GleghornLab/Signor_2class · Datasets at Hugging Face

IdA string	IdB string	labels int64	mechanism string	effect string	score float64	sentence string	signor_id string
P17542	Q99816	1	polyubiquitination	down-regulates quantity by destabilization	0.2	These data suggest that Tal mediates polyubiquitylation of the lysine residues in the VPS28-binding region of TSG101, leading to subsequent degradation of TSG101.	SIGNOR-271636
P22681	Q04759	0	phosphorylation	up-regulates activity	0.355	PKC-θ-mediated phosphorylation of serine and tyrosine residues of c-Cbl prevents its inhibitory effect. Phosphorylation of c-Cbl by PKC-θ inhibits the recruitment of Sh2-containing proteins and subsequent association of cbl E3 ubiquitin ligase with its target proteins	SIGNOR-274144
P55212	P02545	1	cleavage	down-regulates	0.662	Lamin a breakdown is largely mediated by caspase-6 during the execution phase of apoptosis.	SIGNOR-83611
Q9BPZ7	P31749	0	phosphorylation	up-regulates activity	0.703	Akt phosphorylates SIN1 at T86, enhancing mTORC2 kinase activity, which leads to phosphorylation of Akt S473 by mTORC2, thereby catalyzing full activation of Akt.	SIGNOR-276932
P04234	P06239	0	phosphorylation	up-regulates activity	0.571	Last, we demonstrate directly that members of the CD3 complex, including the gamma, delta, and epsilon chains, as well as a putative zeta subunit, can be phosphorylated at tyrosine residues by the CD4/CD8.p56lck complex.	SIGNOR-259929
P17509	P69891	1	transcriptional regulation	down-regulates quantity by repression	0.2	HOXB6 protein represses globin transcript levels in stably transfected K562 cells in a DNA-binding dependent fashion.	SIGNOR-261638
P27348	P68400	0	phosphorylation	down-regulates activity	0.347	The neuroprotective effect of 14-3-3theta against rotenone toxicity is dependent on the inhibition of the pro-apoptotic factor Bax\|Phosphorylation at S232 induced by rotenone is reduced by casein kinase inhibitors, and is not dependent on alphasyn.\| The S232D mutant partially reduced the ability of 14-3-3theta to inhibit Bax activation in response to rotenone. Based on these findings, we propose that phosphorylation of 14-3-3s at serine 232 contributes to the neurodegenerative process in PD.	SIGNOR-264405
P24394	P35568	1	phosphorylation	up-regulates	0.566	Irs-1 and a homologous protein, irs-2 (also known as 4-phosphotyrosine substrate), are recruited to phosphorylated y497 of IL-4R After ligand binding, leading to phosphorylation and activation of irs-1 and irs-2.	SIGNOR-100768
P51451	P12318	1	phosphorylation	up-regulates activity	0.436	To identify the FcgammaRII-phosphorylating protein tyrosine kinase (PTK), we used the combination of an in vitro and an in vivo approach. In an in vitro assay using recombinant cytoplasmic tails of the different FcgammaRII isoforms as well as tyrosine exchange mutants, we show that each of the BCR-associated PTKs (Lyn, Blk, Fyn, and Syk) shows different phosphorylation patterns with regard to the different FcgammaR isoforms and point\|Fyn and Blk definitely phosphorylate Y-282 in the ITAM of Fc_RIIa/c, whereas the non-ITAM tyrosine residue (Y-275) becomes phosphorylated by Syk, as the phosphorylation of double point mutants shows. In addi-tion to these tyrosine residues, Fyn, Blk, and Syk might phosphorylate the most C-terminal tyrosine residue (Y-298) because altering this tyrosine residue together with one of the tyrosine residues clearly shown to be phosphorylated by the respective PTK results in the abrogation of phosphorylation.	SIGNOR-249312
Q15208	Q9Y2U5	0	phosphorylation	up-regulates quantity by stabilization	0.402	Our data suggest that Ser91 phosphorylation of STK38 by MEKK2 possibly blocks the interaction of calpain with STK38 or disrupts proper conformation for cleaving, thereby protecting STK38 from calpain-dependent degradation.	SIGNOR-279066
P41240	P17612	0	phosphorylation	up-regulates activity	0.338	Activation of the cooh-terminal src kinase (csk) by camp-dependent protein kinase inhibits signaling through the t cell receptor.Pka phosphorylates csk at s364 in vitro and in vivo leading to a two- to fourfold increase in csk activity that is necessary for camp-mediated inhibition of tcr-induced interleukin 2 secretion.	SIGNOR-105229
P29375	P60484	1	transcriptional regulation	down-regulates quantity by destabilization	0.289	The retinoblastoma binding protein 2 (RBP2) belongs to the KDM5 family, and is also known as JARID1A or KDM5A. We found that histone H3 lysine 4 (H3K4) demethylase RBP2 expression is negatively correlated with BCR-ABL expression, which suggests a regulatory link between these two genes. We also discovered that RBP2 mediates the dephosphorylation of BCR-ABL by directly downregulating PTEN expression, depending on histone demethylase activity, while PTEN targets protein phosphatase activity of BCR-ABL, a phosphatase which directly dephosphorylates BCR-ABL.	SIGNOR-260079
Q8IW41	Q9UKI8	0	phosphorylation	up-regulates activity	0.2	We established that TLK1 phosphorylates MK5 on three residues (S160, S354 and S386), resulting in MK5 activation, and additionally, mobility shifts of MK5 also supported its phosphorylation by TLK1 in transfected HEK 293 cells.	SIGNOR-276747
Q13237	Q01970	1	phosphorylation	down-regulates activity	0.525	PKG can directly phosphorylate PLC-beta2 and PLC-beta3 in vitro with purified proteins and in vivo with metabolic labeling. Phosphorylation of PLC-beta leads to the inhibition of G-protein-activated PLC-beta3 activity by 50-70% in COS-7 cell transfection assays. By using phosphopeptide mapping and site-directed mutagenesis, we further identified two key phosphorylation sites for the regulation of PLC-beta3 by PKG (Ser(26) and Ser(1105)). Mutation at these two sites (S26A and S1105A) of PLC-beta3 completely blocked the phosphorylation of PLC-beta3 protein catalyzed by PKG.	SIGNOR-249078
Q8TDX7	P52732	1	phosphorylation	up-regulates activity	0.407	NEK7 regulates these processes in part through phosphorylation of the kinesin Eg5/KIF11, promoting its accumulation on microtubules in distal dendrites.	SIGNOR-273890
O60260	Q07812	1	ubiquitination	down-regulates quantity by destabilization	0.2	The E3 ligase parkin, which is known to trigger mitochondria specific autophagy, ubiquitylates BAX K128 and targets the pro apoptotic BCL-2 protein for proteasomal degradation.	SIGNOR-278529
P07288	Q96ST3	0	transcriptional regulation	down-regulates quantity by repression	0.2	Chromatin immunoprecipitation (ChIP) and DNA affinity precipitation analysis demonstrated that Ebp1 and Sin3A associate at the PSA and E2F1 promoters. Functionally, Sin3A enhanced the ability of Ebp1 to repress transcription of androgen receptor (AR) and E2F1 regulated genes.	SIGNOR-253663
Q9GZQ8	P19484	0	transcriptional regulation	up-regulates quantity by expression	0.391	As expected, we found that glucose deprivation induced the binding of TFEB (Figure S4C) and ACSS2 (Figure S4D) to the promoter regions of MAP1LC3B, ATG3, and WIPI-1 as well as mRNA (Figure 3H) and protein (Figure 3I) expression of these genes;	SIGNOR-276559
P17252	P47712	1	phosphorylation	up-regulates	0.564	Pkcalfa, but not pkcbeta, is the predominant cpkc isoenzyme required for cpla2 protein phosphorylation and maximal induction of cpla2 enzymatic activity.	SIGNOR-149406
O95235	Q15173	0	dephosphorylation	up-regulates activity	0.2	We identify MKlp2 as an essential protein for promoting abscission, which may regulate tethering and stabilizing of the PM to the microtubule cytoskeleton. Aurora B phosphorylation of MKlp2 S878 in the LAM is a key inhibitory signal for abscission. Conversely, B56-PP2A promotes abscission by opposing Aurora B phosphorylation of MKlp2 S878.	SIGNOR-262660
P18669	Q16512	0	phosphorylation	down-regulates	0.254	Activated pak1 inhibits glycolysis by association of its catalytic domain with pgam-b and subsequent phosphorylation of the enzyme on serine residues 23 and 118, thereby abolishing pgam activity.	SIGNOR-91602
P31749	Q9BWT1	1	phosphorylation	down-regulates	0.338	The prosurvival kinase akt phosphorylates cdca7 at threonine 163, promoting binding to 14-3-3, dissociation from myc, and sequestration to the cytoplasm. we have mapped the domains of interaction and have discovered that akt phosphorylates cdca7 near this contact region, leading to loss of its association with myc, binding to 14-3-3 proteins, and exclusion from the nucleus.	SIGNOR-252533
Q16825	P12931	1	dephosphorylation	up-regulates	0.643	Ptpd1 activates src tyrosine kinase and increases the magnitude and duration of epidermal growth factor (egf) signaling.	SIGNOR-124774
P69905	P15289	0	acetylation	up-regulates activity	0.2	ASA acetylates hemoglobin. Purified acetylated hemoglobin had a slightly increased oxygen affinity and decreased heme-heme interaction.	SIGNOR-251773
Q15910	Q13315	0	phosphorylation	down-regulates quantity	0.458	Enhancer of zeste homolog 2 (EZH2), a core catalytic component of polycomb repressive complex 2, is a new ATM kinase target, and ATM-mediated phosphorylation of EZH2 on Ser734 reduces protein stability.\|We verified that S734 is the predominant ATM site on EZH2 by performing ATM in vitro kinase assays using GST-EZH2 fusion proteins as substrates (Fig. 2b). The phosphorylation signal was nearly lost when the EZH2-S734A mutant was used as substrate	SIGNOR-279586
Q05086	O60936	1	ubiquitination	down-regulates quantity by destabilization	0.2	Incubation of transfected HEK293T cells with the proteasome inhibitor, MG132 blocked Ube3A mediated degradation of Arc suggesting that Ube3A degrades Arc via the ubiquitin proteasome system .\|The ubiquitination of Arc by Ube3A was confirmed by mass spectrometry which revealed that Ube3A catalyzed the polyubiquitination of Arc on Lysine 268 and 269 ( xref ).	SIGNOR-278522
P98172	Q12923	0	dephosphorylation	up-regulates activity	0.708	Loss of PTPN13 function increases EFNB1 phosphorylation, enhances EFNB1 's interaction with ERBB1 and correlates with potentiated ERK1/2 activation.\|Moreover, acquisition of PTPN13 loss-of-function mutations or its decreased expression (due to HPV infection or epigenetic silencing) may further enhance ERBB1 and EFNB1 mediated signals.	SIGNOR-277002
O15054	P68431	1	demethylation	down-regulates activity	0.2	Ubiquitously Transcribed Tetratricopeptide Repeat on chromosome X (UTX) and Jumonji D3 (JMJD3) as novel histone demethylases that catalyze the removal of di- and trimethyl groups on histone H3 lysine 27, thereby promoting target gene activation.	SIGNOR-260018
P24941	P30305	0	dephosphorylation	up-regulates activity	0.767	CDC25B is also able to dephosphorylate and activate CDK2-Cyclin A and CDK2-Cyclin E complexes [ xref \u2013 xref ].	SIGNOR-277140
P31751	Q99683	1	phosphorylation	down-regulates activity	0.646	Akt2 interacts with and phosphorylates ask1 at ser-83 resulting in inhibition of its kinase activity	SIGNOR-100588
P19784	Q99250	1	phosphorylation	up-regulates activity	0.2	We found that the ankyrin-binding motif of Na(v)1.2 that determines channel concentration at the AIS depends on a glutamate residue (E1111), but also on several serine residues (S1112, S1124, and S1126). We showed that phosphorylation of these residues by protein kinase CK2 (CK2) regulates Na(v) channel interaction with ankyrins. \| inhibition of CK2 activity reduced sodium channel accumulation at the AIS of neurons. In conclusion, CK2 contributes to sodium channel organization by regulating their interaction with ankyrin G.	SIGNOR-275758
P61586	Q7Z628	0	guanine nucleotide exchange factor	up-regulates activity	0.832	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-260561
Q13315	Q9HA47	1	phosphorylation	down-regulates quantity by destabilization	0.2	ATM also phosphorylates UCK1 at S145, significantly enhancing the KLHL2-UCK1 complex formation\|We demonstrated that the ubiquitin E3 ligase KLHL2 interacted with UCK1 and mediated its polyubiquitination at the K81 residue and degradation.	SIGNOR-275963
Q9UBE8	P46531	1	phosphorylation	down-regulates	0.382	Nlk-phosphorylated notch1icd is impaired in its ability to form a transcriptionally_ active_ ternary_ complex.	SIGNOR-163697
Q9P1W9	O95644	1	phosphorylation	up-regulates activity	0.261	In addition to PIM1, also PIM2 and PIM3 were able to phosphorylate WT, but not MM NFATC1 in vitro (Fig. (Fig.22c).	SIGNOR-276772
Q9BV73	Q9H0K1	0	phosphorylation	down-regulates	0.321	Here, we show that the salt inducible kinase 2 (sik2) localizes at the centrosome, plays a key role in the initiation of mitosis, and regulates the localization of the centrosome linker protein, c-nap1, through s2392 phosphorylation	SIGNOR-167488
Q05397	P06213	0	phosphorylation	up-regulates activity	0.353	P125(Fak) sequence comprising amino acids 568-582, which contains tyrosines 576 and 577 of the kinase domain regulatory loop, is phosphorylated by the insulin receptor. p125(Fak) phosphorylation by the receptor results in its activation.	SIGNOR-251323
Q13547	P49715	1	transcriptional regulation	down-regulates	0.436	These data suggest that c/ebp beta activates a single unified pathway of adipogenesis involving its stimulation of ppargamma expression, which then activates c/ebp alpha expression by dislodging hdac1 from the promoter for degradation in the proteasome	SIGNOR-210013
P06239	P41240	0	phosphorylation	down-regulates	0.538	P50csk tyrosine kinase phosphorylates p56lck at tyr-505 and down regulates its catalytic activity.	SIGNOR-20371
Q13224	P60484	0	dephosphorylation	down-regulates activity	0.296	GluN2B Y1472 site is dephosphorylated by PTEN .	SIGNOR-277165
O60566	P25054	1	phosphorylation	up-regulates activity	0.428	These findings support a model in which BubR1 kinase may directly regulate APC function involved in stable kinetochore microtubule attachment.\|Using purified components, BubR1 directly phosphorylates APC and forms a ternary complex with APC and microtubules.	SIGNOR-279393
P00533	Q9ULU4	0	transcriptional regulation	down-regulates quantity by repression	0.2	Our quantitative ChIP experiments confirmed that ZMYND8 and JARID1D were co-localized at Slug, CD44, VEGFA, and EGFR genes (Figures 4F–4I). Our ChIP results also showed that ZMYND8 repressed and occupied other JARID1D target genes, such as the matrix metalloproteinase 1 (MMP1) and MMP3, that we previously reported	SIGNOR-262040
Q86YT6	Q00535	0	phosphorylation	up-regulates activity	0.325	Similar to the mechanism of PAR-1 regulation of Mib in neurogenesis, CDK5 phosphorylation is proposed to enhance Mib1 ligase activity leading to destabilization.\|The cyclin dependent kinase 5 (CDK5) enriched in neurons phosphorylates Mib1 and suppresses the inhibitory effects of Mib1 on neurite morphology.	SIGNOR-280217
Q9UQL6	P17612	0	phosphorylation	up-regulates activity	0.2	PKA/Cdk5-mediated phosphorylation of HDAC5 at Ser279 within the NLS promotes nuclear localization of HDAC5 and interaction with the nuclear corepressor complex	SIGNOR-198658
Q9NPI1	Q13315	0	phosphorylation	down-regulates activity	0.2	ATM Directly Phosphorylates BRD7 at Ser 263 Site.	SIGNOR-279780
P31751	Q96B36	1	phosphorylation	down-regulates	0.674	Insulin-stimulated phosphorylation of pras40 by akt/pkb suppresses its mtorc1 inhibitory activity.	SIGNOR-153931
P68400	Q6VY07	1	phosphorylation	up-regulates activity	0.545	Phosphorylation of Ser278 by CK2 or a Ser278-->Asp mutation increased the interaction between PACS-1 and cargo, whereas a Ser278-->Ala substitution decreased this interaction. Moreover, the Ser278-->Ala mutation yields a dominant-negative PACS-1 molecule that selectively blocks retrieval of PACS-1-regulated cargo molecules to the TGN.	SIGNOR-250925
P53350	Q2NKX8	1	relocalization	up-regulates	0.88	Human pich was identified as an interaction partner and substrate of plk1. Our data indicate that plk1 prevents the association of pich with chromosome arms and restricts its localization to the kt/centromere region	SIGNOR-152136
P06241	P15498	1	phosphorylation	up-regulates	0.636	Study of t cells from a fyn-deficient tcr transgenic mouse also showed that fyn was required for tyrosine phosphorylation and activation of vav induced by both antagonist and agonist peptides.	SIGNOR-82287
Q92585	P68431	1	acetylation	down-regulates activity	0.2	The n-terminal domain of maml1 directly interacts with both p300 and histones, and the p300-maml1 complex specifically acetylates histone h3 and h4 tails in chromatin.	SIGNOR-153038
P61586	Q9NRY4	0	gtpase-activating protein	down-regulates activity	0.893	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-260492
P01106	P52789	1	transcriptional regulation	up-regulates quantity	0.37	Here, using the P493-6 Burkitt's lymphoma model with an inducible MYC, we demonstrate that HIF-1 cooperates with dysregulated c-Myc to promote glycolysis by induction of hexokinase 2, which catalyzes the first step of glycolysis, and pyruvate dehydrogenase kinase 1, which inactivates pyruvate dehydrogenase and diminishes mitochondrial respiration.	SIGNOR-259986
Q9ULU4	P16070	1	transcriptional regulation	down-regulates quantity by repression	0.2	Our quantitative ChIP experiments confirmed that ZMYND8 and JARID1D were co-localized at Slug, CD44, VEGFA, and EGFR genes (Figures 4F–4I). Our ChIP results also showed that ZMYND8 repressed and occupied other JARID1D target genes, such as the matrix metalloproteinase 1 (MMP1) and MMP3, that we previously reported	SIGNOR-262039
Q96PH1	P17252	0	phosphorylation	up-regulates	0.2	A constitutively active form of pkc? Robustly increased basal and pma-stimulated nox5 activity and promoted the phosphorylation of nox5 on ser490, thr494, and ser498.	SIGNOR-204550
P53350	Q00987	1	phosphorylation	up-regulates	0.465	Here we show that the oncogenic and cell cycle-regulatory protein kinase, polo-like kinase-1 (plk1), phosphorylates mdm2 at one of these residues, ser260, and stimulates mdm2-mediated turnover of p53. These data are consistent with the idea that deregulation of plk1 during tumourigenesis may help suppress p53 function.	SIGNOR-94272
Q6JBY9	Q16644	0	phosphorylation	down-regulates activity	0.482	Human CapZIP was phosphorylated at Ser-179 and Ser-244 by MAPKAP-K2 (mitogen-activated protein kinase-activated protein kinase 2) or MAPKAP-K3 in vitro. In the present paper we have identified CapZIP as a protein that is phosphorylated exceptionally rapidly by several SAPKs in vitro (Figure 4), and which is expressed in muscles and immune cells. Both MAPKAP-K2 and MAPKAP-K3 phosphorylated CapZIP at Ser-179 in vitro. An important clue to the function of CapZIP and its phosphorylation came from the finding that it binds to the actin-capping protein CapZ (Figure 7A), and that cellular stresses trigger the dissociation of these two proteins (Figure 7B).Such an effect is presumably lost when CapZIP is phosphorylated and dissociates from CapZ.	SIGNOR-263082
Q8TAQ5	Q13315	0	phosphorylation	down-regulates activity	0.459	These results indicate that Apak is a genuine substrate of ATM kinase. Apak phosphorylation on Ser 68 is critical for p53-mediated apoptosis. in response to DNA damage, ATM is rapidly activated by autophosphorylation and mediates p53 activation through disruption of the Apak–p53 complex by phosphorylating Apak on Ser 68.	SIGNOR-273513
P56178	P10451	1	transcriptional regulation	up-regulates quantity	0.373	Dlx5 initiates a complete osteogenic differentiation in these early primary cells, by triggering Runx2, osteopontin, alkaline phosphatase, and other gene expression according to the sequential temporal sequence observed during skull osteogenesis in vivo.	SIGNOR-245340
P45984	P45985	0	phosphorylation	up-regulates	0.729	Mkk4, which activates p38gamma, p38delta, and jnk2 to phosphorylate p53 on ser-33 and cause a transient g(1) arrest. A map kinase kinase kinase (mapkkk), termed ask1, was identified that activated two different subs of map kinase kinases (mapkk), sek1 (or mkk4) and mkk3/mapkk6 (or mkk6), which in turn activated stress-activated protein kinase (sapk, also known as jnk;c-jun amino-terminal kinase) here we report that mkk4 shows a striking preference for the tyrosine residue (tyr-185), and mkk7 a striking preference for the threonine residue (thr-183) in three sapk1/jnk1 isoforms tested (jnk1 alpha 1, jnk2 alpha 2 and jnk3 alpha 1)	SIGNOR-197998
P12931	Q96J92	1	phosphorylation	down-regulates activity	0.2	Using Western blot and mass spectrometry, we now identify three sites in WNK4 that are phosphorylated by c-Src: Tyr(1092), Tyr(1094), and Tyr(1143), and show that both c-Src and protein tyrosine phosphatase type 1D (PTP-1D) coimmunoprecipitate with WNK4.	SIGNOR-276897
O94782	P06493	0	phosphorylation	up-regulates activity	0.371	In this study, we show that Ser313 phosphorylation in USP1 is required for its interaction with UAF1 and for the stimulation of USP1's activity. We further demonstrated that CDK1 is responsible for Ser313 phosphorylation, and protein phosphatase treatment of USP1 can lead to inactivation of USP1/UAF1.	SIGNOR-276423
P68431	P11309	0	phosphorylation	down-regulates activity	0.2	Pim1-dependent phosphorylation of histone h3 at serine 10 is required for myc-dependent transcriptional activation and oncogenic transformation.	SIGNOR-156946
P04637	P45983	0	phosphorylation	up-regulates	0.796	Activated jnk phosphorylates p53	SIGNOR-59812
P24844	P17252	0	phosphorylation	down-regulates	0.278	Rlc can also be phosphorylated at ser1/ser2/thr9 by protein kinase c (pkc). Biophysical studies show that phosphorylation at these sites leads to an increase in the km of myosin light chain kinase (mlck) for rlc, thereby indirectly inhibiting myosin ii activity	SIGNOR-192792
Q00535	P35222	1	phosphorylation	up-regulates activity	0.371	By combining multiple network relations with PTM proteoform specific functional information, we proposed a mechanism to explain the observation that the cyclin dependent kinase CDK5 positively regulates beta-catenin co-activator activity.\|CDK5 phosphorylates beta-catenin on Ser 191 and Ser 246 (PR :000037229)	SIGNOR-279516
Q96JH7	P06493	0	phosphorylation	down-regulates activity	0.537	We clarified that VCIP135, an essential factor in both p97 membrane fusion pathways, is phosphorylated on Threonine-760 and Serine-767 by Cdc2 at mitosis and that this phosphorylated VCIP135 does not bind to p97.	SIGNOR-265038
P67775	Q8TD08	1	dephosphorylation	down-regulates	0.289	Erk8 (extracellular-signal-regulated protein kinase 8) expressed in escherichia coli or insect cells was catalytically active and phosphorylated at both residues of the thr-glu-tyr motif. Dephosphorylation of the threonine residue by pp2a (protein serine/threonine phosphatase 2a) decreased erk8 activity by over 95% in vitro, whereas complete dephosphorylation of the tyrosine residue by ptp1b (protein tyrosine phosphatase 1b) decreased activity by only 15-20%	SIGNOR-142977
P56545	Q9UNE7	0	ubiquitination	down-regulates quantity by destabilization	0.331	Our data showed that CHIP depletion resulted in up-regulation of the steady-state level of CtBP2 ( Fig. 1 B) and that CHIP ubiquitinated CtBP2 for proteasomal degradation ( Fig. 3 A).	SIGNOR-278722
P05771	P49768	1	phosphorylation	up-regulates activity	0.2	A phosphorylation site at serine residue 346 was identified that is selectively phosphorylated by PKC but not by PKA. This site is localized within a recognition motif for caspases, and phosphorylation strongly inhibits proteolytic processing of PS1 by caspase activity during apoptosis.	SIGNOR-249237
P17096	Q03135	0	relocalization	up-regulates activity	0.265	CAV1 was shown to stimulate GLUT3 transcription via an HMGA1-binding site within the GLUT3 promoter. HMGA1 was found to interact with and activate the GLUT3 promoter and CAV1 increased the HMGA1 activity by enhancing its nuclear localization.	SIGNOR-254428
Q9Y2K6	O95714	0	ubiquitination	down-regulates quantity	0.372	HERC2 promotes USP20 degradation.\|Under unperturbed condition, HERC2 ubiquitinates USP20 and promotes ubiquitination mediated proteasomal degradation of USP20, regulating the status of K48 linked polyubiquitination of CLASPIN and ensuring appropriate protein levels of CLASPIN during the S-phase.	SIGNOR-278692
P35790	Q13535	0	phosphorylation	up-regulates activity	0.248	In particular, ATR phosphorylates Chk 1 and ATM signals to Chk 2.	SIGNOR-280184
P52333	P17706	0	dephosphorylation	down-regulates activity	0.697	Upon ligand binding, IL-2R , IL-6R or LeptinR , IFN-_R , IFN-_R and PRLR or growth hormone (GH) receptor associated JAKs become activated. These JAKs mediate phosphorylation of specific tyrosine residues and recruit STATs. Activated STATs are released from the receptor and translocate to the nucleus. PTP1B dephosphorylates JAK2, TYK2 and STAT5 . The 45-kDa form of TC-PTP was shown to dephosphorylate JAK1 and JAK3 as well as STAT1, STAT3 and STAT5.	SIGNOR-133078
P31749	P08670	1	phosphorylation	up-regulates quantity by stabilization	0.647	The binding of akt (tail region) to vim (head region) results in vim ser39 phosphorylation enhancing the ability of vim to induce motility and invasion while protecting vim from caspase-induced proteolysis.	SIGNOR-252511
Q13153	P41182	1	phosphorylation	down-regulates activity	0.2	The transcriptional repressor B-cell lymphoma (BCL)-6 downregulates genes involved in cell-cycle progression and becomes inactivated following phosphorylation by the Rac1 GTPase-activated protein kinase PAK1.	SIGNOR-253930
P45452	P02458	1	cleavage	down-regulates quantity by destabilization	0.544	Although it appears that MMP-1 and MMP-13 both cleave type II collagen initially at the same site, MMP-13 affects a secondary cleavage to produce a 1/4-size collagen fragment with an NH2 terminus three amino acids removed from the primary cleavage site.The present work has demonstrated expression of MMP-13 in human osteoarthritic cartilage and shown that MMP-13 has significant type II collagen degrading activity.	SIGNOR-256340
P31749	P49841	1	phosphorylation	down-regulates activity	0.792	Active AKT, a common mediator of cell survival signals induced by radiation through multiple intracellular signaling pathways,11, 12 suppresses apoptosis. AKT positively regulates cyclin D1 expression through inactivation of glycogen synthase kinase 3beta (GSK3B). The AKT-mediated phosphorylation of glycogen synthase kinase 3b on serine9 decreases its kinase activity for Thr286 of cyclin D1, which inhibits the nuclear export and the cytoplasmic proteasomal degradation of cyclin D1	SIGNOR-245416
Q13188	Q9UL54	0	phosphorylation	up-regulates	0.274	In addition, the thousand-and-one (tao) amino acids kinase or taok13 has been shown to directly phosphorylate and activate hpo or mst1/2.	SIGNOR-201327
P33981	P00519	1	phosphorylation	down-regulates	0.279	Ttk phosphorylation of thr735 was associated with partial inhibition of nuclear targeting of c-abl.	SIGNOR-181064
P00533	P27361	0	phosphorylation	down-regulates	0.557	It is likely that the map2 and ert kinases account for the phosphorylation of the egf receptor at thr669 (egf receptor (krel veplt669psgeapnqallr)) observed in cultured cells.Phosphorylation at ser-695 is partial and occurs only if thr-693 is phosphorylated. Phosphorylation at thr-678 and thr-693 by prkd1 inhibits egf-induced mapk8/jnk1 activation.	SIGNOR-20549
P18206	P12931	0	phosphorylation	down-regulates activity	0.76	The phosphorylation of vinculin on tyrosine residues 100 and 1065, mediated by SRC kinases, affects cell spreadingWhen phosphorylated, the vinculin tail exhibited significantly less binding to the vinculin head domain than the unphosphorylated tail.	SIGNOR-247424
Q15375	P56915	0	transcriptional regulation	down-regulates quantity by repression	0.2	We demonstrate that Goosecoid can act as a repressor of its own promoter activity in transient co-transfection experiments in mouse P19 cells and in Xenopus embryos. Autorepression depends on the presence of the homeodomain and is mediated through the prd element more proximal to the transcriptional start site.	SIGNOR-261613
Q08211	P35637	0	relocalization	down-regulates activity	0.482	We found that ALS mutants of FUS co-localized with Caprin-1, DDX3X, and DHX9 in cytoplasmic inclusions that could lead to the mis-regulation of their respective pathways, providing further clues to the mechanism of ALS pathogenesis.\|FUS interacting proteins were sequestered into the cytoplasmic mutant FUS inclusions that could lead to their mis-regulation or loss of function, contributing to ALS pathogenesis. \| We also demonstrated the co-localization of DHX9, DDX3X and Caprin-1 with cytoplasmic EGFP-P525L mutant FUS inclusions in primary cortical neurons	SIGNOR-262810
Q8IV63	O75531	1	phosphorylation	down-regulates activity	0.491	Although VRK3 has been regarded as a genuine pseudokinase from structural and biochemical studies, recent reports suggest that VRK3 acts as an active kinase as well as a signaling scaffold in cells. Here, we demonstrate that VRK3 phosphorylates the nuclear envelope protein barrier-to-autointegration factor (BAF) on Ser4.\|Ectopic expression of VRK3 induces the translocation of BAF from the nucleus to the cytoplasm. I	SIGNOR-264564
P68400	P49427	1	phosphorylation	down-regulates activity	0.395	The ubiquitin-conjugating enzyme, cdc34, has been implicated in the ubiquitination of a number of vertebrate substrates, including p27(kip1), ikappabalpha, wee1, and myod. We show that mammalian cdc34 is a phosphoprotein that is phosphorylated in proliferating cells. Phosphorylation of cdc34 by the associated kinase maps predominantly to residues 203 and 222. Mutation of cdc34 at ck2-targeted residues, ser-203, ser-222, ser-231, thr-233, and ser-236, abolishes the phosphorylation of cdc34 observed in vivo and markedly shifts nuclearly localized cdc34 to the cytoplasm.	SIGNOR-110399
P01579	Q6NT76	0	transcriptional regulation	down-regulates quantity by repression	0.2	Additionally, by luciferase reporter assay, HMBOX1 displayed suppressive effect on the transcription activity of IFN-γ promoter.	SIGNOR-261625
P19784	P55087	1	phosphorylation	down-regulates activity	0.338	We found that the stress-induced kinase casein kinase (CK)II phosphorylates the Ser276 immediately preceding the tyrosine motif, increasing AQP4-mu 3A interaction and enhancing AQP4-lysosomal targeting and degradation. \| To determine whether Ser276 is an actual CKII substrate, we used GST–AQP4‐Cter proteins in which only one out of the three C‐terminal CKII consensus sites was sequentially conserved (Ser276, Ser285 and Ser315, respectively). Figure 7B (right panel) shows that the three serine residues, including Ser276, were indeed efficiently phosphorylated by CKII.	SIGNOR-250976
P68400	Q01892	1	phosphorylation	down-regulates	0.429	Serine residues 37 in the transactivation domain and 129, 144 and 146 in the pest domain of spi-b are phosphorylated by ckii in vitro. The ckii phosphorylation sites mapped in vitro are phosphorylated in vivo. Mutations of the ckii phosphorylation sites increase the ability of spi-b to transactivate. Spi-b phosphorylation by ckii reduces its stability	SIGNOR-73891
Q8IW41	Q12778	1	phosphorylation	up-regulates activity	0.422	The kinase MK5 phosphorylates and activates Foxo1 at serine 215, and this modification is required for Foxo1 to induce Rag transcription.	SIGNOR-280037
P04040	Q16236	0	transcriptional regulation	up-regulates quantity by expression	0.426	BTG2 was found to up-regulate expression of antioxidant enzymes known to be regulated by NFE2L2, including catalase, SOD1, and SOD2	SIGNOR-254651
Q15139	O94768	1	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
P00519	P32119	1	phosphorylation	down-regulates activity	0.284	Inactivation of peroxiredoxin I by phosphorylation allows localized H(2)O(2) accumulation for cell signaling. To determine whether Prxs are phosphorylated, we subjected recombinant human PrxI and II to an in vitro kinase assay with two nonreceptor PTKs, Lck and Abl, in the presence of [γ-32P]ATP. Both PTKs phosphorylated PrxI and PrxII. Phosphorylation of the wild-type protein was detected, whereas that of the Y194F mutant was not (Figure 1B), indicating that Tyr194 is the only site of tyrosine phosphorylation.	SIGNOR-276280
P68431	Q9C0A6	0	methylation	up-regulates activity	0.2	SETD5 Exhibits Intrinsic Methyltransferase Activity on H3K36. This assay showed that SETD5 has specific histone methyltransferase activity toward K36 but not for other residues such as K4 and K27 (Figure 8B). we revealed that SETD5 is endowed with H3K36 methyltransferase, which is necessary for RNA elongation and processing and, ultimately, correct gene transcription.	SIGNOR-264620
P04637	P68400	0	phosphorylation	up-regulates activity	0.668	Furthermore, we demonstrate that anisomycin- and tumor necrosis factor-alpha-induced phosphorylation of p53 at Ser-392, which is important for the transcriptional activity of this growth suppressor protein, requires p38 MAP kinase and CK2 activities.	SIGNOR-250967
P28482	P36956	1	phosphorylation	up-regulates	0.406	Map kinases erk1/2 phosphorylate sterol regulatory element-binding protein (srebp)-1a at serine 117 in vitro. mutation of serine 117 to alanine abolished erk2-mediated phosphorylation in vitro and the map kinase-related transcriptional activation of srebp-1a by insulin and platelet-derived growth factor in vivo.	SIGNOR-80092
P19474	Q13501	1	ubiquitination	down-regulates activity	0.404	TRIM21 directly ubiquitylates p62 at residue K7 to inhibit its oligomerization and sequestration function.\|TRIM21 negatively regulates p62 mediated sequestration of Keap1 and antioxidant response.	SIGNOR-278602
O00141	P46527	1	phosphorylation	down-regulates	0.469	Activated sgk1 and p27 phosphorylation at t157, and both were inhibited by short-term rapamycin treatment and by sgk1 shrna.	SIGNOR-179117
P06400	O96017	0	phosphorylation	up-regulates activity	0.423	Phosphorylation of prb at ser612 by chk1/2 leads to a complex between prb and e2f-1 after dna damageprb inhibits cell cycle progression through interactions with the e2f family of transcription factors. Here, we report that dna damage induced not only the dephosphorylation of prb at cdk phosphorylation sites and the binding of prb to e2f-1, but also the phosphorylation of prb at ser612. Phosphorylation of prb at ser612 enhanced the formation of a complex between prb and e2f-1	SIGNOR-153908
O95786	P68400	0	phosphorylation	down-regulates	0.2	Threonine at amino acid (aa) 770 and serine at aa 854 to 855 of rig-i are phosphorylated by casein kinase ii (ck2) in the resting state of the cell and dephosphorylated when cells are infected by rna virus. Mutation at aa position 770 or 854 to 855 of rig-i renders it constitutively active	SIGNOR-169404
Q12809	Q96PU5	0	ubiquitination	down-regulates quantity by destabilization	0.399	As quantified in Fig. 5 B, only Nedd4-2 significantly increased the basal ubiquitylation of hERG1, while Nedd4-2-C801S and the other ubiquitin ligases had no effect.\|The major findings of this study are as follows : 1) hERG1 interacts via its PY motif with the ubiquitin ligase Nedd4-2, 2) this interaction promotes the down-regulation of the functional form of the channel at the plasma membrane through Nedd4-2 ubiquitylation of the channel, and 3) I hERG1 is strongly decreased by Nedd4-2 catalytic dependent activity.The hERG1 PY motif is a highly conserved sequence across animal species lines, highlighting its crucial role in the regulation of the hERG1 channel at the cell surface.	SIGNOR-278771

P17542

Q99816

1

polyubiquitination

down-regulates quantity by destabilization

0.2

These data suggest that Tal mediates polyubiquitylation of the lysine residues in the VPS28-binding region of TSG101, leading to subsequent degradation of TSG101.

SIGNOR-271636

P22681

Q04759

0

phosphorylation

up-regulates activity

0.355

PKC-θ-mediated phosphorylation of serine and tyrosine residues of c-Cbl prevents its inhibitory effect. Phosphorylation of c-Cbl by PKC-θ inhibits the recruitment of Sh2-containing proteins and subsequent association of cbl E3 ubiquitin ligase with its target proteins

SIGNOR-274144

P55212

P02545

1

cleavage

down-regulates

0.662

Lamin a breakdown is largely mediated by caspase-6 during the execution phase of apoptosis.

SIGNOR-83611

Q9BPZ7

P31749

0

phosphorylation

up-regulates activity

0.703

Akt phosphorylates SIN1 at T86, enhancing mTORC2 kinase activity, which leads to phosphorylation of Akt S473 by mTORC2, thereby catalyzing full activation of Akt.

SIGNOR-276932

P04234

P06239

0

phosphorylation

up-regulates activity

0.571

Last, we demonstrate directly that members of the CD3 complex, including the gamma, delta, and epsilon chains, as well as a putative zeta subunit, can be phosphorylated at tyrosine residues by the CD4/CD8.p56lck complex.

SIGNOR-259929

P17509

P69891

1

transcriptional regulation

down-regulates quantity by repression

0.2

HOXB6 protein represses globin transcript levels in stably transfected K562 cells in a DNA-binding dependent fashion.

SIGNOR-261638

P27348

P68400

0

phosphorylation

down-regulates activity

0.347

The neuroprotective effect of 14-3-3theta against rotenone toxicity is dependent on the inhibition of the pro-apoptotic factor Bax|Phosphorylation at S232 induced by rotenone is reduced by casein kinase inhibitors, and is not dependent on alphasyn.| The S232D mutant partially reduced the ability of 14-3-3theta to inhibit Bax activation in response to rotenone. Based on these findings, we propose that phosphorylation of 14-3-3s at serine 232 contributes to the neurodegenerative process in PD.

SIGNOR-264405

P24394

P35568

1

phosphorylation

up-regulates

0.566

Irs-1 and a homologous protein, irs-2 (also known as 4-phosphotyrosine substrate), are recruited to phosphorylated y497 of IL-4R After ligand binding, leading to phosphorylation and activation of irs-1 and irs-2.

SIGNOR-100768

P51451

P12318

1

phosphorylation

up-regulates activity

0.436

To identify the FcgammaRII-phosphorylating protein tyrosine kinase (PTK), we used the combination of an in vitro and an in vivo approach. In an in vitro assay using recombinant cytoplasmic tails of the different FcgammaRII isoforms as well as tyrosine exchange mutants, we show that each of the BCR-associated PTKs (Lyn, Blk, Fyn, and Syk) shows different phosphorylation patterns with regard to the different FcgammaR isoforms and point|Fyn and Blk definitely phosphorylate Y-282 in the ITAM of Fc_RIIa/c, whereas the non-ITAM tyrosine residue (Y-275) becomes phosphorylated by Syk, as the phosphorylation of double point mutants shows. In addi-tion to these tyrosine residues, Fyn, Blk, and Syk might phosphorylate the most C-terminal tyrosine residue (Y-298) because altering this tyrosine residue together with one of the tyrosine residues clearly shown to be phosphorylated by the respective PTK results in the abrogation of phosphorylation.

SIGNOR-249312

Q15208

Q9Y2U5

0

phosphorylation

up-regulates quantity by stabilization

0.402

Our data suggest that Ser91 phosphorylation of STK38 by MEKK2 possibly blocks the interaction of calpain with STK38 or disrupts proper conformation for cleaving, thereby protecting STK38 from calpain-dependent degradation.

SIGNOR-279066

P41240

P17612

0

phosphorylation

up-regulates activity

0.338

Activation of the cooh-terminal src kinase (csk) by camp-dependent protein kinase inhibits signaling through the t cell receptor.Pka phosphorylates csk at s364 in vitro and in vivo leading to a two- to fourfold increase in csk activity that is necessary for camp-mediated inhibition of tcr-induced interleukin 2 secretion.

SIGNOR-105229

P29375

P60484

1

transcriptional regulation

down-regulates quantity by destabilization

0.289

The retinoblastoma binding protein 2 (RBP2) belongs to the KDM5 family, and is also known as JARID1A or KDM5A. We found that histone H3 lysine 4 (H3K4) demethylase RBP2 expression is negatively correlated with BCR-ABL expression, which suggests a regulatory link between these two genes. We also discovered that RBP2 mediates the dephosphorylation of BCR-ABL by directly downregulating PTEN expression, depending on histone demethylase activity, while PTEN targets protein phosphatase activity of BCR-ABL, a phosphatase which directly dephosphorylates BCR-ABL.

SIGNOR-260079

Q8IW41

Q9UKI8

0

phosphorylation

up-regulates activity

0.2

We established that TLK1 phosphorylates MK5 on three residues (S160, S354 and S386), resulting in MK5 activation, and additionally, mobility shifts of MK5 also supported its phosphorylation by TLK1 in transfected HEK 293 cells.

SIGNOR-276747

Q13237

Q01970

1

phosphorylation

down-regulates activity

0.525

PKG can directly phosphorylate PLC-beta2 and PLC-beta3 in vitro with purified proteins and in vivo with metabolic labeling. Phosphorylation of PLC-beta leads to the inhibition of G-protein-activated PLC-beta3 activity by 50-70% in COS-7 cell transfection assays. By using phosphopeptide mapping and site-directed mutagenesis, we further identified two key phosphorylation sites for the regulation of PLC-beta3 by PKG (Ser(26) and Ser(1105)). Mutation at these two sites (S26A and S1105A) of PLC-beta3 completely blocked the phosphorylation of PLC-beta3 protein catalyzed by PKG.

SIGNOR-249078

Q8TDX7

P52732

1

phosphorylation

up-regulates activity

0.407

NEK7 regulates these processes in part through phosphorylation of the kinesin Eg5/KIF11, promoting its accumulation on microtubules in distal dendrites.

SIGNOR-273890

O60260

Q07812

1

ubiquitination

down-regulates quantity by destabilization

0.2

The E3 ligase parkin, which is known to trigger mitochondria specific autophagy, ubiquitylates BAX K128 and targets the pro apoptotic BCL-2 protein for proteasomal degradation.

SIGNOR-278529

P07288

Q96ST3

0

transcriptional regulation

down-regulates quantity by repression

0.2

Chromatin immunoprecipitation (ChIP) and DNA affinity precipitation analysis demonstrated that Ebp1 and Sin3A associate at the PSA and E2F1 promoters. Functionally, Sin3A enhanced the ability of Ebp1 to repress transcription of androgen receptor (AR) and E2F1 regulated genes.

SIGNOR-253663

Q9GZQ8

P19484

0

transcriptional regulation

up-regulates quantity by expression

0.391

As expected, we found that glucose deprivation induced the binding of TFEB (Figure S4C) and ACSS2 (Figure S4D) to the promoter regions of MAP1LC3B, ATG3, and WIPI-1 as well as mRNA (Figure 3H) and protein (Figure 3I) expression of these genes;

SIGNOR-276559

P17252

P47712

1

phosphorylation

up-regulates

0.564

Pkcalfa, but not pkcbeta, is the predominant cpkc isoenzyme required for cpla2 protein phosphorylation and maximal induction of cpla2 enzymatic activity.

SIGNOR-149406

O95235

Q15173

0

dephosphorylation

up-regulates activity

0.2

We identify MKlp2 as an essential protein for promoting abscission, which may regulate tethering and stabilizing of the PM to the microtubule cytoskeleton. Aurora B phosphorylation of MKlp2 S878 in the LAM is a key inhibitory signal for abscission. Conversely, B56-PP2A promotes abscission by opposing Aurora B phosphorylation of MKlp2 S878.

SIGNOR-262660

P18669

Q16512

0

phosphorylation

down-regulates

0.254

Activated pak1 inhibits glycolysis by association of its catalytic domain with pgam-b and subsequent phosphorylation of the enzyme on serine residues 23 and 118, thereby abolishing pgam activity.

SIGNOR-91602

P31749

Q9BWT1

1

phosphorylation

down-regulates

0.338

The prosurvival kinase akt phosphorylates cdca7 at threonine 163, promoting binding to 14-3-3, dissociation from myc, and sequestration to the cytoplasm. we have mapped the domains of interaction and have discovered that akt phosphorylates cdca7 near this contact region, leading to loss of its association with myc, binding to 14-3-3 proteins, and exclusion from the nucleus.

SIGNOR-252533

Q16825

P12931

1

dephosphorylation

up-regulates

0.643

Ptpd1 activates src tyrosine kinase and increases the magnitude and duration of epidermal growth factor (egf) signaling.

SIGNOR-124774

P69905

P15289

0

acetylation

up-regulates activity

0.2

ASA acetylates hemoglobin. Purified acetylated hemoglobin had a slightly increased oxygen affinity and decreased heme-heme interaction.

SIGNOR-251773

Q15910

Q13315

0

phosphorylation

down-regulates quantity

0.458

Enhancer of zeste homolog 2 (EZH2), a core catalytic component of polycomb repressive complex 2, is a new ATM kinase target, and ATM-mediated phosphorylation of EZH2 on Ser734 reduces protein stability.|We verified that S734 is the predominant ATM site on EZH2 by performing ATM in vitro kinase assays using GST-EZH2 fusion proteins as substrates (Fig. 2b). The phosphorylation signal was nearly lost when the EZH2-S734A mutant was used as substrate

SIGNOR-279586

Q05086

O60936

1

ubiquitination

down-regulates quantity by destabilization

0.2

Incubation of transfected HEK293T cells with the proteasome inhibitor, MG132 blocked Ube3A mediated degradation of Arc suggesting that Ube3A degrades Arc via the ubiquitin proteasome system .|The ubiquitination of Arc by Ube3A was confirmed by mass spectrometry which revealed that Ube3A catalyzed the polyubiquitination of Arc on Lysine 268 and 269 ( xref ).

SIGNOR-278522

P98172

Q12923

0

dephosphorylation

up-regulates activity

0.708

Loss of PTPN13 function increases EFNB1 phosphorylation, enhances EFNB1 's interaction with ERBB1 and correlates with potentiated ERK1/2 activation.|Moreover, acquisition of PTPN13 loss-of-function mutations or its decreased expression (due to HPV infection or epigenetic silencing) may further enhance ERBB1 and EFNB1 mediated signals.

SIGNOR-277002

O15054

P68431

1

demethylation

down-regulates activity

0.2

Ubiquitously Transcribed Tetratricopeptide Repeat on chromosome X (UTX) and Jumonji D3 (JMJD3) as novel histone demethylases that catalyze the removal of di- and trimethyl groups on histone H3 lysine 27, thereby promoting target gene activation.

SIGNOR-260018

P24941

P30305

0

dephosphorylation

up-regulates activity

0.767

CDC25B is also able to dephosphorylate and activate CDK2-Cyclin A and CDK2-Cyclin E complexes [ xref \u2013 xref ].

SIGNOR-277140

P31751

Q99683

1

phosphorylation

down-regulates activity

0.646

Akt2 interacts with and phosphorylates ask1 at ser-83 resulting in inhibition of its kinase activity

SIGNOR-100588

P19784

Q99250

1

phosphorylation

up-regulates activity

0.2

We found that the ankyrin-binding motif of Na(v)1.2 that determines channel concentration at the AIS depends on a glutamate residue (E1111), but also on several serine residues (S1112, S1124, and S1126). We showed that phosphorylation of these residues by protein kinase CK2 (CK2) regulates Na(v) channel interaction with ankyrins. | inhibition of CK2 activity reduced sodium channel accumulation at the AIS of neurons. In conclusion, CK2 contributes to sodium channel organization by regulating their interaction with ankyrin G.

SIGNOR-275758

P61586

Q7Z628

0

guanine nucleotide exchange factor

up-regulates activity

0.832

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-260561

Q13315

Q9HA47

1

phosphorylation

down-regulates quantity by destabilization

0.2

ATM also phosphorylates UCK1 at S145, significantly enhancing the KLHL2-UCK1 complex formation|We demonstrated that the ubiquitin E3 ligase KLHL2 interacted with UCK1 and mediated its polyubiquitination at the K81 residue and degradation.

SIGNOR-275963

Q9UBE8

P46531

1

phosphorylation

down-regulates

0.382

Nlk-phosphorylated notch1icd is impaired in its ability to form a transcriptionally_ active_ ternary_ complex.

SIGNOR-163697

Q9P1W9

O95644

1

phosphorylation

up-regulates activity

0.261

In addition to PIM1, also PIM2 and PIM3 were able to phosphorylate WT, but not MM NFATC1 in vitro (Fig. (Fig.22c).

SIGNOR-276772

Q9BV73

Q9H0K1

0

phosphorylation

down-regulates

0.321

Here, we show that the salt inducible kinase 2 (sik2) localizes at the centrosome, plays a key role in the initiation of mitosis, and regulates the localization of the centrosome linker protein, c-nap1, through s2392 phosphorylation

SIGNOR-167488

Q05397

P06213

0

phosphorylation

up-regulates activity

0.353

P125(Fak) sequence comprising amino acids 568-582, which contains tyrosines 576 and 577 of the kinase domain regulatory loop, is phosphorylated by the insulin receptor. p125(Fak) phosphorylation by the receptor results in its activation.

SIGNOR-251323

Q13547

P49715

1

transcriptional regulation

down-regulates

0.436

These data suggest that c/ebp beta activates a single unified pathway of adipogenesis involving its stimulation of ppargamma expression, which then activates c/ebp alpha expression by dislodging hdac1 from the promoter for degradation in the proteasome

SIGNOR-210013

P06239

P41240

0

phosphorylation

down-regulates

0.538

P50csk tyrosine kinase phosphorylates p56lck at tyr-505 and down regulates its catalytic activity.

SIGNOR-20371

Q13224

P60484

0

dephosphorylation

down-regulates activity

0.296

GluN2B Y1472 site is dephosphorylated by PTEN .

SIGNOR-277165

O60566

P25054

1

phosphorylation

up-regulates activity

0.428

These findings support a model in which BubR1 kinase may directly regulate APC function involved in stable kinetochore microtubule attachment.|Using purified components, BubR1 directly phosphorylates APC and forms a ternary complex with APC and microtubules.

SIGNOR-279393

P00533

Q9ULU4

0

transcriptional regulation

down-regulates quantity by repression

0.2

Our quantitative ChIP experiments confirmed that ZMYND8 and JARID1D were co-localized at Slug, CD44, VEGFA, and EGFR genes (Figures 4F–4I). Our ChIP results also showed that ZMYND8 repressed and occupied other JARID1D target genes, such as the matrix metalloproteinase 1 (MMP1) and MMP3, that we previously reported

SIGNOR-262040

Q86YT6

Q00535

0

phosphorylation

up-regulates activity

0.325

Similar to the mechanism of PAR-1 regulation of Mib in neurogenesis, CDK5 phosphorylation is proposed to enhance Mib1 ligase activity leading to destabilization.|The cyclin dependent kinase 5 (CDK5) enriched in neurons phosphorylates Mib1 and suppresses the inhibitory effects of Mib1 on neurite morphology.

SIGNOR-280217

Q9UQL6

P17612

0

phosphorylation

up-regulates activity

0.2

PKA/Cdk5-mediated phosphorylation of HDAC5 at Ser279 within the NLS promotes nuclear localization of HDAC5 and interaction with the nuclear corepressor complex

SIGNOR-198658

Q9NPI1

Q13315

0

phosphorylation

down-regulates activity

0.2

ATM Directly Phosphorylates BRD7 at Ser 263 Site.

SIGNOR-279780

P31751

Q96B36

1

phosphorylation

down-regulates

0.674

Insulin-stimulated phosphorylation of pras40 by akt/pkb suppresses its mtorc1 inhibitory activity.

SIGNOR-153931

P68400

Q6VY07

1

phosphorylation

up-regulates activity

0.545

Phosphorylation of Ser278 by CK2 or a Ser278-->Asp mutation increased the interaction between PACS-1 and cargo, whereas a Ser278-->Ala substitution decreased this interaction. Moreover, the Ser278-->Ala mutation yields a dominant-negative PACS-1 molecule that selectively blocks retrieval of PACS-1-regulated cargo molecules to the TGN.

SIGNOR-250925

P53350

Q2NKX8

1

relocalization

up-regulates

0.88

Human pich was identified as an interaction partner and substrate of plk1. Our data indicate that plk1 prevents the association of pich with chromosome arms and restricts its localization to the kt/centromere region

SIGNOR-152136

P06241

P15498

1

phosphorylation

up-regulates

0.636

Study of t cells from a fyn-deficient tcr transgenic mouse also showed that fyn was required for tyrosine phosphorylation and activation of vav induced by both antagonist and agonist peptides.

SIGNOR-82287

Q92585

P68431

1

acetylation

down-regulates activity

0.2

The n-terminal domain of maml1 directly interacts with both p300 and histones, and the p300-maml1 complex specifically acetylates histone h3 and h4 tails in chromatin.

SIGNOR-153038

P61586

Q9NRY4

0

gtpase-activating protein

down-regulates activity

0.893

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-260492

P01106

P52789

1

transcriptional regulation

up-regulates quantity

0.37

Here, using the P493-6 Burkitt's lymphoma model with an inducible MYC, we demonstrate that HIF-1 cooperates with dysregulated c-Myc to promote glycolysis by induction of hexokinase 2, which catalyzes the first step of glycolysis, and pyruvate dehydrogenase kinase 1, which inactivates pyruvate dehydrogenase and diminishes mitochondrial respiration.

SIGNOR-259986

Q9ULU4

P16070

1

transcriptional regulation

down-regulates quantity by repression

0.2

Our quantitative ChIP experiments confirmed that ZMYND8 and JARID1D were co-localized at Slug, CD44, VEGFA, and EGFR genes (Figures 4F–4I). Our ChIP results also showed that ZMYND8 repressed and occupied other JARID1D target genes, such as the matrix metalloproteinase 1 (MMP1) and MMP3, that we previously reported

SIGNOR-262039

Q96PH1

P17252

0

phosphorylation

up-regulates

0.2

A constitutively active form of pkc? Robustly increased basal and pma-stimulated nox5 activity and promoted the phosphorylation of nox5 on ser490, thr494, and ser498.

SIGNOR-204550

P53350

Q00987

1

phosphorylation

up-regulates

0.465

Here we show that the oncogenic and cell cycle-regulatory protein kinase, polo-like kinase-1 (plk1), phosphorylates mdm2 at one of these residues, ser260, and stimulates mdm2-mediated turnover of p53. These data are consistent with the idea that deregulation of plk1 during tumourigenesis may help suppress p53 function.

SIGNOR-94272

Q6JBY9

Q16644

0

phosphorylation

down-regulates activity

0.482

Human CapZIP was phosphorylated at Ser-179 and Ser-244 by MAPKAP-K2 (mitogen-activated protein kinase-activated protein kinase 2) or MAPKAP-K3 in vitro. In the present paper we have identified CapZIP as a protein that is phosphorylated exceptionally rapidly by several SAPKs in vitro (Figure 4), and which is expressed in muscles and immune cells. Both MAPKAP-K2 and MAPKAP-K3 phosphorylated CapZIP at Ser-179 in vitro. An important clue to the function of CapZIP and its phosphorylation came from the finding that it binds to the actin-capping protein CapZ (Figure 7A), and that cellular stresses trigger the dissociation of these two proteins (Figure 7B).Such an effect is presumably lost when CapZIP is phosphorylated and dissociates from CapZ.

SIGNOR-263082

Q8TAQ5

Q13315

0

phosphorylation

down-regulates activity

0.459

These results indicate that Apak is a genuine substrate of ATM kinase. Apak phosphorylation on Ser 68 is critical for p53-mediated apoptosis. in response to DNA damage, ATM is rapidly activated by autophosphorylation and mediates p53 activation through disruption of the Apak–p53 complex by phosphorylating Apak on Ser 68.

SIGNOR-273513

P56178

P10451

1

transcriptional regulation

up-regulates quantity

0.373

Dlx5 initiates a complete osteogenic differentiation in these early primary cells, by triggering Runx2, osteopontin, alkaline phosphatase, and other gene expression according to the sequential temporal sequence observed during skull osteogenesis in vivo.

SIGNOR-245340

P45984

P45985

0

phosphorylation

up-regulates

0.729

Mkk4, which activates p38gamma, p38delta, and jnk2 to phosphorylate p53 on ser-33 and cause a transient g(1) arrest. A map kinase kinase kinase (mapkkk), termed ask1, was identified that activated two different subs of map kinase kinases (mapkk), sek1 (or mkk4) and mkk3/mapkk6 (or mkk6), which in turn activated stress-activated protein kinase (sapk, also known as jnk;c-jun amino-terminal kinase) here we report that mkk4 shows a striking preference for the tyrosine residue (tyr-185), and mkk7 a striking preference for the threonine residue (thr-183) in three sapk1/jnk1 isoforms tested (jnk1 alpha 1, jnk2 alpha 2 and jnk3 alpha 1)

SIGNOR-197998

P12931

Q96J92

1

phosphorylation

down-regulates activity

0.2

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

SIGNOR-276897

O94782

P06493

0

phosphorylation

up-regulates activity

0.371

In this study, we show that Ser313 phosphorylation in USP1 is required for its interaction with UAF1 and for the stimulation of USP1's activity. We further demonstrated that CDK1 is responsible for Ser313 phosphorylation, and protein phosphatase treatment of USP1 can lead to inactivation of USP1/UAF1.

SIGNOR-276423

P68431

P11309

0

phosphorylation

down-regulates activity

0.2

Pim1-dependent phosphorylation of histone h3 at serine 10 is required for myc-dependent transcriptional activation and oncogenic transformation.

SIGNOR-156946

P04637

P45983

0

phosphorylation

up-regulates

0.796

Activated jnk phosphorylates p53

SIGNOR-59812

P24844

P17252

0

phosphorylation

down-regulates

0.278

Rlc can also be phosphorylated at ser1/ser2/thr9 by protein kinase c (pkc). Biophysical studies show that phosphorylation at these sites leads to an increase in the km of myosin light chain kinase (mlck) for rlc, thereby indirectly inhibiting myosin ii activity

SIGNOR-192792

Q00535

P35222

1

phosphorylation

up-regulates activity

0.371

By combining multiple network relations with PTM proteoform specific functional information, we proposed a mechanism to explain the observation that the cyclin dependent kinase CDK5 positively regulates beta-catenin co-activator activity.|CDK5 phosphorylates beta-catenin on Ser 191 and Ser 246 (PR :000037229)

SIGNOR-279516

Q96JH7

P06493

0

phosphorylation

down-regulates activity

0.537

We clarified that VCIP135, an essential factor in both p97 membrane fusion pathways, is phosphorylated on Threonine-760 and Serine-767 by Cdc2 at mitosis and that this phosphorylated VCIP135 does not bind to p97.

SIGNOR-265038

P67775

Q8TD08

1

dephosphorylation

down-regulates

0.289

Erk8 (extracellular-signal-regulated protein kinase 8) expressed in escherichia coli or insect cells was catalytically active and phosphorylated at both residues of the thr-glu-tyr motif. Dephosphorylation of the threonine residue by pp2a (protein serine/threonine phosphatase 2a) decreased erk8 activity by over 95% in vitro, whereas complete dephosphorylation of the tyrosine residue by ptp1b (protein tyrosine phosphatase 1b) decreased activity by only 15-20%

SIGNOR-142977

P56545

Q9UNE7

0

ubiquitination

down-regulates quantity by destabilization

0.331

Our data showed that CHIP depletion resulted in up-regulation of the steady-state level of CtBP2 ( Fig. 1 B) and that CHIP ubiquitinated CtBP2 for proteasomal degradation ( Fig. 3 A).

SIGNOR-278722

P05771

P49768

1

phosphorylation

up-regulates activity

0.2

A phosphorylation site at serine residue 346 was identified that is selectively phosphorylated by PKC but not by PKA. This site is localized within a recognition motif for caspases, and phosphorylation strongly inhibits proteolytic processing of PS1 by caspase activity during apoptosis.

SIGNOR-249237

P17096

Q03135

0

relocalization

up-regulates activity

0.265

CAV1 was shown to stimulate GLUT3 transcription via an HMGA1-binding site within the GLUT3 promoter. HMGA1 was found to interact with and activate the GLUT3 promoter and CAV1 increased the HMGA1 activity by enhancing its nuclear localization.

SIGNOR-254428

Q9Y2K6

O95714

0

ubiquitination

down-regulates quantity

0.372

HERC2 promotes USP20 degradation.|Under unperturbed condition, HERC2 ubiquitinates USP20 and promotes ubiquitination mediated proteasomal degradation of USP20, regulating the status of K48 linked polyubiquitination of CLASPIN and ensuring appropriate protein levels of CLASPIN during the S-phase.

SIGNOR-278692

P35790

Q13535

0

phosphorylation

up-regulates activity

0.248

In particular, ATR phosphorylates Chk 1 and ATM signals to Chk 2.

SIGNOR-280184

P52333

P17706

0

dephosphorylation

down-regulates activity

0.697

Upon ligand binding, IL-2R , IL-6R or LeptinR , IFN-_R , IFN-_R and PRLR or growth hormone (GH) receptor associated JAKs become activated. These JAKs mediate phosphorylation of specific tyrosine residues and recruit STATs. Activated STATs are released from the receptor and translocate to the nucleus. PTP1B dephosphorylates JAK2, TYK2 and STAT5 . The 45-kDa form of TC-PTP was shown to dephosphorylate JAK1 and JAK3 as well as STAT1, STAT3 and STAT5.

SIGNOR-133078

P31749

P08670

1

phosphorylation

up-regulates quantity by stabilization

0.647

The binding of akt (tail region) to vim (head region) results in vim ser39 phosphorylation enhancing the ability of vim to induce motility and invasion while protecting vim from caspase-induced proteolysis.

SIGNOR-252511

Q13153

P41182

1

phosphorylation

down-regulates activity

0.2

The transcriptional repressor B-cell lymphoma (BCL)-6 downregulates genes involved in cell-cycle progression and becomes inactivated following phosphorylation by the Rac1 GTPase-activated protein kinase PAK1.

SIGNOR-253930

P45452

P02458

1

cleavage

down-regulates quantity by destabilization

0.544

Although it appears that MMP-1 and MMP-13 both cleave type II collagen initially at the same site, MMP-13 affects a secondary cleavage to produce a 1/4-size collagen fragment with an NH2 terminus three amino acids removed from the primary cleavage site.The present work has demonstrated expression of MMP-13 in human osteoarthritic cartilage and shown that MMP-13 has significant type II collagen degrading activity.

SIGNOR-256340

P31749

P49841

1

phosphorylation

down-regulates activity

0.792

Active AKT, a common mediator of cell survival signals induced by radiation through multiple intracellular signaling pathways,11, 12 suppresses apoptosis. AKT positively regulates cyclin D1 expression through inactivation of glycogen synthase kinase 3beta (GSK3B). The AKT-mediated phosphorylation of glycogen synthase kinase 3b on serine9 decreases its kinase activity for Thr286 of cyclin D1, which inhibits the nuclear export and the cytoplasmic proteasomal degradation of cyclin D1

SIGNOR-245416

Q13188

Q9UL54

0

phosphorylation

up-regulates

0.274

In addition, the thousand-and-one (tao) amino acids kinase or taok13 has been shown to directly phosphorylate and activate hpo or mst1/2.

SIGNOR-201327

P33981

P00519

1

phosphorylation

down-regulates

0.279

Ttk phosphorylation of thr735 was associated with partial inhibition of nuclear targeting of c-abl.

SIGNOR-181064

P00533

P27361

0

phosphorylation

down-regulates

0.557

It is likely that the map2 and ert kinases account for the phosphorylation of the egf receptor at thr669 (egf receptor (krel veplt669psgeapnqallr)) observed in cultured cells.Phosphorylation at ser-695 is partial and occurs only if thr-693 is phosphorylated. Phosphorylation at thr-678 and thr-693 by prkd1 inhibits egf-induced mapk8/jnk1 activation.

SIGNOR-20549

P18206

P12931

0

phosphorylation

down-regulates activity

0.76

The phosphorylation of vinculin on tyrosine residues 100 and 1065, mediated by SRC kinases, affects cell spreadingWhen phosphorylated, the vinculin tail exhibited significantly less binding to the vinculin head domain than the unphosphorylated tail.

SIGNOR-247424

Q15375

P56915

0

transcriptional regulation

down-regulates quantity by repression

0.2

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

SIGNOR-261613

Q08211

P35637

0

relocalization

down-regulates activity

0.482

We found that ALS mutants of FUS co-localized with Caprin-1, DDX3X, and DHX9 in cytoplasmic inclusions that could lead to the mis-regulation of their respective pathways, providing further clues to the mechanism of ALS pathogenesis.|FUS interacting proteins were sequestered into the cytoplasmic mutant FUS inclusions that could lead to their mis-regulation or loss of function, contributing to ALS pathogenesis. | We also demonstrated the co-localization of DHX9, DDX3X and Caprin-1 with cytoplasmic EGFP-P525L mutant FUS inclusions in primary cortical neurons

SIGNOR-262810

Q8IV63

O75531

1

phosphorylation

down-regulates activity

0.491

Although VRK3 has been regarded as a genuine pseudokinase from structural and biochemical studies, recent reports suggest that VRK3 acts as an active kinase as well as a signaling scaffold in cells. Here, we demonstrate that VRK3 phosphorylates the nuclear envelope protein barrier-to-autointegration factor (BAF) on Ser4.|Ectopic expression of VRK3 induces the translocation of BAF from the nucleus to the cytoplasm. I

SIGNOR-264564

P68400

P49427

1

phosphorylation

down-regulates activity

0.395

The ubiquitin-conjugating enzyme, cdc34, has been implicated in the ubiquitination of a number of vertebrate substrates, including p27(kip1), ikappabalpha, wee1, and myod. We show that mammalian cdc34 is a phosphoprotein that is phosphorylated in proliferating cells. Phosphorylation of cdc34 by the associated kinase maps predominantly to residues 203 and 222. Mutation of cdc34 at ck2-targeted residues, ser-203, ser-222, ser-231, thr-233, and ser-236, abolishes the phosphorylation of cdc34 observed in vivo and markedly shifts nuclearly localized cdc34 to the cytoplasm.

SIGNOR-110399

P01579

Q6NT76

0

transcriptional regulation

down-regulates quantity by repression

0.2

Additionally, by luciferase reporter assay, HMBOX1 displayed suppressive effect on the transcription activity of IFN-γ promoter.

SIGNOR-261625

P19784

P55087

1

phosphorylation

down-regulates activity

0.338

We found that the stress-induced kinase casein kinase (CK)II phosphorylates the Ser276 immediately preceding the tyrosine motif, increasing AQP4-mu 3A interaction and enhancing AQP4-lysosomal targeting and degradation. | To determine whether Ser276 is an actual CKII substrate, we used GST–AQP4‐Cter proteins in which only one out of the three C‐terminal CKII consensus sites was sequentially conserved (Ser276, Ser285 and Ser315, respectively). Figure 7B (right panel) shows that the three serine residues, including Ser276, were indeed efficiently phosphorylated by CKII.

SIGNOR-250976

P68400

Q01892

1

phosphorylation

down-regulates

0.429

Serine residues 37 in the transactivation domain and 129, 144 and 146 in the pest domain of spi-b are phosphorylated by ckii in vitro. The ckii phosphorylation sites mapped in vitro are phosphorylated in vivo. Mutations of the ckii phosphorylation sites increase the ability of spi-b to transactivate. Spi-b phosphorylation by ckii reduces its stability

SIGNOR-73891

Q8IW41

Q12778

1

phosphorylation

up-regulates activity

0.422

The kinase MK5 phosphorylates and activates Foxo1 at serine 215, and this modification is required for Foxo1 to induce Rag transcription.

SIGNOR-280037

P04040

Q16236

0

transcriptional regulation

up-regulates quantity by expression

0.426

BTG2 was found to up-regulate expression of antioxidant enzymes known to be regulated by NFE2L2, including catalase, SOD1, and SOD2

SIGNOR-254651

Q15139

O94768

1

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

P00519

P32119

1

phosphorylation

down-regulates activity

0.284

Inactivation of peroxiredoxin I by phosphorylation allows localized H(2)O(2) accumulation for cell signaling. To determine whether Prxs are phosphorylated, we subjected recombinant human PrxI and II to an in vitro kinase assay with two nonreceptor PTKs, Lck and Abl, in the presence of [γ-32P]ATP. Both PTKs phosphorylated PrxI and PrxII. Phosphorylation of the wild-type protein was detected, whereas that of the Y194F mutant was not (Figure 1B), indicating that Tyr194 is the only site of tyrosine phosphorylation.

SIGNOR-276280

P68431

Q9C0A6

0

methylation

up-regulates activity

0.2

SETD5 Exhibits Intrinsic Methyltransferase Activity on H3K36. This assay showed that SETD5 has specific histone methyltransferase activity toward K36 but not for other residues such as K4 and K27 (Figure 8B). we revealed that SETD5 is endowed with H3K36 methyltransferase, which is necessary for RNA elongation and processing and, ultimately, correct gene transcription.

SIGNOR-264620

P04637

P68400

0

phosphorylation

up-regulates activity

0.668

Furthermore, we demonstrate that anisomycin- and tumor necrosis factor-alpha-induced phosphorylation of p53 at Ser-392, which is important for the transcriptional activity of this growth suppressor protein, requires p38 MAP kinase and CK2 activities.

SIGNOR-250967

P28482

P36956

1

phosphorylation

up-regulates

0.406

Map kinases erk1/2 phosphorylate sterol regulatory element-binding protein (srebp)-1a at serine 117 in vitro. mutation of serine 117 to alanine abolished erk2-mediated phosphorylation in vitro and the map kinase-related transcriptional activation of srebp-1a by insulin and platelet-derived growth factor in vivo.

SIGNOR-80092

P19474

Q13501

1

ubiquitination

down-regulates activity

0.404

TRIM21 directly ubiquitylates p62 at residue K7 to inhibit its oligomerization and sequestration function.|TRIM21 negatively regulates p62 mediated sequestration of Keap1 and antioxidant response.

SIGNOR-278602

O00141

P46527

1

phosphorylation

down-regulates

0.469

Activated sgk1 and p27 phosphorylation at t157, and both were inhibited by short-term rapamycin treatment and by sgk1 shrna.

SIGNOR-179117

P06400

O96017

0

phosphorylation

up-regulates activity

0.423

Phosphorylation of prb at ser612 by chk1/2 leads to a complex between prb and e2f-1 after dna damageprb inhibits cell cycle progression through interactions with the e2f family of transcription factors. Here, we report that dna damage induced not only the dephosphorylation of prb at cdk phosphorylation sites and the binding of prb to e2f-1, but also the phosphorylation of prb at ser612. Phosphorylation of prb at ser612 enhanced the formation of a complex between prb and e2f-1

SIGNOR-153908

O95786

P68400

0

phosphorylation

down-regulates

0.2

Threonine at amino acid (aa) 770 and serine at aa 854 to 855 of rig-i are phosphorylated by casein kinase ii (ck2) in the resting state of the cell and dephosphorylated when cells are infected by rna virus. Mutation at aa position 770 or 854 to 855 of rig-i renders it constitutively active

SIGNOR-169404

Q12809

Q96PU5

0

ubiquitination

down-regulates quantity by destabilization

0.399

As quantified in Fig. 5 B, only Nedd4-2 significantly increased the basal ubiquitylation of hERG1, while Nedd4-2-C801S and the other ubiquitin ligases had no effect.|The major findings of this study are as follows : 1) hERG1 interacts via its PY motif with the ubiquitin ligase Nedd4-2, 2) this interaction promotes the down-regulation of the functional form of the channel at the plasma membrane through Nedd4-2 ubiquitylation of the channel, and 3) I hERG1 is strongly decreased by Nedd4-2 catalytic dependent activity.The hERG1 PY motif is a highly conserved sequence across animal species lines, highlighting its crucial role in the regulation of the hERG1 channel at the cell surface.

SIGNOR-278771