GleghornLab/Signor_2class · Datasets at Hugging Face

IdA string	IdB string	labels int64	mechanism string	effect string	score float64	sentence string	signor_id string
Q13131	P60891	1	phosphorylation	down-regulates activity	0.2	We demonstrate here that glucose deprivation or hypoxia results in the AMPK-mediated phosphorylation of phosphoribosyl pyrophosphate synthetase 1 (PRPS1) S180 and PRPS2 S183, leading to conversion of PRPS hexamers to monomers and thereby inhibiting PRPS1/2 activity, nucleotide synthesis, and nicotinamide adenine dinucleotide (NAD) production.	SIGNOR-265729
O15528	O95243	0	transcriptional regulation	up-regulates quantity by expression	0.377	Phosphorylation of MBD4 promotes 5-meC glycosylase activity Further evidence emerged to support the involvement of MBD4 in active demethylation. Protein-kinase C phosphorylation of MBD4 at two specific serine residues (165 and 262) following parathyroid hormone stimulation was shown to promote demethylation within the CYP27B1 gene promoter [12]	SIGNOR-275682
Q06210	Q13131	0	phosphorylation	down-regulates	0.2	Amp-activated protein kinase phosphorylates glutamine : fructose-6-phosphate amidotransferase 1 at ser243 to modulate its enzymatic activityhe 2-dg induced phosphorylation of gfat1 . The assay of the gfat enzymatic activity in the cell lysates indicated that the 2-dg-treatment inhibited the enzymatic activity	SIGNOR-183528
Q9NYY3	Q13627	0	phosphorylation	up-regulates quantity by stabilization	0.313	In the present study, it was demonstrated that dual specificity tyrosine-phosphorylation-regulated kinase 1A (DYRK1A) interacts with and phosphorylates PLK2 at Ser358. DYRK1A-mediated phosphorylation of PLK2 increases its protein stability.	SIGNOR-277805
P31749	P09651	1	phosphorylation	down-regulates	0.412	Our data also suggest that akt negatively regulates hnrnp a1-mediated ires activity via phosphorylation at ser199.	SIGNOR-252519
Q9BZL6	P41182	1	phosphorylation	down-regulates activity	0.2	Prkd2 directly binds to Bcl6 and Prkd2-dependent phosphorylation of Bcl6 is necessary to constrain Bcl6 to the cytoplasm, thereby limiting TFH development.	SIGNOR-279651
Q13315	P29372	1	phosphorylation	up-regulates activity	0.265	ATM phosphorylates MPG at serine 172 (XREF_FIG).\|In summary, our results show that ATM and MPG are directly associated in vitro and in vivo, phosphorylation of MPG at serine 172 is dependent on ATM and that of loss of phospho ATM reduces MPG glycosylase activity.	SIGNOR-279004
P03372	P37231	1	transcriptional regulation	down-regulates quantity by repression	0.28	Our data show for the first time that eralpha binds to ppar response element and represses its transactivation	SIGNOR-140233
P49841	P49716	1	phosphorylation	down-regulates quantity by destabilization	0.384	Phosphorylation of C/EBPdelta by GSK-3beta is required for its degradation by FBXW7alpha.	SIGNOR-279180
Q6ZVD8	P05771	1	dephosphorylation	down-regulates quantity	0.328	Here we show that the two PHLPP isoforms, PHLPP1 and PHLPP2, also dephosphorylate the hydrophobic motif on PKC betaII, an event that shunts PKC to the detergent-insoluble fraction, effectively terminating its life cycle	SIGNOR-237039
P07948	P16885	1	phosphorylation	up-regulates activity	0.62	The phosphorylation of purified phospholipase C-gamma 1 (PLC-gamma 1) and PLC-gamma 2 by src-family-protein tyrosine kinases (PTKs) P56lck, p53/56lyn, p59hck, p59fyn, and p60src was studied in vitro. All five PTKs phosphorylated PLC-gamma 1 and PLC-gamma 2, suggesting that both PLC-gamma isozymes can be phosphorylated in cells by any of the src-family PTKs in response to the activation of cell surface receptors.	SIGNOR-249384
P60891	Q9UHD2	0	phosphorylation	up-regulates activity	0.2	Here, we show that ionizing radiation results in TBK1-mediated phosphorylation of phosphoribosyl pyrophosphate synthetase (PRPS)1/2 at T228, thereby enhancing PRPS1/2 catalytic activity and promoting deoxyribonucleotide synthesis.	SIGNOR-277316
P01344	Q9H9Z2	0	translation regulation	up-regulates quantity by expression	0.397	Lin-28 binds IGF-2 mRNA and participates in skeletal myogenesis by increasing translation efficiency	SIGNOR-277339
P49336	Q15797	1	phosphorylation	down-regulates	0.383	Phosphorylation of the linker region of smad1, a receptor-activated smad (r-smad), at serine 206 (s206) and s214 induced by bmp and mediated by cdk8/9 is critical for binding of the e3 ubiquitin ligase smurf1. Binding of smurf1 leads to polyubiquitination of smad1 and its degradation by the proteasome;cdk8 and cyclint-cdk9 showed a preference for s206 and s214 but also phosphorylated s186 and s195 in the case of smad1;and t179, s208 and s213 in the case of smad3.	SIGNOR-161626
Q6P2M8	O43432	1	phosphorylation	up-regulates	0.2	Here we report that activity-dependent translational initiation in cultured rat hippocampal neurons is enhanced by camki-mediated phosphorylation of ser1156 in eukaryotic initiation factor eif4gii (4gii).	SIGNOR-197190
P49327	Q9H7Z6	0	acetylation	down-regulates quantity by destabilization	0.2	Overexpression of Myc-KAT8 increased the acetylation level of endogenous FASN by 2.2-fold (Fig. 3C). In contrast, knockdown of KAT8 decreased endogenous FASN acetylation by as much as 55%	SIGNOR-267366
O75385	P17252	0	phosphorylation	down-regulates activity	0.2	ULK1 is phosphorylated by PKCalpha at S423 in vivo and in vitro.\|PKC\u03b1 phosphorylation of ULK1 does not change its kinase activity	SIGNOR-279558
P11161	P17676	1	transcriptional regulation	up-regulates quantity by expression	0.534	Ectopic expression of krox20 can transactivate the c/ebpbeta promoter and increase c/ebpbeta gene expression in 3t3-l1 preadipocytes	SIGNOR-139292
Q05209	P56945	1	dephosphorylation	down-regulates	0.546	Ptp-pest is an efficient negative regulator of lymphocyte activation. This function correlated with the ability of ptp-pest to induce dephosphorylation of shc, pyk2, fak and cas, and inactivate the ras pathway.	SIGNOR-109032
P05067	Q9NYY3	0	phosphorylation	up-regulates activity	0.348	Here we show that Polo-like kinase 2 (Plk2), an activity-inducible regulator of homeostatic plasticity, directly binds and phosphorylates threonine-668 and serine-675 of APP in\u00a0vitro and associates with APP in\u00a0vivo.\|Plk2 was necessary and sufficient to induce BACE-1-mediated APP amyloidogenic processing following overexcitation, associated intimately with APP, and directly phosphorylated the APP C-terminus.	SIGNOR-279424
P43403	Q9Y2R2	0	dephosphorylation	down-regulates	0.706	Native ptpn22 dephosphorylated lck and zap70 at their activating tyrosine residues tyr-394 and tyr-493, respectively, but not at the regulatory tyrosines tyr-505 (lck) or tyr-319 (zap70).	SIGNOR-144345
P19784	Q13144	1	phosphorylation	up-regulates activity	0.37	Two conserved sites (Ser712/713) are phosphorylated by casein kinase 2. They lie at the extreme C-terminus and are required for the interaction of eIF2Bepsilon with its substrate, eIF2, in vivo and for eIF2B activity in vitro.	SIGNOR-250990
O94875	P22681	0	ubiquitination	down-regulates	0.512	Cbl-argbp2 complex mediates ubiquitination and degradation of c-abl	SIGNOR-96325
Q8IUQ4	Q9H2X6	1	polyubiquitination	down-regulates quantity by destabilization	0.514	Here we demonstrate that HIPK2 is an unstable protein that colocalizes and interacts with the E3 ubiquitin ligase Siah-1 in unstressed cells. Siah-1 knockdown increases HIPK2 stability and steady-state levels, whereas Siah-1 expression facilitates HIPK2 polyubiquitination, degradation and thereby inactivation.	SIGNOR-276166
P49137	P34931	1	phosphorylation	up-regulates activity	0.2	We demonstrate that MK2 phosphorylates HspA1L solely on Ser241, a residue within the N-terminal nucleotide-binding domain of the enzyme. This phosphorylation event enhances the chaperone activity of HspA1L in vitro and renders male germ cells more resistant to heat stress-induced apoptosis.	SIGNOR-273674
Q8IWJ2	P51151	0	null	up-regulates activity	0.54	Rab9-dependent transport from late endosomes to the Golgi requires the Rab9 effectors p40 (Diaz et al., 1997) and TIP47 (Diaz and Pfeffer, 1998), a protein that recognizes the cytoplasmic domains of the two types of MPRs and packages them into nascent transport vesicles (Carroll et al., 2001). MPR recycling also utilizes a TGN-localized coiled-coil protein named GCC185 that is also a Rab9 effector	SIGNOR-253087
Q9NQU5	P52564	0	phosphorylation	up-regulates	0.2	Moreover, pak6 was directly activated by mkk6, and mutation of tyrosine 566 in a consensus mkk6 site (threonine-proline-tyrosine, tpy) in the activation loop of the pak6 kinase domain prevented activation by mkk6.	SIGNOR-130975
P52564	Q9NQU5	1	phosphorylation	up-regulates	0.2	Moreover, pak6 was directly activated by mkk6, and mutation of tyrosine 566 in a consensus mkk6 site (threonine-proline-tyrosine, tpy) in the activation loop of the pak6 kinase domain prevented activation by mkk6.	SIGNOR-130975
Q01844	P17252	0	phosphorylation	down-regulates activity	0.331	Here we report thatews, a nuclearrna-bindingprooncoprotein, contains an iq domain, is phosphorylated byproteinkinase c, and interacts with calmodulin. Interestingly, pkc phosphorylation of ews inhibits its binding to rna homopolymers, and conversely,rna binding to ews interferes with pkc phosphorylation./ these data indicate that ews contains an iq domain with ser266 acting as the primary site for pkc phosphorylation.	SIGNOR-52850
Q14258	Q9UKV5	1	polyubiquitination	down-regulates quantity by destabilization	0.364	We further demonstrate that TRIM25 ubiquitylates gp78 and that overexpression of TRIM25 accelerates the degradation of gp78. Our data suggest that TRIM25 not only cooperates with gp78 in polyubiquitylation of AMF but also gauges the steady-state level of gp78.	SIGNOR-272176
O96017	Q13315	0	phosphorylation	up-regulates activity	0.835	Phosphorylation and activation of chk2 are ataxia telangiectasia-mutated (atm) dependent in response to ir	SIGNOR-81403
Q92630	P04637	1	phosphorylation	up-regulates	0.67	Here, we demonstrate that the dual-specificity tyrosine-phosphorylation-regulated kinase 2 (dyrk2) directly phosphorylates p53 at ser46. these findings indicate that dyrk2 regulates p53 to induce apoptosis in response to dna damage.	SIGNOR-153544
P45452	P00748	1	cleavage	down-regulates quantity by destabilization	0.313	The data presented in this study show for the first time the degradation of Factor XII of the blood clotting system by matrix metalloproteinases. MMP-12, MMP-13, and MMP-14 cleave at Gly376Leu377\|However, no activity of Factor XII can be observed after MMPinduced cleavage.	SIGNOR-263609
O14965	O95239	1	phosphorylation	up-regulates activity	0.419	We show that Aurora A phosphorylates the condensin I-dependent pool of KIF4A and thus actively promotes chromosome congression from the spindle poles to the metaphase plate. In vitro kinase assays showed that recombinant KIF4A can be phosphorylated by Aurora A and that this activity is inhibited by the specific Aurora A inhibitor MLN8537 (Fig. 7 C).	SIGNOR-265993
P28482	Q12800	1	phosphorylation	down-regulates	0.335	We previously established that phosphorylation of lsf in early g1 at ser-291 and ser-309 inhibits its transcriptional activity and that dephosphorylation later in g1 is required for its reactivation. At the peak activities of erk and cyclin c/cdk2 in early g1, lsf is efficiently phosphorylated on ser-291 and ser-309.	SIGNOR-184168
Q04741	O14786	1	transcriptional regulation	up-regulates quantity by expression	0.2	EMX1 activates the transcription of Nrp1 in vitro.	SIGNOR-261593
Q02750	Q13233	0	phosphorylation	up-regulates activity	0.661	Phosphorylation at ser-218 and ser-222 by map kinase kinase kinases (raf or mekk1) positively regulates mek1 kinase activity.	SIGNOR-235587
P25490	P68400	0	phosphorylation	up-regulates	0.286	More recently, we identified and mapped multiple phosphorylation sites in yy1, including, threonine 39, serine 118, serine 247, threonine 348 and threonine 378. The first kinase proven to phosphorylate yy1 in vivo was plk1, which phosphorylates threonine 39 during g2/m stage of the cell cycle [25]. Ck2_ is another kinase identified as constitutively phosphorylating yy1 at serine 118. This modification protects yy1 cleavage by caspase 7 during apoptosis	SIGNOR-200083
Q9Y566	Q9Y2H0	0	relocalization	up-regulates activity	0.696	SHANK proteins are ‘master’ scaffolding proteins that tether and organize intermediate scaffolding proteins. They are located at excitatory synapses, where they are crucial for proper synaptic development and function. SAPAP proteins subsequently bind to the PDZ domain of members of the SHANK protein family. SHANK proteins then bind to the actin cytoskeleton and to Homer protein, which in turn interacts with mGluRs. Through these extended links, PSD95, SAPAP, SHANK and Homer proteins form a quaternary complex that brings together mGluR and NMDAR complexes in the PSD (FIG. 3).	SIGNOR-264595
Q03001	P10914	0	transcriptional regulation	down-regulates quantity by repression	0.2	Transient transfection studies with BPAG1 promoter-luciferase reporter gene plasmids and IRF1 and IRF2 expression plasmids revealed that IRF1 and IRF2 directly down-regulated BPAG1 gene transcription in cultured normal human epidermal keratinocytes.	SIGNOR-254492
Q15208	Q9Y5J3	1	phosphorylation	up-regulates activity	0.358	We have identified two related kinases, STK38 (serine/threonine kinase 38) and STK38L (serine/threonine kinase 38 like), which interact with and phosphorylate HEY1 at Ser-68.	SIGNOR-279489
Q8N5V2	Q00535	0	phosphorylation	up-regulates activity	0.42	Importantly, ephexin1, a Rho GEF, is phosphorylated by Cdk5 in vivo .	SIGNOR-279021
Q63HK5	P49662	1	transcriptional regulation	down-regulates quantity by repression	0.27	Chromatin immunoprecipitation showed a direct interaction of FE65 and Teashirt3 with the promoter region of CASP4. The results were consistent with a model in which reduced expression of Teashirt3, mediated by genetic or other causes, increases caspase-4 expression, leading to progression of AD.	SIGNOR-264815
Q15327	P01160	1	transcriptional regulation	down-regulates quantity by repression	0.326	In vitro calpain-mediated degradation assays, coupled to reporter gene analysis in transfected HeLa cells, strongly suggested that this mutation enhances both the stability of the ANKRD1/CARP protein and its transcriptional repression activity upon the cardiac-specific atrial natriuretic factor (ANF) promoter.	SIGNOR-253647
P37840	Q13627	0	phosphorylation	up-regulates	0.561	In vitro kinase assay of anti-dyrk1a immunocomplexes demonstrated that dyrk1a could phosphorylate alpha-synuclein at ser-87. Furthermore, aggregates formed by phosphorylated alpha-synuclein have a distinct morphology and are more neurotoxic compared with aggregates composed of unmodified wild type alpha-synuclein. These findings suggest alpha-synuclein inclusion formation regulated by dyrk1a, potentially affecting neuronal cell viability.	SIGNOR-149393
P27361	Q01860	1	phosphorylation	down-regulates	0.343	Phosphorylation of this site downregulates nanog, sox2, rex1 and upregulates bmp4, gata6, ddlx5.	SIGNOR-192101
O75581	P45983	0	phosphorylation	up-regulates	0.382	We show that several proline-directed mitogen-activated protein kinases (mapks), such as p38, erk1/2, and jnk1 are sufficient and required for the phosphorylation of ppps/tp motifs of lrp6. External stimuli, which control the activity of mapks, such as phorbol esters and fibroblast growth factor 2 (fgf2) control the choice of the lrp6-ppps/tp kinase and regulate the amplitude of lrp6 phosphorylation and wnt/beta-catenin-dependent transcription.	SIGNOR-169007
Q13131	O15360	1	phosphorylation	up-regulates activity	0.332	FANCA was phosphorylated by AMPK at S347 and phosphorylation increased with MMC treatment. MMC-induced FANCD2 monoubiquitination and nuclear foci formation were compromised in a U2OS cell line that stably overexpressed the S347A mutant form of FANCA compared to wild-type FANCA-overexpressing cells, indicating a requirement for FANCA phosphorylation at S347 for proper activation of the FA/BRCA pathway.	SIGNOR-277264
Q12778	Q9UBE8	0	phosphorylation	down-regulates activity	0.613	Here, we report that the transforming growth factor-beta-activated kinase (TAK1)-Nemo-like kinase (NLK) pathway negatively regulates FOXO1. We show that NLK binds and phosphorylates FOXO1 at Pro-directed Ser/Thr residues in the transactivation domain. The phosphorylation by TAK1-NLK pathway inhibits the transcriptional activity of FOXO1 and excludes FOXO1 from the nucleus, which is independent of phosphatidylinositol 3-kinase/Akt pathway.	SIGNOR-273907
Q04206	Q96EB6	0	deacetylation	down-regulates activity	0.722	SIRT1 physically interacts with the RelA/p65 subunit of NF-kappaB and inhibits transcription by deacetylating RelA/p65 at lysine 310.	SIGNOR-238817
P45984	P12931	1	phosphorylation	up-regulates activity	0.355	Activation of c-Src by JNK2 was accompanied by the phosphorylation of c-Src on threonine residue (s).\|JNK2 directly phosphorylates c-Src and activates its auto phosphorylation.	SIGNOR-279221
P31946	Q05655	0	phosphorylation	down-regulates	0.493	We provide a mechanism for these observations through the phosphorylation of 14-3-3 by ikk and pkc on serine residues ser132 and ser60, respectively, which interferes with its binding to ttp and hence the retention of ttp in the cytoplasm.	SIGNOR-138612
P04271	P09630	0	transcriptional regulation	up-regulates quantity by expression	0.2	HOXC6 and HOXC11 increase transcription of S100beta gene in BrdU-induced in vitro differentiation of GOTO neuroblastoma cells into Schwannian cells.	SIGNOR-261646
Q96P20	P45983	0	phosphorylation	up-regulates activity	0.369	Ethanol induced JNK1 phosphorylation activated the NLRP3 inflammasome that induced caspase-1 dependent mitophagy inhibition, thereby exacerbating ROS accumulation and causing cell death.\|However, recent studies suggested that Ser 194 phosphorylation of NLRP3 was essential for the control of inflammasome activation and that JNK1 directly phosphorylates NLRP3, which stimulates the self-association and oligomerization of NLRP3 [ xref , xref ].	SIGNOR-280034
Q9UKE5	Q9NQB0	1	phosphorylation	up-regulates	0.555	Here, we report that tnik is an activating kinase for tcf4 and essential for colorectal cancer growth. Tnik, but not its catalytically inactive mutant, phosphorylated the conserved serine 154 residue of tcf4.	SIGNOR-165946
P19544	O00592	1	transcriptional regulation	up-regulates quantity by expression	0.409	Binding of WT1 to conserved elements within the Podocalyxin gene promoter results in potent transcriptional activation, and the specific expression pattern of Podocalyxin in the developing kidney mirrors that of WT1 itself.	SIGNOR-252300
Q15116	Q06124	0	dephosphorylation	down-regulates activity	0.659	Related to the latter notion, we recently showed that SHP2 dephosphorylates PD-1 to disassemble the PD-1:SHP2 complex ( xref ).	SIGNOR-277052
P53779	P30307	1	phosphorylation	down-regulates	0.245	Here we show that jnk directly phosphorylates cdc25c at serine 168 during g(2) phase of the cell cycle. Cdc25c phosphorylation by jnk negatively regulates its phosphatase activity and thereby cdk1 activation, enabling a timely control of mitosis onset.	SIGNOR-164085
P35227	Q03933	1	sumoylation	down-regulates activity	0.325	MEL-18, in contrast to the polycomb protein PC2/CBX4, in which SUMO E3 activity stimulates sumoylation of certain proteins, actually functions like an anti-SUMO E3 protein, interacting with both HSF2 and the SUMO E2 UBC9 but acting to inhibit UBC9 activity and thereby decreasing sumoylation of a target protein, in this case that of HSF2. sumoylation of HSF2 is up-regulated during mitosis and is important for the interaction of this factor with a subunit of the condensin complex during the bookmarking process	SIGNOR-226245
Q92844	O95147	1	ubiquitination	up-regulates activity	0.2	TRAF2-mediated Lys63-linked ubiquitination of DUSP14/MKP6 is essential for its phosphatase activity. Mass spectrometry and mutational analyses identified that DUSP14 was Lys63-linked ubiquitinated at lysine 103 residue.Here we report that DUSP14 was Lys63-linked ubiquitinated at Lys103 residue by the E3 ligase TRAF2 during TCR signaling. Furthermore, ubiquitination of DUSP14 was essential for its phosphatase activity.	SIGNOR-272811

Q13131

P60891

1

phosphorylation

down-regulates activity

0.2

We demonstrate here that glucose deprivation or hypoxia results in the AMPK-mediated phosphorylation of phosphoribosyl pyrophosphate synthetase 1 (PRPS1) S180 and PRPS2 S183, leading to conversion of PRPS hexamers to monomers and thereby inhibiting PRPS1/2 activity, nucleotide synthesis, and nicotinamide adenine dinucleotide (NAD) production.

SIGNOR-265729

O15528

O95243

0

transcriptional regulation

up-regulates quantity by expression

0.377

Phosphorylation of MBD4 promotes 5-meC glycosylase activity Further evidence emerged to support the involvement of MBD4 in active demethylation. Protein-kinase C phosphorylation of MBD4 at two specific serine residues (165 and 262) following parathyroid hormone stimulation was shown to promote demethylation within the CYP27B1 gene promoter [12]

SIGNOR-275682

Q06210

Q13131

0

phosphorylation

down-regulates

0.2

Amp-activated protein kinase phosphorylates glutamine : fructose-6-phosphate amidotransferase 1 at ser243 to modulate its enzymatic activityhe 2-dg induced phosphorylation of gfat1 . The assay of the gfat enzymatic activity in the cell lysates indicated that the 2-dg-treatment inhibited the enzymatic activity

SIGNOR-183528

Q9NYY3

Q13627

0

phosphorylation

up-regulates quantity by stabilization

0.313

In the present study, it was demonstrated that dual specificity tyrosine-phosphorylation-regulated kinase 1A (DYRK1A) interacts with and phosphorylates PLK2 at Ser358. DYRK1A-mediated phosphorylation of PLK2 increases its protein stability.

SIGNOR-277805

P31749

P09651

1

phosphorylation

down-regulates

0.412

Our data also suggest that akt negatively regulates hnrnp a1-mediated ires activity via phosphorylation at ser199.

SIGNOR-252519

Q9BZL6

P41182

1

phosphorylation

down-regulates activity

0.2

Prkd2 directly binds to Bcl6 and Prkd2-dependent phosphorylation of Bcl6 is necessary to constrain Bcl6 to the cytoplasm, thereby limiting TFH development.

SIGNOR-279651

Q13315

P29372

1

phosphorylation

up-regulates activity

0.265

ATM phosphorylates MPG at serine 172 (XREF_FIG).|In summary, our results show that ATM and MPG are directly associated in vitro and in vivo, phosphorylation of MPG at serine 172 is dependent on ATM and that of loss of phospho ATM reduces MPG glycosylase activity.

SIGNOR-279004

P03372

P37231

1

transcriptional regulation

down-regulates quantity by repression

0.28

Our data show for the first time that eralpha binds to ppar response element and represses its transactivation

SIGNOR-140233

P49841

P49716

1

phosphorylation

down-regulates quantity by destabilization

0.384

Phosphorylation of C/EBPdelta by GSK-3beta is required for its degradation by FBXW7alpha.

SIGNOR-279180

Q6ZVD8

P05771

1

dephosphorylation

down-regulates quantity

0.328

Here we show that the two PHLPP isoforms, PHLPP1 and PHLPP2, also dephosphorylate the hydrophobic motif on PKC betaII, an event that shunts PKC to the detergent-insoluble fraction, effectively terminating its life cycle

SIGNOR-237039

P07948

P16885

1

phosphorylation

up-regulates activity

0.62

The phosphorylation of purified phospholipase C-gamma 1 (PLC-gamma 1) and PLC-gamma 2 by src-family-protein tyrosine kinases (PTKs) P56lck, p53/56lyn, p59hck, p59fyn, and p60src was studied in vitro. All five PTKs phosphorylated PLC-gamma 1 and PLC-gamma 2, suggesting that both PLC-gamma isozymes can be phosphorylated in cells by any of the src-family PTKs in response to the activation of cell surface receptors.

SIGNOR-249384

P60891

Q9UHD2

0

phosphorylation

up-regulates activity

0.2

Here, we show that ionizing radiation results in TBK1-mediated phosphorylation of phosphoribosyl pyrophosphate synthetase (PRPS)1/2 at T228, thereby enhancing PRPS1/2 catalytic activity and promoting deoxyribonucleotide synthesis.

SIGNOR-277316

P01344

Q9H9Z2

0

translation regulation

up-regulates quantity by expression

0.397

Lin-28 binds IGF-2 mRNA and participates in skeletal myogenesis by increasing translation efficiency

SIGNOR-277339

P49336

Q15797

1

phosphorylation

down-regulates

0.383

Phosphorylation of the linker region of smad1, a receptor-activated smad (r-smad), at serine 206 (s206) and s214 induced by bmp and mediated by cdk8/9 is critical for binding of the e3 ubiquitin ligase smurf1. Binding of smurf1 leads to polyubiquitination of smad1 and its degradation by the proteasome;cdk8 and cyclint-cdk9 showed a preference for s206 and s214 but also phosphorylated s186 and s195 in the case of smad1;and t179, s208 and s213 in the case of smad3.

SIGNOR-161626

Q6P2M8

O43432

1

phosphorylation

up-regulates

0.2

Here we report that activity-dependent translational initiation in cultured rat hippocampal neurons is enhanced by camki-mediated phosphorylation of ser1156 in eukaryotic initiation factor eif4gii (4gii).

SIGNOR-197190

P49327

Q9H7Z6

0

acetylation

down-regulates quantity by destabilization

0.2

Overexpression of Myc-KAT8 increased the acetylation level of endogenous FASN by 2.2-fold (Fig. 3C). In contrast, knockdown of KAT8 decreased endogenous FASN acetylation by as much as 55%

SIGNOR-267366

O75385

P17252

0

phosphorylation

down-regulates activity

0.2

ULK1 is phosphorylated by PKCalpha at S423 in vivo and in vitro.|PKC\u03b1 phosphorylation of ULK1 does not change its kinase activity

SIGNOR-279558

P11161

P17676

1

transcriptional regulation

up-regulates quantity by expression

0.534

Ectopic expression of krox20 can transactivate the c/ebpbeta promoter and increase c/ebpbeta gene expression in 3t3-l1 preadipocytes

SIGNOR-139292

Q05209

P56945

1

dephosphorylation

down-regulates

0.546

Ptp-pest is an efficient negative regulator of lymphocyte activation. This function correlated with the ability of ptp-pest to induce dephosphorylation of shc, pyk2, fak and cas, and inactivate the ras pathway.

SIGNOR-109032

P05067

Q9NYY3

0

phosphorylation

up-regulates activity

0.348

Here we show that Polo-like kinase 2 (Plk2), an activity-inducible regulator of homeostatic plasticity, directly binds and phosphorylates threonine-668 and serine-675 of APP in\u00a0vitro and associates with APP in\u00a0vivo.|Plk2 was necessary and sufficient to induce BACE-1-mediated APP amyloidogenic processing following overexcitation, associated intimately with APP, and directly phosphorylated the APP C-terminus.

SIGNOR-279424

P43403

Q9Y2R2

0

dephosphorylation

down-regulates

0.706

Native ptpn22 dephosphorylated lck and zap70 at their activating tyrosine residues tyr-394 and tyr-493, respectively, but not at the regulatory tyrosines tyr-505 (lck) or tyr-319 (zap70).

SIGNOR-144345

P19784

Q13144

1

phosphorylation

up-regulates activity

0.37

Two conserved sites (Ser712/713) are phosphorylated by casein kinase 2. They lie at the extreme C-terminus and are required for the interaction of eIF2Bepsilon with its substrate, eIF2, in vivo and for eIF2B activity in vitro.

SIGNOR-250990

O94875

P22681

0

ubiquitination

down-regulates

0.512

Cbl-argbp2 complex mediates ubiquitination and degradation of c-abl

SIGNOR-96325

Q8IUQ4

Q9H2X6

1

polyubiquitination

down-regulates quantity by destabilization

0.514

Here we demonstrate that HIPK2 is an unstable protein that colocalizes and interacts with the E3 ubiquitin ligase Siah-1 in unstressed cells. Siah-1 knockdown increases HIPK2 stability and steady-state levels, whereas Siah-1 expression facilitates HIPK2 polyubiquitination, degradation and thereby inactivation.

SIGNOR-276166

P49137

P34931

1

phosphorylation

up-regulates activity

0.2

We demonstrate that MK2 phosphorylates HspA1L solely on Ser241, a residue within the N-terminal nucleotide-binding domain of the enzyme. This phosphorylation event enhances the chaperone activity of HspA1L in vitro and renders male germ cells more resistant to heat stress-induced apoptosis.

SIGNOR-273674

Q8IWJ2

P51151

0

null

up-regulates activity

0.54

Rab9-dependent transport from late endosomes to the Golgi requires the Rab9 effectors p40 (Diaz et al., 1997) and TIP47 (Diaz and Pfeffer, 1998), a protein that recognizes the cytoplasmic domains of the two types of MPRs and packages them into nascent transport vesicles (Carroll et al., 2001). MPR recycling also utilizes a TGN-localized coiled-coil protein named GCC185 that is also a Rab9 effector

SIGNOR-253087

Q9NQU5

P52564

0

phosphorylation

up-regulates

0.2

Moreover, pak6 was directly activated by mkk6, and mutation of tyrosine 566 in a consensus mkk6 site (threonine-proline-tyrosine, tpy) in the activation loop of the pak6 kinase domain prevented activation by mkk6.

SIGNOR-130975

P52564

Q9NQU5

1

phosphorylation

up-regulates

0.2

Moreover, pak6 was directly activated by mkk6, and mutation of tyrosine 566 in a consensus mkk6 site (threonine-proline-tyrosine, tpy) in the activation loop of the pak6 kinase domain prevented activation by mkk6.

SIGNOR-130975

Q01844

P17252

0

phosphorylation

down-regulates activity

0.331

Here we report thatews, a nuclearrna-bindingprooncoprotein, contains an iq domain, is phosphorylated byproteinkinase c, and interacts with calmodulin. Interestingly, pkc phosphorylation of ews inhibits its binding to rna homopolymers, and conversely,rna binding to ews interferes with pkc phosphorylation./ these data indicate that ews contains an iq domain with ser266 acting as the primary site for pkc phosphorylation.

SIGNOR-52850

Q14258

Q9UKV5

1

polyubiquitination

down-regulates quantity by destabilization

0.364

We further demonstrate that TRIM25 ubiquitylates gp78 and that overexpression of TRIM25 accelerates the degradation of gp78. Our data suggest that TRIM25 not only cooperates with gp78 in polyubiquitylation of AMF but also gauges the steady-state level of gp78.

SIGNOR-272176

O96017

Q13315

0

phosphorylation

up-regulates activity

0.835

Phosphorylation and activation of chk2 are ataxia telangiectasia-mutated (atm) dependent in response to ir

SIGNOR-81403

Q92630

P04637

1

phosphorylation

up-regulates

0.67

Here, we demonstrate that the dual-specificity tyrosine-phosphorylation-regulated kinase 2 (dyrk2) directly phosphorylates p53 at ser46. these findings indicate that dyrk2 regulates p53 to induce apoptosis in response to dna damage.

SIGNOR-153544

P45452

P00748

1

cleavage

down-regulates quantity by destabilization

0.313

The data presented in this study show for the first time the degradation of Factor XII of the blood clotting system by matrix metalloproteinases. MMP-12, MMP-13, and MMP-14 cleave at Gly376Leu377|However, no activity of Factor XII can be observed after MMPinduced cleavage.

SIGNOR-263609

O14965

O95239

1

phosphorylation

up-regulates activity

0.419

We show that Aurora A phosphorylates the condensin I-dependent pool of KIF4A and thus actively promotes chromosome congression from the spindle poles to the metaphase plate. In vitro kinase assays showed that recombinant KIF4A can be phosphorylated by Aurora A and that this activity is inhibited by the specific Aurora A inhibitor MLN8537 (Fig. 7 C).

SIGNOR-265993

P28482

Q12800

1

phosphorylation

down-regulates

0.335

We previously established that phosphorylation of lsf in early g1 at ser-291 and ser-309 inhibits its transcriptional activity and that dephosphorylation later in g1 is required for its reactivation. At the peak activities of erk and cyclin c/cdk2 in early g1, lsf is efficiently phosphorylated on ser-291 and ser-309.

SIGNOR-184168

Q04741

O14786

1

transcriptional regulation

up-regulates quantity by expression

0.2

EMX1 activates the transcription of Nrp1 in vitro.

SIGNOR-261593

Q02750

Q13233

0

phosphorylation

up-regulates activity

0.661

Phosphorylation at ser-218 and ser-222 by map kinase kinase kinases (raf or mekk1) positively regulates mek1 kinase activity.

SIGNOR-235587

P25490

P68400

0

phosphorylation

up-regulates

0.286

More recently, we identified and mapped multiple phosphorylation sites in yy1, including, threonine 39, serine 118, serine 247, threonine 348 and threonine 378. The first kinase proven to phosphorylate yy1 in vivo was plk1, which phosphorylates threonine 39 during g2/m stage of the cell cycle [25]. Ck2_ is another kinase identified as constitutively phosphorylating yy1 at serine 118. This modification protects yy1 cleavage by caspase 7 during apoptosis

SIGNOR-200083

Q9Y566

Q9Y2H0

0

relocalization

up-regulates activity

0.696

SHANK proteins are ‘master’ scaffolding proteins that tether and organize intermediate scaffolding proteins. They are located at excitatory synapses, where they are crucial for proper synaptic development and function. SAPAP proteins subsequently bind to the PDZ domain of members of the SHANK protein family. SHANK proteins then bind to the actin cytoskeleton and to Homer protein, which in turn interacts with mGluRs. Through these extended links, PSD95, SAPAP, SHANK and Homer proteins form a quaternary complex that brings together mGluR and NMDAR complexes in the PSD (FIG. 3).

SIGNOR-264595

Q03001

P10914

0

transcriptional regulation

down-regulates quantity by repression

0.2

Transient transfection studies with BPAG1 promoter-luciferase reporter gene plasmids and IRF1 and IRF2 expression plasmids revealed that IRF1 and IRF2 directly down-regulated BPAG1 gene transcription in cultured normal human epidermal keratinocytes.

SIGNOR-254492

Q15208

Q9Y5J3

1

phosphorylation

up-regulates activity

0.358

We have identified two related kinases, STK38 (serine/threonine kinase 38) and STK38L (serine/threonine kinase 38 like), which interact with and phosphorylate HEY1 at Ser-68.

SIGNOR-279489

Q8N5V2

Q00535

0

phosphorylation

up-regulates activity

0.42

Importantly, ephexin1, a Rho GEF, is phosphorylated by Cdk5 in vivo .

SIGNOR-279021

Q63HK5

P49662

1

transcriptional regulation

down-regulates quantity by repression

0.27

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

SIGNOR-264815

Q15327

P01160

1

transcriptional regulation

down-regulates quantity by repression

0.326

In vitro calpain-mediated degradation assays, coupled to reporter gene analysis in transfected HeLa cells, strongly suggested that this mutation enhances both the stability of the ANKRD1/CARP protein and its transcriptional repression activity upon the cardiac-specific atrial natriuretic factor (ANF) promoter.

SIGNOR-253647

P37840

Q13627

0

phosphorylation

up-regulates

0.561

In vitro kinase assay of anti-dyrk1a immunocomplexes demonstrated that dyrk1a could phosphorylate alpha-synuclein at ser-87. Furthermore, aggregates formed by phosphorylated alpha-synuclein have a distinct morphology and are more neurotoxic compared with aggregates composed of unmodified wild type alpha-synuclein. These findings suggest alpha-synuclein inclusion formation regulated by dyrk1a, potentially affecting neuronal cell viability.

SIGNOR-149393

P27361

Q01860

1

phosphorylation

down-regulates

0.343

Phosphorylation of this site downregulates nanog, sox2, rex1 and upregulates bmp4, gata6, ddlx5.

SIGNOR-192101

O75581

P45983

0

phosphorylation

up-regulates

0.382

We show that several proline-directed mitogen-activated protein kinases (mapks), such as p38, erk1/2, and jnk1 are sufficient and required for the phosphorylation of ppps/tp motifs of lrp6. External stimuli, which control the activity of mapks, such as phorbol esters and fibroblast growth factor 2 (fgf2) control the choice of the lrp6-ppps/tp kinase and regulate the amplitude of lrp6 phosphorylation and wnt/beta-catenin-dependent transcription.

SIGNOR-169007

Q13131

O15360

1

phosphorylation

up-regulates activity

0.332

FANCA was phosphorylated by AMPK at S347 and phosphorylation increased with MMC treatment. MMC-induced FANCD2 monoubiquitination and nuclear foci formation were compromised in a U2OS cell line that stably overexpressed the S347A mutant form of FANCA compared to wild-type FANCA-overexpressing cells, indicating a requirement for FANCA phosphorylation at S347 for proper activation of the FA/BRCA pathway.

SIGNOR-277264

Q12778

Q9UBE8

0

phosphorylation

down-regulates activity

0.613

Here, we report that the transforming growth factor-beta-activated kinase (TAK1)-Nemo-like kinase (NLK) pathway negatively regulates FOXO1. We show that NLK binds and phosphorylates FOXO1 at Pro-directed Ser/Thr residues in the transactivation domain. The phosphorylation by TAK1-NLK pathway inhibits the transcriptional activity of FOXO1 and excludes FOXO1 from the nucleus, which is independent of phosphatidylinositol 3-kinase/Akt pathway.

SIGNOR-273907

Q04206

Q96EB6

0

deacetylation

down-regulates activity

0.722

SIRT1 physically interacts with the RelA/p65 subunit of NF-kappaB and inhibits transcription by deacetylating RelA/p65 at lysine 310.

SIGNOR-238817

P45984

P12931

1

phosphorylation

up-regulates activity

0.355

Activation of c-Src by JNK2 was accompanied by the phosphorylation of c-Src on threonine residue (s).|JNK2 directly phosphorylates c-Src and activates its auto phosphorylation.

SIGNOR-279221

P31946

Q05655

0

phosphorylation

down-regulates

0.493

We provide a mechanism for these observations through the phosphorylation of 14-3-3 by ikk and pkc on serine residues ser132 and ser60, respectively, which interferes with its binding to ttp and hence the retention of ttp in the cytoplasm.

SIGNOR-138612

P04271

P09630

0

transcriptional regulation

up-regulates quantity by expression

0.2

HOXC6 and HOXC11 increase transcription of S100beta gene in BrdU-induced in vitro differentiation of GOTO neuroblastoma cells into Schwannian cells.

SIGNOR-261646

Q96P20

P45983

0

phosphorylation

up-regulates activity

0.369

Ethanol induced JNK1 phosphorylation activated the NLRP3 inflammasome that induced caspase-1 dependent mitophagy inhibition, thereby exacerbating ROS accumulation and causing cell death.|However, recent studies suggested that Ser 194 phosphorylation of NLRP3 was essential for the control of inflammasome activation and that JNK1 directly phosphorylates NLRP3, which stimulates the self-association and oligomerization of NLRP3 [ xref , xref ].

SIGNOR-280034

Q9UKE5

Q9NQB0

1

phosphorylation

up-regulates

0.555

Here, we report that tnik is an activating kinase for tcf4 and essential for colorectal cancer growth. Tnik, but not its catalytically inactive mutant, phosphorylated the conserved serine 154 residue of tcf4.

SIGNOR-165946

P19544

O00592

1

transcriptional regulation

up-regulates quantity by expression

0.409

Binding of WT1 to conserved elements within the Podocalyxin gene promoter results in potent transcriptional activation, and the specific expression pattern of Podocalyxin in the developing kidney mirrors that of WT1 itself.

SIGNOR-252300

Q15116

Q06124

0

dephosphorylation

down-regulates activity

0.659

Related to the latter notion, we recently showed that SHP2 dephosphorylates PD-1 to disassemble the PD-1:SHP2 complex ( xref ).

SIGNOR-277052

P53779

P30307

1

phosphorylation

down-regulates

0.245

Here we show that jnk directly phosphorylates cdc25c at serine 168 during g(2) phase of the cell cycle. Cdc25c phosphorylation by jnk negatively regulates its phosphatase activity and thereby cdk1 activation, enabling a timely control of mitosis onset.

SIGNOR-164085

P35227

Q03933

1

sumoylation

down-regulates activity

0.325

MEL-18, in contrast to the polycomb protein PC2/CBX4, in which SUMO E3 activity stimulates sumoylation of certain proteins, actually functions like an anti-SUMO E3 protein, interacting with both HSF2 and the SUMO E2 UBC9 but acting to inhibit UBC9 activity and thereby decreasing sumoylation of a target protein, in this case that of HSF2. sumoylation of HSF2 is up-regulated during mitosis and is important for the interaction of this factor with a subunit of the condensin complex during the bookmarking process

SIGNOR-226245

Q92844

O95147

1

ubiquitination

up-regulates activity

0.2

TRAF2-mediated Lys63-linked ubiquitination of DUSP14/MKP6 is essential for its phosphatase activity. Mass spectrometry and mutational analyses identified that DUSP14 was Lys63-linked ubiquitinated at lysine 103 residue.Here we report that DUSP14 was Lys63-linked ubiquitinated at Lys103 residue by the E3 ligase TRAF2 during TCR signaling. Furthermore, ubiquitination of DUSP14 was essential for its phosphatase activity.

SIGNOR-272811