 6 collagen genes, 13 genes encoding potassium channel or glutamate receptor subunits and a range of factors related to axon guidance (e.g. Slit1, Robo1, Epha4, Epha5, Epha8)	SIGNOR-268903
Q16875	P31749	0	phosphorylation	up-regulates	0.427	We also found that AMP activated protein kinase and protein kinases A, B, and C catalyzed the phosphorylation of Ser-460 of HBP1, and that in addition both isoforms are phosphorylated at a second, as yet undetermined site by protein kinase C. However, none of the phosphorylations had any effect on the intrinsic kinetic characteristics of either enzymatic activity, and neither did point mutation (mimicking phosphorylation), deletion, and alternative-splice modification of the HBP1 carboxy-terminal region. Instead, these phosphorylations and mutations decreased the sensitivity of the 6PF2K to a potent allosteric inhibitor, phosphoenolpyruvate, which appears to be the major regulatory mechanism.	SIGNOR-252477
P68400	P27540	1	phosphorylation	down-regulates	0.34	Here, we show that arnt and alt arnt proteins are differentially phosphorylated by protein kinase ckii in vitro. Phosphorylation had an inhibitory effect on dna-binding to an e-box probe by alt arnt, but not arnt, homodimers. This inhibitory phosphorylation occurs through ser77.	SIGNOR-140034
P09917	P27361	0	phosphorylation	up-regulates activity	0.328	Intriguingly, a significant difference in the potency of nonredox-type inhibitors (but not of BWA4C) was determined between wild-type 5-LO and the mutant S271A/S663A-5-LO (lacking phosphorylation sites for ERK1/2 and MAPKAPK-2) in HeLa cells. Collectively, our data suggest that compared with Ca2+-mediated 5-LO product formation, enzyme activation involving 5-LO phosphorylation events specifically and strongly alters the susceptibility of 5-LO toward nonredox-type inhibitors in intact cells.	SIGNOR-264440
Q16539	Q06413	1	phosphorylation	up-regulates activity	0.696	We found that in monocytic cells, lps increases the transactivation activity of mef2c through p38-catalysed phosphorylation.	SIGNOR-47136
Q16539	P04637	1	phosphorylation	up-regulates activity	0.773	P38 regulates p53, but also in p53-defective tumor cells rewire their checkpoint response and become dependent in the p38/mk2 pathway in mcf-7 cells, p38 kinase activated p53 more effectively than other members of the ras pathway. p53 and p38 kinase exist in the same physical complex, and co-expression of p38 stabilized p53 protein. In vitro, p38 kinase phosphorylated p53 at ser33 and ser46, a newly identified site.	SIGNOR-155246
Q13114	P49674	0	phosphorylation	up-regulates activity	0.307	CK1ɛ interacted with and phosphorylated TRAF3 at Ser349, which thereby promoted the Lys63 (K63)-linked ubiquitination of TRAF3 and subsequent recruitment of the kinase TBK1 to TRAF3.	SIGNOR-277212
Q13535	P50549	1	phosphorylation	up-regulates quantity by stabilization	0.2	Collectively, the results described above indicate that ATR phosphorylates ETV1 and stabilizes it from proteolytic degradation.	SIGNOR-279355
P12931	Q06124	0	dephosphorylation	up-regulates activity	0.653	Several protein tyrosine phosphatases are capable of activating Src by dephosphorylating Y530 (reviewed in ref. 9). These include PTP-α, PTP-λ, SHP-1, SHP-2, and PTP1B	SIGNOR-248671
Q16873	P23443	0	phosphorylation	down-regulates activity	0.2	Here, we identified Ser(36) as the major p70S6k phosphorylation site, along with a low frequency site at Thr(40), using an in vitro phosphorylation assay combined with mass spectrometry. Cellular LTC4S activity is suppressed by PKC-mediated phosphorylation, and recently a downstream p70S6k was shown to play an important role in this process.	SIGNOR-277256
P10275	Q9NQU5	0	phosphorylation	down-regulates quantity by destabilization	0.2	Furthermore, AR phosphorylation at Ser-578 by PAK6 promotes AR-E3 ligase murine double minute-2 (Mdm2) association, causing AR degradation upon androgen stimuli.	SIGNOR-279247
P45984	P54259	1	phosphorylation	down-regulates activity	0.2	Dentatorubral-pallidoluysian atrophy protein is phosphorylated by c-jun nh2-terminal kinase. serine 734 of the drpla protein is a phospho-acceptor site by jnk. The phosphorylation may be coupled to the activation of a protease. The molecular size of drpla protein detected in the rat brain with the specific phosphopeptide antibody was 150_kda, which was slightly smaller than that expected from the sequence and the results with the human protein. The phosphorylated forms of ha-tagged human drpla gradually disappeared after osmotic treatment,	SIGNOR-102402
P23528	P53671	0	phosphorylation	down-regulates activity	0.766	We report here that limk1 and limk2 phosphorylate both cofilin and actin-depolymerizing factor (adf) specifically at ser-3 and exhibit partially distinct substrate specificity when tested using site-directed cofilin mutants as substrates	SIGNOR-105098
O96017	Q13263	1	phosphorylation	down-regulates activity	0.411	In particular, Chk2 phosphorylates KAP1 on Ser473 decreasing the interaction between KAP1 and HP1 proteins: this post translational modification promotes HP1\u03b2 mobilization and the reorganization of chromatin structure favoring the repair of DNA breaks inside heterochromatin [ , ].\|Of note, phosphorylation of S473 by Chk2 decreases the interaction between KAP1 and HP1 proteins and is necessary for HP1\u03b2 mobilization, a key event for DNA repair in the heterochromatin [ - ].	SIGNOR-279730
Q92918	P00519	0	phosphorylation	up-regulates activity	0.379	C-Abl phosphorylates HPK1 in cytoplasm and stimulates HPK1 activity. the c-Abl phosphorylation site (YXXP) in HPK1 (Y232QPP; aa 232–235) is localized in HPK1-KD	SIGNOR-251429
P02818	P15036	0	transcriptional regulation	up-regulates quantity by expression	0.2	Ets2 is expressed at high levels during the differentiation and matrix mineralization phases of MC3T3-E1 culture. In addition, several extracellular matrix (ECM) associated gene products are targets of Ets2. Some of these matrix associated genes include: bone sialoprotein, osteonectin, osteocalcin and osteopontin	SIGNOR-259875
Q9UNE7	Q9BXL7	1	ubiquitination	up-regulates activity	0.327	Subsequently, the ubiquitination of CARMA1 catalyzed by STUB1 was identified as Lys 27 linked, which is important for CARMA1 mediated NF-kappaB activation.	SIGNOR-278720
Q02535	Q14289	0	phosphorylation	up-regulates quantity	0.2	Taken together these findings demonstrated that Pyk2 mediates the expression of ID3 protein.\|Together these findings from the combined MS+MS/MS data confirm that Flag tagged ID3 is phosphorylated by active recombinant Pyk2 kinase; and support the phospho-Tyr band that was detected at the corresponding MW ~ 13 kDA for Flag-ID3 by immunoblot.	SIGNOR-278496
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
P19429	P17612	0	phosphorylation	up-regulates activity	0.423	Phosphorylation at ser 23/24 (e.g., by pka or pkg) results in reduction in myofilament ca2+ sensitivity and an increase in crossbridge cycling rate, leading to acceleration of relaxation and an increase in power output but a reduced economy of contraction. Conversely, phosphorylation at ser 43/45 (by pkc) is associated with reduced maximum ca2+-activated force and decreased crossbridge cycling rates, which are likely to reduce power output and delay relaxation, with an increased economy of contraction.	SIGNOR-134605
P04183	P24941	0	phosphorylation	down-regulates	0.296	Given that the dimeric form of tk1 is less active than the tetrameric, we propose that mitotic phosphorylation of serine-13 is of physiological importance, in that it may counteract atp-dependent activation of tk1 by affecting its quaternary structure, thus attenuating its enzymatic function at the g2/m phase.	SIGNOR-95578
Q9BZS1	P26358	0	transcriptional regulation	down-regulates quantity by repression	0.488	Our results showed that arsenic induced the high expression of DNMT1 and Foxp3 gene promoter methylation level, thereby inhibiting the expression levels of Foxp3, followed by decreasing Tregs and reducing related anti-inflammatory cytokines, such as interleukin 10 (IL-10) and interleukin 10 (IL-35)	SIGNOR-269053
P01106	Q13485	0	transcriptional regulation	down-regulates quantity by repression	0.64	Down-regulation of c-Myc is a critical event for growth inhibition induced by transforming growth factor-β (TGF-β) and is frequently impaired in cancer cells. We determined a Smad-responsive element in the c-mycpromoter.	SIGNOR-251493
P49810	Q14790	0	cleavage	up-regulates activity	0.332	In decreasing order of activity, caspase-8, -3, -1, -6 and -7 proteolysed PS2 at the recognition site D326SYD329.	SIGNOR-261752
Q7Z6B7	P63000	1	gtpase-activating protein	down-regulates activity	0.56	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-260515
P04001	Q92753	0	transcriptional regulation	up-regulates quantity by expression	0.2	These observations indicate that RORβ is required for the induction of S opsin and support the conclusion that RORβ regulates Opn1sw transcription in a direct manner through ROREs within its proximal promoter region. In addition, they explain the greatly diminished expression of Opn1sw observed in the retina of RORβ-/- mice.	SIGNOR-266851
P42345	Q96EB6	1	phosphorylation	down-regulates activity	0.551	These results demonstrate that the inhibition of SIRT1 by mTOR fosters survival of DNA damage-induced prematurely senescent squamous cell carcinoma cells via Bfl-1/A1 in the absence of functional p53.\|This process involved the mTOR-dependent phosphorylation of SIRT1 at serine 47, resulting in the inhibition of the deacetylase activity of SIRT1.	SIGNOR-280047

Q9Y5X1

Q07912

0

phosphorylation

up-regulates

0.505

We have previously shown that sh3px1, phosphorylated by ack2 (activated cdc42-associated tyrosine kinase 2), regulates the degradation of egf (epidermal growth factor) receptor.

SIGNOR-142569

P62136

P06493

0

phosphorylation

down-regulates activity

0.575

Both of these pp1 isoforms contain an arg-pro-ile/val-thr-pro-pro-arg sequence near the c terminus, a known site of phosphorylation by cdc/cdk kinases, and phosphorylation attenuates phosphatase activity.

SIGNOR-151799

P10070

Q6PHR2

0

phosphorylation

up-regulates activity

0.621

We show that ULK3 is able to phosphorylate three mammalian GLI proteins in vitro

SIGNOR-260798

P49841

Q00653

1

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

P55212

P59595

1

cleavage

up-regulates activity

0.2

Caspase-6 is activated through the intrinsic pathway and mediates C-terminal cleavage of SARS-CoV N at residues 400 and 403

SIGNOR-260212

P17612

P48436

1

phosphorylation

up-regulates

0.465

We find that activation of camp-dependent protein kinase a (pka) induces phosphorylation of sox9 on its two s64 and s181 pka sites, and its nuclear localization by enhancing sox9 binding to the nucleocytoplasmic transport protein importin beta.

SIGNOR-137085

Q8IYT8

Q9Y478

1

phosphorylation

down-regulates

0.329

Ulk1/2 in turn phosphorylates all three subunits of ampk and thereby negatively regulates its activity

SIGNOR-173092

P06493

P22314

1

phosphorylation

up-regulates

0.405

Ubiquitin-activating enzyme, e1, is phosphorylated in mammalian cells by the protein kinase cdc2. Each serine residue was independently mutated to an alanine and analyzed by two-dimensional electrophoresis;only serine 4 was phosphorylated. Disruption of the basic amino acids within the nls resulted in loss of exclusive nuclear localization and a 90-95% decrease in the phosphorylation of ha1-e1

SIGNOR-31157

O95295

O43567

0

polyubiquitination

up-regulates activity

0.521

RNF13 directly interacted with snapin, a SNAP-25-interacting protein. Interestingly, snapin was ubiquitinated by RNF13 via the lysine-29 conjugated polyubiquitin chain, which in turn promoted the association of snapin with SNAP-25. Consistently, we found an attenuated interaction between snapin and SNAP-25 in the RNF13-null mice. Therefore, these results suggest that RNF13 is involved in the regulation of the SNARE complex, which thereby controls synaptic function.

SIGNOR-272044

P63104

Q05655

0

phosphorylation

down-regulates activity

0.446

We confirmed that MAPKAPK2 interacted with and phosphorylated 14-3-3zeta in vitro and in HEK293 cells. | Experimentally, S58D mutation significantly impaired both 14-3-3zeta dimerization and binding to Raf-1.

SIGNOR-249222

Q14847

P05771

0

phosphorylation

down-regulates activity

0.2

Actin binding of human lim and sh3 protein is regulated by cgmp- and camp-dependent protein kinase phosphorylation on serine 146. Phosphorylation of lasp at ser-146 leads to a redistribution of the actin-bound protein from the tips of the cell membrane to the cytosol, accompanied with a reduced cell migration

SIGNOR-97942

P46937

Q9Y297

0

ubiquitination

down-regulates

0.544

This cascade of phosphorylation allows the binding of scfbetatrcp that promotes the ubiquitination and degradation of yap.

SIGNOR-201138

O95630

Q9HAU4

0

polyubiquitination

down-regulates quantity by destabilization

0.529

RNF11 recruits AMSH to Smurf2 E3 ligase. Smurf2 promotes ubiquitination of AMSH in the presence of wt RNF11. Previously, we have shown that RNF11 interacts with the HECT-type E3 ligases AIP4 and Smurf2. Here, we show that RNF11 binds to AMSH in mammalian cells and that this interaction is independent of the RNF11 RING-finger domain and the PY motif. Our results also demonstrate that AMSH is ubiquitinated by Smurf2 E3 ligase in the presence of RNF11 and that a consequent reduction in its steady-state level requires both RNF11 and Smurf2. RNF11 therefore recruits AMSH to Smurf2 for ubiquitination, leading to its degradation by the 26S proteasome.

SIGNOR-272951

O95140

Q9BXM7

0

phosphorylation

down-regulates quantity

0.81

If PINK1 is responsible for the degradation of Mfn2, then silencing PINK1 should induce mitochondrial fusion by upregulating Mfn2 expression.|We show that downregulation of Mfn2 is induced by proteasomal degradation triggered by PINK1, which phosphorylates Mfn2 at S442.

SIGNOR-278208

Q93009

P62979

1

cleavage

up-regulates quantity

0.654

Here we provide data suggesting that two of the four mammalian ubiquitin precursors, UBA52 and UBA80, are processed mostly post-translationally whereas the other two, UBB and UBC, probably undergo a combination of co- and post-translational processing. Using an unbiased biochemical approach we found that UCHL3, USP9X, USP7, USP5 and Otulin/Gumby/FAM105b are by far the most active DUBs acting on these precursors.

SIGNOR-270824

P11831

Q05655

0

phosphorylation

down-regulates activity

0.2

Protein kinase C delta blocks immediate-early gene expression in senescent cells by inactivating serum response factor.|The phosphorylation of T160 of SRF by PKC delta in vitro and in vivo led to loss of SRF DNA binding activity.

SIGNOR-279347

P40198

Q12913

0

dephosphorylation

down-regulates activity

0.387

We also determined that recombinant PTPRJ directly dephosphorylates the cytoplasmic tyrosine residues of purified full-length CEACAM3 and recognizes synthetic CEACAM3-derived phospho-peptides as substrates.|We show depletion of PTPRJ results in a gain-of-function phenotype, while overexpression of a constitutively active PTPRJ phosphatase strongly reduces bacterial uptake via CEACAM3.

SIGNOR-277091

P49841

P49768

1

phosphorylation

down-regulates activity

0.586

We demonstrate that phosphorylation of serines 353 and 357 by glycogen synthase kinase-3beta (gsk3beta) induces a structural change of the hydrophilic loop of ps1the structural change of ps1 reduces the interaction with beta-catenin leading to decreased phosphorylation and ubiquitination of beta-catenin.

SIGNOR-153627

Q15475

P15311

1

transcriptional regulation

up-regulates quantity

0.342

We now show that the gene encoding Ezrin is a direct transcriptional target of Six1.

SIGNOR-259374

Q12837

Q8N100

0

transcriptional regulation

up-regulates quantity by expression

0.474

Thus, these data suggest that the expression of Brn3b can be activated directly by Math5 and that it is also subject to positive feedback regulation by Brn3 proteins.

SIGNOR-261567

P15172

P15173

1

transcriptional regulation

up-regulates quantity by expression

0.46

We conclude that MyoD is the major MRF that binds to the E-box from the myogenin promoter during differentiation.

SIGNOR-255640

O15111

P04637

1

phosphorylation

up-regulates activity

0.429

In the nucleus, IKKalpha enhances p53 mediated GADD45 and BAD gene expressions by phosphorylating p53 at Ser20 and stabilizing p53 protein levels , leading to the induction of apoptosis in response to ROS exposure.|PKC-activated nuclear I\u03baB kinase\u03b1 promotes the stability of p53 protein and mediates reactive oxygen species-induced apoptosis [ ].

SIGNOR-280231

Q9H981

Q13315

0

phosphorylation

down-regulates activity

0.2

These findings indicate that ATM dependent phosphorylation on ARP8-S412 reduces ARP8 INO80 interaction.|These findings raised the possibility that ATM negatively regulates the interaction of ARP8 with INO80 after etoposide treatment.

SIGNOR-279437

Q13131

P49116

1

phosphorylation

down-regulates

0.2

Tr4 transactivation is inhibited via phosphorylation bymetformin-induced amp-activated protein kinase (ampk) at the amino acid serine 351, which results in the suppression of scd1 gene expression

SIGNOR-173118

P49736

O00311

0

phosphorylation

up-regulates

0.962

In this work, by in vitro kinase reactions and mass spectrometry analysis of the products, we have mapped phosphorylation sites in the n terminus of mcm2 by cdc7, cdk2, cdk1, and ck2

SIGNOR-143984

P15529

P12931

0

phosphorylation

up-regulates activity

0.458

Src kinase phosphorylates CD46 at Y354 of the Cyt2 isoform in vitro.

SIGNOR-280127

P16949

O15264

0

phosphorylation

down-regulates

0.414

Serine 25 of oncoprotein 18 is a major cytosolic target for the mitogen-activated protein kinase.

SIGNOR-36362

Q9NS71

A6NJ46

0

transcriptional regulation

up-regulates quantity by expression

0.371

In particular, NKX6.3 transcriptional factor was found to bind specifically to the upstream sequences of GKN1, a gastric-specific tumor suppressor, and dramatically increase expression of the latter.

SIGNOR-266096

Q04206

Q06187

0

phosphorylation

up-regulates activity

0.403

Btk induces the phosphorylation of NF-\u03baB p65 which can be induced by the expression of inflammation cytokines [ ].|Btk induces the phosphorylation of NF-\u03baB p65 which can be induced by the expression of inflammation cytokines [ xref ].

SIGNOR-280197

P52209

P06241

0

phosphorylation

up-regulates activity

0.2

6PGD is phosphorylated at tyrosine (Y) 481 by Src family kinase Fyn. This phosphorylation enhances 6PGD activity by increasing its binding affinity to NADP+ and therefore activates the PPP for NADPH and ribose-5-phosphate, which consequently detoxifies intracellular reactive oxygen species (ROS) and accelerates DNA synthesis.

SIGNOR-265758

O15111

Q86VP1

1

phosphorylation

up-regulates activity

0.383

Here we demonstrate that tax1bp1 was inducibly phosphorylated on ser593 and ser624 in response to proinflammatory stimuli. The kinase ikkalpha, but not ikkbeta, was required for phosphorylation of tax1bp1 and directly phosphorylated tax1bp1 in response to stimulation with tumor necrosis factor (tnf) or interleukin 1 (il-1).

SIGNOR-175062

Q9NTG7

P08559

1

deacetylation

down-regulates activity

0.48

SIRT3 deacetylates and increases pyruvate dehydrogenase activity in cancer cells|SIRT3 deacetylates PDHA1 lysine 321 (K321)

SIGNOR-267636

P68400

Q13351

1

phosphorylation

up-regulates activity

0.344

Regulation of erythroid Krppel-like factor (EKLF) transcriptional activity by phosphorylation of a protein kinase casein kinase II site within its interaction domain. the transactivation capability of EKLF is augmented by co-transfection of CKIIalpha. in vitro assays demonstrate that CKIIalpha interacts with EKLF, and that the EKLF interaction domain is phosphorylated by CKII only at Thr-41

SIGNOR-241361

O15393

P59594

1

cleavage

up-regulates activity

0.2

Here, we demonstrate that SARS-CoV-2 uses the SARS-CoV receptor ACE2 for entry and the serine protease TMPRSS2 for S protein priming.

SIGNOR-260217

P46527

Q9H2X6

0

phosphorylation

up-regulates

0.254

Homeodomain-interacting protein kinase-2 stabilizes p27(kip1) by its phosphorylation at serine 10 and contributes to cell motility

SIGNOR-174617

O94768

Q15139

0

phosphorylation

up-regulates activity

0.252

Coexpression of DRAK2 and a constitutively active PKD mutant (CA-PKD1; PKD1-S738/742E) were sufficient to greatly enhance DRAK2 autophosphorylation, supporting the hypothesis that PKD catalytic activity promotes DRAK2 function.|We note that PKD was able to phosphorylate DRAK2 outside of its C terminus, suggesting that PKD mediated phosphorylation occurs on a site in the 1-290 fragment of DRAK2.

SIGNOR-279753

Q13976

Q03393

1

phosphorylation

up-regulates

0.257

Upon expression in cos-1 cells, ptps-s19a was stable but not phosphorylated and had a reduced activity of approximately 33% in comparison to wild-type ptps. Addition of cgmp stimulated phosphotransferase activity 2-fold. Extracts from transfected cos-1 cells overexpressing cgkii stimulated ser(19) phosphorylation more than 100-fold.In assays with purified enzymes, wild-type but not ptps-s19a was a specific substrate for the cgmp-dependent protein kinase (cgk) type i and ii. Upon expression in cos-1 cells, ptps-s19a was stable but not phosphorylated and had a reduced activity of approximately 33% in comparison to wild-type ptps

SIGNOR-71680

P42229

P28482

0

phosphorylation

up-regulates

0.76

Gh treatment of chinese hamster ovary cells stably transfected with the gh receptor (choa cells) led to rapid and transient activation of both stat5a and erk1 and erk2. these observations show, for the first time, direct physical interaction between erk and stat5a and also clearly identify serine 780 as a target for erk.

SIGNOR-66239

P12272

P07288

0

cleavage

down-regulates activity

0.422

Our study demonstrates that PTHrP is a substrate for PSA. The cleavage of the amino-terminal portion of PTHrP completely disrupts its ability to interact with the PTH/PTHrP receptor and thus inhibits its PTH-like activity. | Our data show that PSA proteolytically cleaves PTHrP (1-34) after either residue 22 or 23, generating three peptide fragments.

SIGNOR-270547

P24941

Q12959

1

phosphorylation

up-regulates

0.282

We also show that dlg1 is phosphorylated by both cdk1 and cdk2 on ser158 and ser442. These phosphorylated sites together affect the nuclear localisation of the protein, and implicate the role of phosphorylation on ser158 and ser442 in its putative nuclear functions as a tumour suppressor. phosphorylation on ser158 and ser442 enhances nuclear expression of dlg1

SIGNOR-182765

Q9H5J4

Q9NP71

0

transcriptional regulation

up-regulates quantity by expression

0.398

In this study, we clearly show that mouse and human Elovl6 are direct targets of ChREBP.

SIGNOR-267945

P46527

Q15418

0

phosphorylation

up-regulates activity

0.393

As for other PI3K effectors, RSK1 phosphorylates p27 at T198.|RSK1 overexpression increases p27pT198, p27-cyclin D1-Cdk4 complexes, and p27 stability.

SIGNOR-279653

Q9H2K2

Q92530

1

ADP-ribosylation

down-regulates quantity by destabilization

0.496

We identify the ADP-ribosyltransferase tankyrase (TNKS) and the 19S assembly chaperones dp27 and dS5b as direct binding partners of the proteasome regulator PI31. TNKS-mediated ADP-ribosylation of PI31 drastically reduces its affinity for 20S proteasome alpha subunits to relieve 20S repression by PI31.

SIGNOR-263386

P24941

P06748

1

phosphorylation

down-regulates activity

0.561

Both subtypes of B23 proteins were phosphorylated during mitosis by cyclin B/cdc2. The RNA binding activity of B23.1 was repressed through cyclin B/cdc2-mediated phosphorylation at specific sites in B23. Thus, the RNA binding activity of B23.1 is stringently modulated by its phosphorylation and subtype association.

SIGNOR-89609

O14974

Q13464

0

phosphorylation

down-regulates activity

0.774

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

SIGNOR-249034

P42702

P28482

0

phosphorylation

down-regulates

0.369

Indeed, phosphorylation of the cytoplasmic domain of the low-affinity lif receptor alpha-subunit (lifr) in mono q-fractionated, lif-stimulated 3t3-l1 extracts occurred only in those fractions containing activated mapk;ser-1044 served as the major phosphorylation site in the human lifr for mapk both in agonist-stimulated 3t3-l1 lysates and by recombinant extracellular signal-regulated kinase 2 in vitro

SIGNOR-32753

Q13237

P48436

1

phosphorylation

down-regulates activity

0.501

Cyclic GMP-dependent protein kinase II inhibits cell proliferation, Sox9 expression and Akt phosphorylation in human glioma cell lines|Prkg2 transfected glioma cell lines express a functional cGKII that can phosphorylate VASP and Sox9.

SIGNOR-278985

P31749

Q8NEB9

0

relocalization

up-regulates

0.434

One of the best characterized targets of pi3k lipid products is the protein kinase akt or protein kinase b (pkb). In quiescent cells, pkb resides in the cytosol in a low-activity conformation. Upon cellular stimulation, pkb is activated through recruitment to cellular membranes by pi3k lipid products and phosphorylation by 3h-phosphoinositide-dependent kinase-1 (pdk1).

SIGNOR-252632

Q16665

Q9UNE7

0

ubiquitination

down-regulates quantity by destabilization

0.376

the ubiquitin ligase activity of CHIP regulates HIF-1α degradation.

SIGNOR-271426

O43508

P11055

1

polyubiquitination

down-regulates quantity by destabilization

0.2

TWEAK induces ubiquitination of MyHCf and expression of atrogin-1 and MuRF1 in myotubes. our data show that TWEAK rapidly increases the conjugation of ubiquitin to MyHCf (Fig. 3A) and ubiquitination preceded the degradation of MyHCf (Fig. 2C and Fig. 3A).

SIGNOR-272628

P17612

P17542

1

phosphorylation

down-regulates

0.2

Thus, our data revealed a novel interplay between pka phosphorylation and tal1-mediated epigenetic regulation that regulates hematopoietic transcription and differentiation programs during hematopoiesis and leukemogenesis.

SIGNOR-195987

P68400

Q9HCU9

1

phosphorylation

down-regulates quantity by destabilization

0.473

We show that BRMS1 is posttranslationally regulated by TNF-induced casein kinase 2 catalytic subunit (CK2α') phosphorylation of nuclear BRMS1 on serine 30 (S30), resulting in 14-3-3ε-mediated nuclear exportation, increased BRMS1 cytosolic expression, and ubiquitin-proteasome-induced BRMS1 degradation.

SIGNOR-266407

O14733

O43353

0

phosphorylation

up-regulates activity

0.44

Collectively, the results suggest that RIPK2 binds to and activates MKK7.|Radioactive in vitro kinase assay showed that RIPK2 can directly phosphorylate kinase-dead (K149A) MKK7 (Fig.\u00a0 xref ).

SIGNOR-280105

O75367

P38398

0

ubiquitination

up-regulates activity

0.2

BRCA1 Ubiquitinates K123 of mH2A1 in a Ligase-Activity-Dependent Manner.

SIGNOR-278752

Q92858

O60674

0

phosphorylation

up-regulates quantity

0.339

We discovered tyrosine 78 of Atoh1 is phosphorylated by a Jak2-mediated pathway only in tumor-initiating cells and in human SHH-type medulloblastoma. Phosphorylation of tyrosine 78 stabilizes Atoh1, increases Atoh1’s transcriptional activity, and is independent of canonical Jak2 signaling.

SIGNOR-262201

Q92949

Q969V4

1

transcriptional regulation

up-regulates quantity by expression

0.364

FOXJ1 expression in basal cells induced the expression of a panel of cilia-associated genes, including centrin 2 (CETN2); dynein, axonemal, heavy chain 11 (DNAH11); dynein, axonemal, intermediate chain 1 (DNAI1); dynein, axonemal, light intermediate chain 1 (DNALI1); EF-hand domain, C-terminal, containing 1 (EFHC1); sperm associated antigen 6 (SPAG6); tektin 1 (TEKT1), TEKT2 and tubulin, alpha 1a (TUBA1A; Figure 3C and Additional file 2: Table S1).

SIGNOR-266936

P12931

Q9UKT4

1

phosphorylation

up-regulates

0.324

We found that emi1 stability was regulated by phosphorylation and mutation of tyrosine 142 reduced the stability. Our data suggested bcr-abl-induced emi1 phosphorylation might be mediated by src kinase.

SIGNOR-167529

Q13164

P29590

1

phosphorylation

down-regulates activity

0.474

Big MAP kinase 1 (BMK1) also phosphorylates PML at two sites : S403 and T409.|Mutational analysis demonstrated that BMK1 drives suppression of PML directly through its phosphorylation.

SIGNOR-279074

P21675

P52655

1

phosphorylation

up-regulates activity

0.678

Taf(ii) 250 phosphorylates human transcription factor iia on serine residues important for tbp binding and transcription activity.

SIGNOR-105688

Q14721

Q9P0L0

1

relocalization

up-regulates quantity

0.2

Confirmation that Kv2.1 and -2.2 bind VAPA and VAPB employed colocalization/redistribution, siRNA knockdown, and Förster resonance energy transfer (FRET)-based assays.|As Kv2.1 accumulates on the surface it begins to bind ER VAPs and form the large and stable membrane junctions.

SIGNOR-262122

Q9UQ88

P21127

1

phosphorylation

up-regulates

0.305

Overall, our data indicated that thr-370 is responsible for the autophosphorylation, dimerization, and kinase activity of cdk11(p58)

SIGNOR-169628

P31751

O15111

1

phosphorylation

up-regulates

0.529

Although there are likely to be multiple levels of crosstalk between the pi3k-akt and nf-kb pathways, one mechanism has been attributed to direct phosphorylation of the amino acid residue t23 on ikb kinase alfa (ikkalfa) by akt, thereby leading to activation of this kinase upstream of nf-kb akt mediates ikkalpha phosphorylation at threonine 23 akt transiently associates in vivo with ikk and induces ikk activation. Akt mediates ikkalfa phosphorylation at threonine 23.Akt phosphorylates ikkalpha on t23, and this phosphorylation event is a prerequisite for the phosphorylation of p65 at s534 by ikkalpha and beta

SIGNOR-187010

P00533

P0DP24

1

phosphorylation

down-regulates

0.345

Phosphorylation of calmodulin by the epidermal-growth-factor-receptor tyrosine kinase. Phosphorylated calmodulin does not exhibit the characteristic ca2+ shift normally observed with calmodulin in electrophoretic gels, an observation that is consistent with this modification affecting the biological activity of the molecule.

SIGNOR-266319

P46734

Q9Y6R4

0

phosphorylation

up-regulates activity

0.639

These results, therefore, suggest that mtk1 directly phosphorylates and activates mkk3, mkk6 and sek1.

SIGNOR-50891

P60510

O75531

1

dephosphorylation

up-regulates

0.2

Herein, we demonstrate we demonstrate that phosphorylation of ser4 and/or thr2/thr3 abrogates the interaction of baf with dna and reduces its interaction with the lem domain. We have identified the major phosphatase responsible for dephosphorylation of ser-4 to be protein phosphatase 4 catalytic subunit.

SIGNOR-203281

Q13477

Q8TAU0

0

transcriptional regulation

up-regulates quantity by expression

0.428

We provide evidence that NKX2.3 can activate MAdCAM-1 transcription directly

SIGNOR-266219

P49137

P26651

1

phosphorylation

down-regulates activity

0.699

We confirm phosphorylation of TTP by MK2 and identify specific phosphorylation sites at Ser52, Ser105, Ser58, Ser176, Ser178, and Ser316. If MK2 regulates translation in part by TTP phosphorylation, TTP should be a repressor of translation when dephosphorylated and an activator of (or neutral to) translation when phosphorylated.

SIGNOR-250153

Q9UKX5

P08047

0

null

up-regulates quantity by expression

0.2

We speculate that the "mesenchymal signature" of alpha11 integrin gene expression is controlled by the activity of Sp1/Sp3, fibroblast-specific combinations of Ets family members and yet unidentified enhancer-binding transcription factors.

SIGNOR-253350

P11473

P68400

0

phosphorylation

up-regulates

0.336

Casein kinase ii (ckii) phosphorylates vdr both in vitro and in vivo at serine 208 within the hinge domain. This phosphorylation does not affect the ability of vdr to bind dna, but increases its ability to transactivate target promoters

SIGNOR-153711

Q8TE49

Q13546

1

deubiquitination

down-regulates activity

0.2

NF-kappaB Suppression by the Deubiquitinating Enzyme Cezanne|Our study provides several lines of evidence to suggest that Cezanne suppresses TNFR signaling to NF-κB by targeting RIP1 for deubiquitination.

SIGNOR-268410

Q14164

O43734

1

phosphorylation

up-regulates activity

0.416

IKKi was required for IL-17-induced phosphorylation of Act1 on Ser311, adjacent to a putative TRAF-binding motif. Substitution of the serine at position 311 with alanine impaired the IL-17-mediated Act1-TRAF2-TRAF5 interaction and gene expression. Thus, IKKi is a kinase newly identified as modulating IL-17 signaling through its effect on Act1 phosphorylation and consequent function.

SIGNOR-262883

O60674

Q14765

1

phosphorylation

up-regulates

0.676

Janus family tyrosine kinases jak2 and tyk2, which in turn phosphorylate stat4 on tyrosine 693. The p38 mitogen-activated protein kinase (mapk) signaling pathway is also activated in response to il-12, followed by phosphorylation of stat4 on serine 721, which is required for stat4 full transcriptional activity

SIGNOR-142736

P06241

P54829

0

dephosphorylation

down-regulates

0.527

Wild-type step(61) dephosphorylates fyn at tyr(420) but not at tyr(531). These results suggest that step regulates the activity of fyn by specifically dephosphorylating the regulatory tyr(420) and may be one mechanism by which fyn activity is decreased within psds.

SIGNOR-86791

O00712

P29322

1

transcriptional regulation

up-regulates quantity

0.2

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

SIGNOR-268903

Q16875

P31749

0

phosphorylation

up-regulates

0.427

We also found that AMP activated protein kinase and protein kinases A, B, and C catalyzed the phosphorylation of Ser-460 of HBP1, and that in addition both isoforms are phosphorylated at a second, as yet undetermined site by protein kinase C. However, none of the phosphorylations had any effect on the intrinsic kinetic characteristics of either enzymatic activity, and neither did point mutation (mimicking phosphorylation), deletion, and alternative-splice modification of the HBP1 carboxy-terminal region. Instead, these phosphorylations and mutations decreased the sensitivity of the 6PF2K to a potent allosteric inhibitor, phosphoenolpyruvate, which appears to be the major regulatory mechanism.

SIGNOR-252477

P68400

P27540

1

phosphorylation

down-regulates

0.34

Here, we show that arnt and alt arnt proteins are differentially phosphorylated by protein kinase ckii in vitro. Phosphorylation had an inhibitory effect on dna-binding to an e-box probe by alt arnt, but not arnt, homodimers. This inhibitory phosphorylation occurs through ser77.

SIGNOR-140034

P09917

P27361

0

phosphorylation

up-regulates activity

0.328

Intriguingly, a significant difference in the potency of nonredox-type inhibitors (but not of BWA4C) was determined between wild-type 5-LO and the mutant S271A/S663A-5-LO (lacking phosphorylation sites for ERK1/2 and MAPKAPK-2) in HeLa cells. Collectively, our data suggest that compared with Ca2+-mediated 5-LO product formation, enzyme activation involving 5-LO phosphorylation events specifically and strongly alters the susceptibility of 5-LO toward nonredox-type inhibitors in intact cells.

SIGNOR-264440

Q16539

Q06413

1

phosphorylation

up-regulates activity

0.696

We found that in monocytic cells, lps increases the transactivation activity of mef2c through p38-catalysed phosphorylation.

SIGNOR-47136

Q16539

P04637

1

phosphorylation

up-regulates activity

0.773

P38 regulates p53, but also in p53-defective tumor cells rewire their checkpoint response and become dependent in the p38/mk2 pathway in mcf-7 cells, p38 kinase activated p53 more effectively than other members of the ras pathway. p53 and p38 kinase exist in the same physical complex, and co-expression of p38 stabilized p53 protein. In vitro, p38 kinase phosphorylated p53 at ser33 and ser46, a newly identified site.

SIGNOR-155246

Q13114

P49674

0

phosphorylation

up-regulates activity

0.307

CK1ɛ interacted with and phosphorylated TRAF3 at Ser349, which thereby promoted the Lys63 (K63)-linked ubiquitination of TRAF3 and subsequent recruitment of the kinase TBK1 to TRAF3.

SIGNOR-277212

Q13535

P50549

1

phosphorylation

up-regulates quantity by stabilization

0.2

Collectively, the results described above indicate that ATR phosphorylates ETV1 and stabilizes it from proteolytic degradation.

SIGNOR-279355

P12931

Q06124

0

dephosphorylation

up-regulates activity

0.653

Several protein tyrosine phosphatases are capable of activating Src by dephosphorylating Y530 (reviewed in ref. 9). These include PTP-α, PTP-λ, SHP-1, SHP-2, and PTP1B

SIGNOR-248671

Q16873

P23443

0

phosphorylation

down-regulates activity

0.2

Here, we identified Ser(36) as the major p70S6k phosphorylation site, along with a low frequency site at Thr(40), using an in vitro phosphorylation assay combined with mass spectrometry. Cellular LTC4S activity is suppressed by PKC-mediated phosphorylation, and recently a downstream p70S6k was shown to play an important role in this process.

SIGNOR-277256

P10275

Q9NQU5

0

phosphorylation

down-regulates quantity by destabilization

0.2

Furthermore, AR phosphorylation at Ser-578 by PAK6 promotes AR-E3 ligase murine double minute-2 (Mdm2) association, causing AR degradation upon androgen stimuli.

SIGNOR-279247

P45984

P54259

1

phosphorylation

down-regulates activity

0.2

Dentatorubral-pallidoluysian atrophy protein is phosphorylated by c-jun nh2-terminal kinase. serine 734 of the drpla protein is a phospho-acceptor site by jnk. The phosphorylation may be coupled to the activation of a protease. The molecular size of drpla protein detected in the rat brain with the specific phosphopeptide antibody was 150_kda, which was slightly smaller than that expected from the sequence and the results with the human protein. The phosphorylated forms of ha-tagged human drpla gradually disappeared after osmotic treatment,

SIGNOR-102402

P23528

P53671

0

phosphorylation

down-regulates activity

0.766

We report here that limk1 and limk2 phosphorylate both cofilin and actin-depolymerizing factor (adf) specifically at ser-3 and exhibit partially distinct substrate specificity when tested using site-directed cofilin mutants as substrates

SIGNOR-105098

O96017

Q13263

1

phosphorylation

down-regulates activity

0.411

In particular, Chk2 phosphorylates KAP1 on Ser473 decreasing the interaction between KAP1 and HP1 proteins: this post translational modification promotes HP1\u03b2 mobilization and the reorganization of chromatin structure favoring the repair of DNA breaks inside heterochromatin [ , ].|Of note, phosphorylation of S473 by Chk2 decreases the interaction between KAP1 and HP1 proteins and is necessary for HP1\u03b2 mobilization, a key event for DNA repair in the heterochromatin [ - ].

SIGNOR-279730

Q92918

P00519

0

phosphorylation

up-regulates activity

0.379

C-Abl phosphorylates HPK1 in cytoplasm and stimulates HPK1 activity. the c-Abl phosphorylation site (YXXP) in HPK1 (Y232QPP; aa 232–235) is localized in HPK1-KD

SIGNOR-251429

P02818

P15036

0

transcriptional regulation

up-regulates quantity by expression

0.2

Ets2 is expressed at high levels during the differentiation and matrix mineralization phases of MC3T3-E1 culture. In addition, several extracellular matrix (ECM) associated gene products are targets of Ets2. Some of these matrix associated genes include: bone sialoprotein, osteonectin, osteocalcin and osteopontin

SIGNOR-259875

Q9UNE7

Q9BXL7

1

ubiquitination

up-regulates activity

0.327

Subsequently, the ubiquitination of CARMA1 catalyzed by STUB1 was identified as Lys 27 linked, which is important for CARMA1 mediated NF-kappaB activation.

SIGNOR-278720

Q02535

Q14289

0

phosphorylation

up-regulates quantity

0.2

Taken together these findings demonstrated that Pyk2 mediates the expression of ID3 protein.|Together these findings from the combined MS+MS/MS data confirm that Flag tagged ID3 is phosphorylated by active recombinant Pyk2 kinase; and support the phospho-Tyr band that was detected at the corresponding MW ~ 13 kDA for Flag-ID3 by immunoblot.

SIGNOR-278496

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

P19429

P17612

0

phosphorylation

up-regulates activity

0.423

Phosphorylation at ser 23/24 (e.g., by pka or pkg) results in reduction in myofilament ca2+ sensitivity and an increase in crossbridge cycling rate, leading to acceleration of relaxation and an increase in power output but a reduced economy of contraction. Conversely, phosphorylation at ser 43/45 (by pkc) is associated with reduced maximum ca2+-activated force and decreased crossbridge cycling rates, which are likely to reduce power output and delay relaxation, with an increased economy of contraction.

SIGNOR-134605

P04183

P24941

0

phosphorylation

down-regulates

0.296

Given that the dimeric form of tk1 is less active than the tetrameric, we propose that mitotic phosphorylation of serine-13 is of physiological importance, in that it may counteract atp-dependent activation of tk1 by affecting its quaternary structure, thus attenuating its enzymatic function at the g2/m phase.

SIGNOR-95578

Q9BZS1

P26358

0

transcriptional regulation

down-regulates quantity by repression

0.488

Our results showed that arsenic induced the high expression of DNMT1 and Foxp3 gene promoter methylation level, thereby inhibiting the expression levels of Foxp3, followed by decreasing Tregs and reducing related anti-inflammatory cytokines, such as interleukin 10 (IL-10) and interleukin 10 (IL-35)

SIGNOR-269053

P01106

Q13485

0

transcriptional regulation

down-regulates quantity by repression

0.64

Down-regulation of c-Myc is a critical event for growth inhibition induced by transforming growth factor-β (TGF-β) and is frequently impaired in cancer cells. We determined a Smad-responsive element in the c-mycpromoter.

SIGNOR-251493

P49810

Q14790

0

cleavage

up-regulates activity

0.332

In decreasing order of activity, caspase-8, -3, -1, -6 and -7 proteolysed PS2 at the recognition site D326SYD329.

SIGNOR-261752

Q7Z6B7

P63000

1

gtpase-activating protein

down-regulates activity

0.56

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-260515

P04001

Q92753

0

transcriptional regulation

up-regulates quantity by expression

0.2

These observations indicate that RORβ is required for the induction of S opsin and support the conclusion that RORβ regulates Opn1sw transcription in a direct manner through ROREs within its proximal promoter region. In addition, they explain the greatly diminished expression of Opn1sw observed in the retina of RORβ-/- mice.

SIGNOR-266851

P42345

Q96EB6

1

phosphorylation

down-regulates activity

0.551

These results demonstrate that the inhibition of SIRT1 by mTOR fosters survival of DNA damage-induced prematurely senescent squamous cell carcinoma cells via Bfl-1/A1 in the absence of functional p53.|This process involved the mTOR-dependent phosphorylation of SIRT1 at serine 47, resulting in the inhibition of the deacetylase activity of SIRT1.

SIGNOR-280047