GleghornLab/Signor_2class · Datasets at Hugging Face

IdA string	IdB string	labels int64	mechanism string	effect string	score float64	sentence string	signor_id string
Q16875	O14920	0	phosphorylation	down-regulates activity	0.29	IKKβ promotes metabolic adaptation to glutamine deprivation via phosphorylation and inhibition of PFKFB3.We demonstrate that IKKβ directly interacts with and phosphorylates 6-phosphofructo-2-kinase/fructose-2,6-biphosphatase isoform 3 (PFKFB3), a major driver of aerobic glycolysis, at Ser269 upon glutamine deprivation to inhibit its activity, thereby down-regulating aerobic glycolysis when glutamine levels are low.	SIGNOR-277278
P51813	P40763	1	phosphorylation	up-regulates activity	0.6	BMX activates STAT3 in glioblastoma stem cells.\|BMX has previously been identified as an activator of STAT3, and BMX can phosphorylate STAT3 in vitro.	SIGNOR-279497
P50750	Q9UM73	0	phosphorylation	up-regulates activity	0.296	We report that anaplastic lymphoma kinase (ALK) directly phosphorylates CDK9 at tyrosine-19 to promote homologous recombination (HR) repair and PARP inhibitor resistance. Phospho-CDK9-Tyr19 increases its kinase activity and nuclear localization to stabilize positive transcriptional elongation factor b and activate polymerase II-dependent transcription of HR-repair genes.	SIGNOR-277607
Q96AC1	Q9HCE7	0	ubiquitination	down-regulates quantity by destabilization	0.2	Smurf1 mediates Kindlin-2 proteasomal degradation.\|Smurf1 promotes polyubiquitination of Kindlin-2.	SIGNOR-278614
P27449	Q8N6D2	0	polyubiquitination	down-regulates quantity by destabilization	0.466	The data indicated that RNF182 targeted ATP6V0C for degradation by the ubiquitin-proteosome pathway.	SIGNOR-271771
P06493	Q8WUF5	1	phosphorylation	up-regulates activity	0.505	Cyclin B/cyclin-dependent kinase 1 (CDK1) phosphorylates inhibitor of apoptosis stimulating protein of P53 (iASPP) to promote iASPP nucleus localization and its inhibitory effect on p53.	SIGNOR-273585
Q13131	P31749	0	phosphorylation	down-regulates activity	0.292	It is proposed that the effect of insulin to antagonize AMP-activated protein kinase activation involves a hierarchical mechanism whereby Ser 485/Ser 491 phosphorylation by protein kinase B reduces subsequent phosphorylation of Thr 172 by LKB1 and the resulting activation of AMP-activated protein kinase.	SIGNOR-252739
P01189	P41143	1	chemical activation	up-regulates activity	0.65	Accordingly, for the OTDP, the binding affinity and activity of a large number of opiate compounds have been tested at μ-, δ-, and κ-opiate receptors. Binding studies were originally conducted in guinea pig brain membranes, and subsequent studies have been carried out in CHO cells transfected with human receptors. Table 7 shows a biochemical method for determining activity and potency of opioid compounds, stimulation of [35S]GTPγS binding in membranes from cells transfected with human μ, δ, or κ receptors.	SIGNOR-258409
Q13950	O15297	0	dephosphorylation	up-regulates activity	0.444	Activating dephosphorylation of RUNX2 by Wip1 increases its transcriptional activity on the Bax promoter.	SIGNOR-277110
O60573	Q9Y4X5	0	ubiquitination	down-regulates quantity by destabilization	0.678	Human homologue of Drosophila ariadne (HHARI) is a RING-IBR-RING domain protein identified through its ability to bind the human ubiquitin-conjugating enzyme, UbcH7. Thus, by promoting the ubiquitin-mediated degradation of 4EHP, HHARI may have a role in both protein degradation and protein translation.	SIGNOR-268848
Q9BYG3	P06493	0	phosphorylation	up-regulates activity	0.28	The forkhead-associated (FHA) domain of human Ki67 interacts with the human nucleolar protein hNIFK, recognizing a 44-residue fragment, hNIFK226-269, phosphorylated at Thr234. Here we show that high-affinity binding requires sequential phosphorylation by two kinases, CDK1 and GSK3, yielding pThr238, pThr234 and pSer230. phosphorylation of Thr234 by GSK3 proceeds only after Thr238 is already phosphorylated by CDK1.	SIGNOR-262696
P02671	P22894	0	cleavage	down-regulates quantity by destabilization	0.2	Matrix metalloproteinases collagenase-2, macrophage elastase, collagenase-3, and membrane type 1-matrix metalloproteinase impair clotting by degradation of fibrinogen and factor XII\| We have now investigated the role of collagenase-2 (MMP-8), macrophage elastase (MMP-12), collagenase-3 (MMP-13), and membrane type 1-matrix metalloproteinase (MT1-MMP, MMP-14) in the degradation of fibrinogen and Factor XII of the plasma clotting system. \|Fibrinogen was subjected to MMP-cleavage, and the resulting fragments were isolated. The amino acid sequences were determined by automated Edman degradation.\|MMP-8 20ADSGEGD a-chain \| 442LRTGKEKV a-chain	SIGNOR-263625
P04637	O43819	1	transcriptional regulation	up-regulates quantity by expression	0.64	P53 regulates basal expression of AIF and SCO2 and facilitates oxidative phosphorylation. The expression of GLUT1, GLUT4, and HK2 is negatively regulated by p53, whereas TIGAR expression is induced by p53. The net result of p53-mediated regulation of these glycolytic enzymes is the suppression of glycolysis. In addition, p53 directly binds and inhibits G6PD activity and downregulates the pentose phosphate pathway.	SIGNOR-267463
O00238	O95630	1	phosphorylation	up-regulates activity	0.29	BMP type I receptor activation stimulates AMSH phosphorylation \| The exact position of phosphoserine residues in four phosphopeptides was identified by Edman degradation analysis; spot a for Ser243, Ser245 and Ser247, spot b for Ser2, and spots c and d for Ser48. To confirm the position of the phosphoserine residues, the serine residue(s) in each phosphopeptide was replaced by alanine residues. Then, each mutant as well as wild‐type AMSH was transfected into COS7 cells in the absence or presence of caALK6, and tryptic phosphopeptide mapping of each mutant was performed. As seen in Figure 7, each spot corresponding to the phosphopeptide containing phosphoserine disappeared in the tryptic phosphopeptide mapping. \| Thus, AMSH promotes BMP signaling by negatively regulating the function of I‐Smads.	SIGNOR-250600
P17612	P24588	0	relocalization	up-regulates activity	0.561	In this report, we demonstrate that glutamate receptors and PKA are recruited into a macromolecular signaling complex through direct interaction between the MAGUK proteins, PSD-95 and SAP97, and AKAP79/150	SIGNOR-261292
Q9UGL1	Q16695	1	demethylation	up-regulates activity	0.2	KDM5 subfamily is capable of removing tri‐ and di‐ methyl marks from lysine 4 on histone H3 (H3K4). Depending on the methylation site, its effect on transcription can be either activating or repressing.	SIGNOR-264303
O15055	P04150	0	transcriptional regulation	up-regulates quantity by expression	0.5	GR directly regulates transcription of circadian clock components in mouse and human primary MSCs. Per2, E4bp4, Per1, and Timeless rapidly respond to glucocorticoid stimulation. Primary glucocorticoid receptor (GR) target genes are those at which GR occupies a nearby genomic glucocorticoid response element (GRE) and regulates target gene transcription	SIGNOR-268049
P08138	P22694	0	phosphorylation	up-regulates	0.625	Pka phosphorylates the p75 receptor and regulates its localization to lipid rafts. activation of camp?PKA Is required for translocation of p75ntr to lipid rafts, and for biochemical and biological activities of p75ntr, such as inactivation of rho and the neurite outgrowth.	SIGNOR-99755
O75015	P52738	0	transcriptional regulation	down-regulates quantity by repression	0.2	Thus, these results indicate that these cloned ZNF140 and ZNF91 proteins function as repressors for the human Fc gamma RIIB transcription.	SIGNOR-266214
Q08881	P06239	0	phosphorylation	up-regulates	0.554	Lck phosphorylates the activation loop tyrosine of the Itk kinase domain and activates Itk kinase activity. The major site of Lck phosphorylation on Itk was mapped to the conserved tyrosine (Tyr511) in the activation loop of the Itk kinase domain.	SIGNOR-251380
P19784	Q92915	1	phosphorylation	up-regulates activity	0.307	Bioluminescence-based screening of small molecule modulators of the FGF14:Nav1.6 complex identified 4,5,6,7 -: tetrabromobenzotriazole (TBB), a potent casein kinase 2 (CK2) inhibitor, as a strong suppressor of FGF14:Nav1.6 interaction. Inhibition of CK2 through TBB reduces the interaction of FGF14 with Nav1.6 and Nav1.2 channels. Mass spectrometry confirmed direct phosphorylation of FGF14 by CK2 at S228 and S230, and mutation to alanine at these sites modified FGF14 modulation of Nav1.6-mediated currents.	SIGNOR-275741
Q13309	P46527	1	ubiquitination	down-regulates	0.766	Up-regulation of skp2 by notch signaling enhances proteasome-mediated degradation of the ckis, p27 kip1 and p21 cip1, and causes premature entry into s phase. ;the recognition of p27 by skp2/cks1 of the scfskp2 complex is dictated by cycline/cdk2, providing a high affinity binding site and the phosphorylation of p27 at t187, serving here we provide evidence suggesting that both cdk2/e and phosphorylation of thr(187) on p27 are essential for the recognition of p27 by the scf(skp2/cks1) complex, the ubiquitin-protein isopeptide ligase (e3).	SIGNOR-154194
Q14814	Q9UKX2	1	transcriptional regulation	up-regulates quantity by expression	0.327	Myocyte enhancer factor-2 and serum response factor binding elements regulate fast Myosin heavy chain transcription in vivo. We show that the upstream promoter region of the gene most abundantly expressed in mouse skeletal muscles, IIb MyHC, retains binding activity and transcriptional activation for three positive transcription factors, the serum response factor, Oct-1, and myocyte enhancer factor-2, whereas the other two genes (IIa and IId/x) have nucleotide substitutions in these sites that reduce binding and transcriptional activation	SIGNOR-238712
P23470	P42229	1	dephosphorylation	up-regulates activity	0.265	PTPRG activation by the P1-WD peptide affected the tyrosine phosphorylation of several signaling molecules. Data analysis identified 31 molecules whose phosphorylation was modified in a statistically significant manner (Table I). inhibition of ABL1, BMX, BTK, DAB1, ITGB1, JAK2, KDR, KIT, LIMK1, MET, PDGFRB, SHC1, and VCL correlates with tyrosine dephosphorylation. In contrast, SRC inhibition correlates with hyperphosphorylation of the inhibitory Tyr530 residue and with dephosphorylation of the activatory Tyr419. Moreover, CDK2 and CTTN inhibition correlates with a hyperphosphorylation of the inhibitory Tyr15 and Tyr470, respectively. In contrast, a subgroup of 13 proteins, including BLNK, DOK2, ERBB2, GRIN2B, INSR, PDGFRA, PRKCD, PXN, STAT1, STAT2, STAT3, STAT5A, and ZAP70, appears to be activated by PTPRG activity.	SIGNOR-254730
Q13554	P49840	1	phosphorylation	down-regulates	0.291	Inhibitory phosphorylation of gsk-3 by camkii couples depolarization to neuronal survival.	SIGNOR-167962
Q13627	P78559	1	phosphorylation	up-regulates activity	0.2	The phosphorylation of MAP1A and MAP2 by Dyrk1A was further confirmed by immunoprecipitating these proteins from the soluble fraction obtained after phosphorylating MTs (XREF_FIG).	SIGNOR-279032
P17252	P51674	1	phosphorylation	up-regulates activity	0.324	In summary, a CNS neuron-specific membrane glycoprotein, M6a, could act as a novel NGF-gated Ca2+ channel through the phosphorylation with PKC and augments [Ca2+]i in M6a-S cells.	SIGNOR-263163
P28482	P09874	1	phosphorylation	up-regulates	0.519	Parp1 phosphorylation by erk1/2 is required for maximal parp-1 activation after dna damage. S372a and t373a mutations impaired parp-1 activation.	SIGNOR-146224
Q13309	Q5VWQ8	1	ubiquitination	down-regulates quantity by destabilization	0.267	DAB2IP protein levels can be negatively regulated by the activity of the E3-ubiquitin ligases Fbw7, Skp2, and Smurf1	SIGNOR-254775
P49459	P06493	0	phosphorylation	up-regulates	0.37	Hhr6a is phosphorylated in vitro by cdk-1 and -2 on ser120, a residue conserved in all hhr6a homologues, resulting in a 4-fold increase in its ubiquitin-conjugating activity.	SIGNOR-116504
P49841	P23760	1	phosphorylation	up-regulates quantity	0.334	The ubiquitously expressed CK2 often provides the priming phosphorylation for GSK-3, however, we found that GSK-3beta alone was sufficient to phosphorylate PAX3 at both Ser205 and Ser197 and Ser201 in-vitro.	SIGNOR-278482
O75531	Q8IV63	0	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
P17483	P08833	1	transcriptional regulation	up-regulates quantity by expression	0.2	These data showed that Hox genes selectively activate the transcription of theIGFBP-1	SIGNOR-261636
Q15118	Q16665	0	transcriptional regulation	up-regulates quantity by expression	0.469	Activation of glycolytic genes by HIF-1 is considered critical for metabolic adaptation to hypoxia through increased conversion of glucose to pyruvate and subsequently to lactate. We found that HIF-1 also actively suppresses metabolism through the tricarboxylic acid cycle (TCA) by directly trans-activating the gene encoding pyruvate dehydrogenase kinase 1 (PDK1). PDK1 inactivates the TCA cycle enzyme, pyruvate dehydrogenase (PDH), which converts pyruvate to acetyl-CoA.	SIGNOR-267444
Q13131	Q9H0B6	1	phosphorylation	up-regulates	0.2	Consistent with phosphorylation of both ser545 and ser582 of klc2 contributing to its 14-3-3 binding, a ser545ala mutant of klc2 could be phosphorylated in vitro by ampk on ser582	SIGNOR-174681
O75581	Q9HCP0	0	phosphorylation	up-regulates	0.545	Ck1gamma is associated with lrp6, which has multiple, modular ck1 phosphorylation sites. Wnt treatment induces the rapid ck1gamma-mediated phosphorylation of these sites within lrp6	SIGNOR-143029
Q9ULJ6	P01106	1	transcriptional regulation	up-regulates quantity by expression	0.362	The N-terminal domain (NTD) of Zmiz1 is important for driving Myc transcription and proliferation […] Zmiz1 directly interacted with Notch1 via a tetratricopeptide repeat domain at a special class of Notch-regulatory sites.	SIGNOR-263939
P15336	Q13153	0	phosphorylation	down-regulates activity	0.2	Overall, our results unequivocally confirmed that Pak1 physically interacts with ATF2 and phosphorylates ATF2 on the Ser62 residue, and this process secludes ATF2 in the cytoplasm.	SIGNOR-279377
Q9UKB1	O15534	1	ubiquitination	down-regulates	0.493	We have found that per1 interacts with both _-trcp1 and _-trcp2 in a manner that depends on casein kinase 1 activity, and depletion of both _-trcp1 and _-trcp2 by rnai leads to dramatic stabilization of per1	SIGNOR-137758
Q99717	O43541	1	transcriptional regulation	up-regulates quantity	0.599	Chromatin immunoprecipitation (ChIP) revealed a subset of the BIG (BMP4 induced genes) signature, including Satb2, Smad6, Hand1, Gadd45γ and Gata3, that was bound by Smad1/5 in the developing mandible, revealing direct Smad-mediated regulation	SIGNOR-268940
P62987	Q9BXM7	0	phosphorylation	up-regulates	0.385	Here we report that ubiquitin is the genuine substrate of PINK1. PINK1 phosphorylated ubiquitin at Ser 65 both in vitro and in cells, and a Ser 65 phosphopeptide derived from endogenous ubiquitin was only detected in cells in the presence of PINK1 and following a decrease in mitochondrial membrane potential.	SIGNOR-270342
P53350	Q8N122	1	phosphorylation	up-regulates activity	0.329	Of note, MYC-PLK1 (WT) overexpression strongly enhanced MTOR and RPTOR signals in PLK1 IPs, whereas the LAMP2 signal was strongly decreased (XREF_FIG).\|Thus, we conclude that PLK1 can directly phosphorylate RPTOR in vitro.	SIGNOR-279346
P78356	Q16539	0	phosphorylation	down-regulates	0.2	Inhibition of pip4kbeta activity occurs through the direct phosphorylation of pip4kbeta at ser326 by the p38 stress-activated protein kinase.	SIGNOR-149359
Q13485	Q9Y297	0	ubiquitination	down-regulates	0.388	Here we show that beta-trcp1, a f-box protein in the scf e3 ligase complex, interacts with smad4 and induces the degradation of smad4	SIGNOR-123057
Q9H0H5	P53350	0	phosphorylation	up-regulates	0.638	Tandem mass spectrometry analysis of a purified hscyk-4 fragment (hscyk-4n) phosphorylated by plk1 in vitro identified four major sites (s157, s170, s214, and s260 plk1 phosphorylation of hscyk-4 localizes ect2 at the midzone and stimulates rhoa-dependent contractile ring assembly at the equatorial cortex.	SIGNOR-185758
O14965	P11233	1	phosphorylation	up-regulates activity	0.45	Specifically, the mitotic kinase Aurora A phosphorylates Ser 194 of RALA, relocalizing it to the mitochondria, where it concentrates RALBP1 and DRP1.\|These data suggest that Aurora A promotes mitochondrial fission at mitosis through RalA and RalBP1.	SIGNOR-278351
Q99967	Q14119	0	transcriptional regulation	down-regulates quantity by repression	0.2	The transcription factor Vezf1 represses the expression of the antiangiogenic factor Cited2 in endothelial cells	SIGNOR-266883
Q9P283	Q9H334	0	transcriptional regulation	down-regulates quantity by repression	0.33	FoxP1 stimulates angiogenesis by repressing the inhibitory guidance protein semaphorin 5B in endothelial cells.	SIGNOR-269050
P15336	Q9Y6E7	1	transcriptional regulation	down-regulates quantity by repression	0.2	Our data suggest that mTORC1 promotes the binding of the E3 ligase, βTrCP, to CREB2 (Figure 4D), promoting CREB2 degradation by the proteasome (Figure 4E). Here, we show that mTORC1 promotes glutamine anaplerosis by activating glutamate dehydrogenase (GDH). This regulation requires transcriptional repression of SIRT4, the mitochondrial-localized sirtuin that inhibits GDH. Mechanistically, mTORC1 represses SIRT4 by promoting the proteasome-mediated destabilization of cAMP-responsive element binding 2 (CREB2).	SIGNOR-267831
Q13627	O95644	1	phosphorylation	up-regulates activity	0.429	DYRK1A phosphorylation of NFATc1 and alphaA at S261, S278, S403 and S409 interfered with NFATc1 ubiquitination and ubiquitin-proteasome degradation.\|Here, we demonstrated that DYRK1A increased NFATc1 (NFATc1 and alphaA isoform) protein stability, in contrast to the decrease of NFATc2 protein stability by DYRK1A.	SIGNOR-278278
P04637	Q00536	0	phosphorylation	down-regulates activity	0.386	In this study, we demonstrated that CDK16 phosphorylates p53 at Ser315 and promotes ubiquitination and subsequent degradation of p53.\|Together, these results suggest that CDK16 negatively regulates p53 stability at the post-translational level.	SIGNOR-278354
P48995	Q05655	0	phosphorylation	up-regulates activity	0.2	Taken together, these results indicate that store depletion induces interactions between TRPC1 and PKC\u03b4 in VSMCs, and that these interactions cause PKC\u03b4\u2010dependent phosphorylation of TRPC1.	SIGNOR-279559
Q86YT6	Q16637	1	ubiquitination	down-regulates quantity by destabilization	0.324	The E3 ubiquitin ligase mind bomb 1 ubiquitinates and promotes the degradation of survival of motor neuron protein	SIGNOR-253112
P61073	P34947	0	phosphorylation	down-regulates quantity	0.459	Conversely, GRK5 knock-down in cells with low WIP1 expression inhibited CXCR4 phosphorylation, increased cell membrane expression of CXCR4, and promoted medulloblastoma growth.\|Transfection of GRK5 into D556-WIP1 cells increased Ser339 phosphorylation of CXCR4 and reduced proliferation.	SIGNOR-279740
P49675	P01100	0	transcriptional regulation	up-regulates quantity by expression	0.259	We found that both SF1 and LRH1 can transcriptionally cooperate with the AP-1 family members c-JUN and c-FOS, known to be associated with enhanced proliferation of endometrial carcinoma cells, to further enhance activation of the STAR, HSD3B2, and CYP19A1 PII promoters.	SIGNOR-254878
Q9HCH0	P06493	0	phosphorylation	down-regulates activity	0.2	Inhibiting Cdk1 with purvalanol A in nocodazole arrested cells increased fluorescent intensity of Cep169 at centrosomes relative to the value at the cytosol (2.36 +/- 0.12), while control cells indicated 1.13 +/- 0.03.\|Taken together, these results suggest that the Cdk1-dependent phosphorylation of Cep169 mediates the dissociation from centrosomes during mitosis.	SIGNOR-279144
P16519	P01178	1	cleavage	down-regulates quantity	0.265	Oxytocin-extended form is further cleaved by enzymatic activity to yield the nine-amino-acid active peptide, OT. The proteolysis may involve several pro-hormone convertases, convertase 2 (PC2) (20p11-1-11.2) and convertase 5 (PC5) (9q21.3) (Gabreels et al 1998). Both enzymes are found in OT neurosecretory vesicles and are a part of a family of subtilisen/kexinlike convertases (Seidah et al 1994). It is a product of the OT gene located at human gene locus 20p13 (Rao et al 1992). The processing cascade results in the production of neurophysin I and OT extended form (OT-X), which is OT with a C-terminal, three-amino-acid extension.	SIGNOR-270328
O15111	Q92985	1	phosphorylation	up-regulates	0.688	Ikkalfa associated with and phosphorylated and activate interferon regulatory factor-7 (irf7), which is required for interferon-alfa (ifnalfa) production.	SIGNOR-146116
Q2M1Z3	P61586	1	gtpase-activating protein	down-regulates activity	0.529	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-260488
O43663	P53350	0	phosphorylation	down-regulates activity	0.723	Plk1 negatively regulates PRC1 to prevent premature midzone formation before cytokinesis.\|Plk1, but not Cdk1, phosphorylates PRC1 on Thr-602 to prevent premature midzone assembly in metaphase.	SIGNOR-279645
Q92794	P10147	1	transcriptional regulation	up-regulates quantity by expression	0.2	We further demonstrate that the histone acetyltransferase, MOZ, can activate the MIP-1a promoter in T-cells and that this activation is largely dependent upon the proximal RUNX site. Moreover, we show that co-expression of MOZ and RUNX1 can activate the MIP-1a promoter.	SIGNOR-251726
P53350	Q9H8V3	1	phosphorylation	up-regulates activity	0.75	Phosphorylation of Ect2 by Plk1 during anaphase might alleviate this intramolecular inhibition by dissociating the Ect2 amino from the carboxyl terminus.\|Together with the presence of a prominent microtubule array at the midzone, these data suggest that Plk1 is not essential for the formation of the central spindle at anaphase.The specific failure of Ect2 to localize to the midzone raised the interesting possibility that Plk1 might trigger the initiation of cytokinesis by promoting the interaction of Ect2 with centralspindlin and, thereby, Ect2 activation and recruitment to the central spindle.	SIGNOR-279553
P41594	P17252	0	phosphorylation	up-regulates activity	0.416	Thus, we showed that it is phosphorylation of Ser-839, not Thr-840, that is absolutely required for the unique Ca2+ oscillations produced by mGluR5 activation. The Thr-840 residue is important only in that it is permissive for the PKC-dependent phosphorylation of Ser-839.	SIGNOR-249278
Q9H3Q1	P17252	0	phosphorylation	down-regulates activity	0.2	Cdc42 effector protein-4 (CEP4) was recently identified by our laboratory to be a substrate of multiple PKC isoforms in non-transformed MCF-10A human breast cells. MS/MS analysis verified that Ser(18) and Ser(80) were directly phosphorylated by PKCα in vitro. Phosphorylation of CEP4 severely diminished its affinity for Cdc42 while promoting Rac activation and formation of filopodia (microspikes).	SIGNOR-263160
P27361	P01100	1	phosphorylation	up-regulates activity	0.717	In a previous study we have observed that exposure of nih 3t3 cells to pdgf or serum leads to c-fos phosphorylation by erk on specific residues, thr232, thr325, thr331, and ser374, within the cooh-terminal c-fos tad we have recently shown that erk phosphorylates multiple residues within the carboxylterminal transactivation domain (tad) of c-fos, thus resulting in its increased transcriptional activity.	SIGNOR-118023
O60504	P00519	0	phosphorylation	up-regulates activity	0.412	Abl kinase interacts with and phosphorylates vinexin.	SIGNOR-280172
Q8IZL8	P04150	1	transcriptional regulation	up-regulates quantity by expression	0.553	MNAR functionally interacts with both NH2- and COOH-terminal GR domains to modulate transactivation	SIGNOR-251681
P06241	O14522	1	phosphorylation	down-regulates activity	0.414	Synapse formation by PTPRT was inhibited by phosphorylation of tyrosine 912 within the membrane-proximal catalytic domain of PTPRT by Fyn. This tyrosine phosphorylation reduced phosphatase activity of PTPRT	SIGNOR-275543
Q9UNN5	O14965	0	phosphorylation	down-regulates activity	0.2	This study reports that aurora-a (aur-a) phosphorylates fas-associated factor-1 (faf1) at ser-289 and ser-29 our findings support the negative feedback regulation of aur-a via phosphorylation of the death-promoting protein, faf1	SIGNOR-180891
Q99958	Q00535	0	phosphorylation	up-regulates activity	0.35	Cdk5 phosphorylates Foxc2 and activates Foxc2 dependent transcription.	SIGNOR-279156
P30622	P53350	0	phosphorylation	up-regulates	0.703	Furthermore, we provide evidence that plk1 phosphorylation of clip-170 at s195 enhances its association with ck2	SIGNOR-167172
Q8IXJ9	P42772	1	transcriptional regulation	up-regulates quantity by expression	0.276	Tumor suppressor ASXL1 is essential for the activation of INK4B expression in response to oncogene activity and anti-proliferative signals	SIGNOR-241759
P49768	P55210	0	cleavage	up-regulates activity	0.342	Remarkably, the caspases acting on PS1 could be subdivided in two groups. One group, containing caspase-8, -6 and -11, cleaved PS1 after residues ENDD329 and to a lesser extent after residues AQRD341. A second group consisting of caspase-3, -7 and -1 acted uniquely on AQRD341. Importantly, these two cleavage sites were also recognized by caspases in the C-terminal PS1 fragment produced by constitutive proteolysis.	SIGNOR-261757
O75925	Q12888	1	sumoylation	up-regulates	0.494	Pias1 and pias4 are recruited to dna-damage sites and mediate 53bp1 recruitment and sumoylation.	SIGNOR-162156
P05129	Q99418	1	phosphorylation	down-regulates activity	0.332	ARNO is phosphorylated in vivo by PKC on a single serine residue, S392, located within the carboxy-terminal polybasic domain. Mutation of S392 to alanine does not prevent ARNO-mediated actin rearrangements, suggesting that phosphorylation does not lead to ARNO activation [6]. Here, we report that phosphorylation negatively regulates ARNO exchange activity through a 'PH domain electrostatic switch'.	SIGNOR-249025
P24941	P04150	1	phosphorylation	up-regulates activity	0.291	Cyclin-dependent kinase (CDK) and mitogen-activated protein kinase (MAPK) phosphorylate the rat glucocorticoid receptor in vitro at distinct sites that together correspond to the major phosphorylated receptor residues observed in vivo; MAPK phosphorylates receptor residues threonine 171 and serine 246, whereas multiple CDK complexes modify serines 224 and 232.\|MAPKs and CDKs exert opposite effects on receptor transcriptional enhancement. From our results, we speculate that activators of the MAPK pathway, such as growth factors, insulin, and certain oncoproteins, or inhibitors of CDK function, such as tumor growth factor beta (TGF_), p21, and p27, might attenuate receptor-induced transcrip- tional responses. In contrast, negative regulators of MAPK, such as pKA, as well as activators of CDK, such as the cyclins or CAKs, should potentiate receptor action.	SIGNOR-249427
Q9Y6H5	O43255	0	ubiquitination	down-regulates	0.62	Siah proteins ubiquitylate synphilin-1 and promote its degradation through the ubiquitin proteasome system	SIGNOR-140651
Q8IV61	Q04759	0	phosphorylation	up-regulates	0.328	Activation of rasgrp3 by phosphorylation of thr-133 is required for b cell receptor-mediated ras activation. our data suggest that pkc, after being activated by diacylglycerol, phosphorylates rasgrp3, thereby contributing to its full activation.	SIGNOR-130490
Q9P2Y5	P42345	0	phosphorylation	up-regulates activity	0.408	MTOR phosphorylates UVRAG at serine 550 and serine 571	SIGNOR-276919
P25098	Q00987	0	ubiquitination	down-regulates quantity by destabilization	0.2	Our findings show that the signals enabling activity of the GRK2/MST2/Nek2A axis for separation also switches on Mdm2 degradation of GRK2 to ensure accurate centrosome dynamics and proper mitotic spindle functionality.\|Our results show now that EGF-induced phosphorylation of GRK2 on S670 is a key event in initiating centrosome separation and also a relevant clue for limiting centrosome separation, as this event simultaneously triggers the Mdm2-dependent ubiquitination and degradation of GRK2 ( xref ).	SIGNOR-278629
Q8WYL5	Q9BZL6	0	phosphorylation	down-regulates	0.291	Phosphorylation of ser 402 impedes phosphatase activity of slingshot 1.	SIGNOR-173441
P29376	P29353	1	phosphorylation	up-regulates	0.424	Recently, we demonstrated that ltk utilizes shc and irs-1 as two major substrates and while both equally activate the ras pathway, only irs-1 suppresses apoptosis of hematopoietic cells.	SIGNOR-49625
P31749	O15530	0	phosphorylation	up-regulates	0.748	We have partially purified a kinase from brain extract that phosphorylates Ser473 of PKBalpha in a PtdIns(3,4,5)P3-dependent manner and that is immunoprecipitated with PDK1 antibodies.	SIGNOR-67367
Q15418	P30305	1	phosphorylation	up-regulates	0.253	Rsk promotes g2/m transition through activating phosphorylation of cdc25a and cdc25b rsk is likely to be more active in mitotic cells than in interphase cells, as evidenced by the phosphorylation status of t359/s363 in rsk. Together, these findings indicate that rsk promotes g2/m transition in mammalian cells through activating phosphorylation of cdc25a and cdc25b.	SIGNOR-202125
P17706	P12931	1	dephosphorylation	down-regulates	0.72	We found that tcptp dephosphorylates and inactivates src family kinases to regulate t cell responses._	SIGNOR-177116
Q15797	Q13485	1	phosphorylation	up-regulates	0.671	Whereas alk5 signalling is mediated by phosphorylation of smad2 and smad3 proteins, alk1 signalling is mediated by smad1, smad5, and smad8. Activated smads form a complex with the common(co-Smad; Smad4 in mammals) and shuttle into the nucleus.	SIGNOR-168734
P17612	P21817	1	phosphorylation	up-regulates activity	0.326	PKA-mediated hyperphosphorylation of a conserved serine, Ser-2843 in skeletal RyR and Ser-2809 in cardiac RyR, results in an aberrant SR function during heart failure. hyperphosphorylated RyRs are leaky and therefore lead to a reduced SR Ca2+ load and impaired contractile function in heart failure	SIGNOR-250078
Q7Z434	P17612	0	phosphorylation	down-regulates activity	0.283	Mutagenesis indicated that PKACalpha phosphorylated wild-type VISA and the VISA mutants VISA (S100A), VISA (T234A) and VISA (S238A) but not VISA (T54A) (XREF_FIG, panel C).\|We found that PKACalpha caused degradation of wild-type VISA but not VISA (T54A) or VISA (K7/500R), in which either the PKACs mediated phosphorylation or MARCH5 mediated K48 linked polyubiquitination residues are mutated (XREF_FIG, panel G).	SIGNOR-279649
P40763	Q9Y6X2	0	sumoylation	down-regulates	0.731	Stat3 mediated signaling pathways can be inhibited by pias3 (protein inhibitor of activated stat3), which was recently found to regulate protein stability and function by its sumo (small-ubiquitin like modifiers) ligase activity in promoting sumoylation of important nuclear proteins.	SIGNOR-124723
P27361	Q16204	1	phosphorylation	up-regulates activity	0.367	We have characterized the H4(D10S170) gene product, showing that it is a ubiquitously expressed 55 KDa nuclear and cytosolic protein that is phosphorylated following serum stimulation. This phosphorylation was found to depend on mitogen-activated protein kinase (MAPK) Erk1/2 activity and to be associated to the relocation of H4(D10S170) from the nucleus to the cytosol. S244 is the major target residue of ERK1	SIGNOR-276003
P98177	P48729	0	phosphorylation	down-regulates	0.2	Additionally, ck1, dyrk1a, and cdk2 also phosphorylate foxos at various sites to inhibit foxos activity.	SIGNOR-183664
Q13489	P57078	1	polyubiquitination	up-regulates activity	0.355	CIAP1/2 are direct E3 ligases conjugating diverse types of ubiquitin chains to receptor interacting proteins kinases 1 to 4 (RIP1-4).Together, our results demonstrate that depleting cIAP1/2 inhibits RIP1-4 mediated NF-kB activation without affecting RIP auto-phosphorylation.Lysine residues K51 and K145 of RIP4 are critical for cIAP1-mediated ubiquitination and NF-kB activation.	SIGNOR-272709
P52757	P06239	0	phosphorylation	down-regulates activity	0.2	We now demonstrate Lck-dependent phosphorylation of beta2-chimaerin in response to TCR triggering. We identify Tyr-153 as the Lck-dependent phosphorylation residue and show that its phosphorylation negatively regulates membrane stabilization of beta2-chimaerin, decreasing its GAP activity to Rac.	SIGNOR-276240
O43293	P24844	1	phosphorylation	up-regulates	0.487	More than a dozen kinases have been reported to phosphorylate the rlcs of nm ii (fig. 2), including myosin light chain kinase (mlck;also known as mylk), rho-associated, coiled coil-containing kinase (rock), citron kinase, leucine zipper interacting kinase (zipk;also known as dapk3) and myotonic dystrophy kinase-related cdc42-binding kinase (mrck;also known as cdc42bp)6,34,45,46. These kinases phosphorylate rlcs on ser19, thr18 or both, to relieve the inhibition imposed on the myosin molecule by unphosphorylated rlcs and the head_head interaction outlined above.	SIGNOR-188789
P09629	P09038	1	transcriptional regulation	up-regulates quantity by expression	0.396	Band shift and cotransfection experiments showed that HOXB7 directly transactivates the hFGF gene through one out of five putative homeodomain binding sites present in its promoter.	SIGNOR-261639
O75398	P60763	1	transcriptional regulation	up-regulates quantity by expression	0.2	Affymetrix gene profiling studies revealed Rac3 as a potential target gene and quantitative RT-PCR analysis confirmed that Rac3 was upregulated by Deaf-1 in immortalized mouse mammary epithelial cells.	SIGNOR-269059
P46934	P60321	1	ubiquitination	down-regulates quantity by destabilization	0.2	We find that NEDD4 targets an RNA-binding protein, NANOS2, in spermatogonia to destabilize it, leading to cell differentiation.\|To examine whether complex formation of NEDD4 and NDFIP2 promotes NANOS2 ubiquitination in vivo, FLAG tagged NANOS2 was expressed in HEK293 cells with or without MYC-NEDD4 and MYC-NDFIP2.	SIGNOR-278770
Q2TAL8	Q9BW92	1	transcriptional regulation	up-regulates quantity by expression	0.2	QRICH1 promotes the expression of translation-related genes. our combined ChIP-seq and RNA-seq analyses identified that QRICH1 and ATF4 were enriched at the promoters of these specific tRNA synthetases, and that ER stress positively regulated their transcription (Fig. 4I). Together, these findings suggest that QRICH1 and ATF4 modulate tRNA metabolic processes to promote secreted protein synthesis during ER stress.	SIGNOR-269407
Q99717	P36894	0	phosphorylation	up-regulates activity	0.688	Two types of bmp-induced signaling pathways are known, the smad and p38 mapk pathways. In the former case, bmpr1 phosphorylates smad-1,-5,-8, which forms a complex with smad4 that translocates into the nucleus and regulates gene expression.	SIGNOR-255261
P49841	P49715	1	phosphorylation	up-regulates activity	0.379	Glycogen synthase kinase 3 (GSK3) phosphorylates T222 and T226, causing a conformational change in C/EBPα. GSK3-mediated phosphorylation does not, in itself, dramatically alter the activity of C/EBPα in our assays. phosphorylation of C/EBPalpha and other substrates by GSK3 may be required for adipogenesis, since treatment of differentiating preadipocytes with lithium inhibits their conversion to adipocytes.	SIGNOR-251231

Q16875

O14920

0

phosphorylation

down-regulates activity

0.29

IKKβ promotes metabolic adaptation to glutamine deprivation via phosphorylation and inhibition of PFKFB3.We demonstrate that IKKβ directly interacts with and phosphorylates 6-phosphofructo-2-kinase/fructose-2,6-biphosphatase isoform 3 (PFKFB3), a major driver of aerobic glycolysis, at Ser269 upon glutamine deprivation to inhibit its activity, thereby down-regulating aerobic glycolysis when glutamine levels are low.

SIGNOR-277278

P51813

P40763

1

phosphorylation

up-regulates activity

0.6

BMX activates STAT3 in glioblastoma stem cells.|BMX has previously been identified as an activator of STAT3, and BMX can phosphorylate STAT3 in vitro.

SIGNOR-279497

P50750

Q9UM73

0

phosphorylation

up-regulates activity

0.296

We report that anaplastic lymphoma kinase (ALK) directly phosphorylates CDK9 at tyrosine-19 to promote homologous recombination (HR) repair and PARP inhibitor resistance. Phospho-CDK9-Tyr19 increases its kinase activity and nuclear localization to stabilize positive transcriptional elongation factor b and activate polymerase II-dependent transcription of HR-repair genes.

SIGNOR-277607

Q96AC1

Q9HCE7

0

ubiquitination

down-regulates quantity by destabilization

0.2

Smurf1 mediates Kindlin-2 proteasomal degradation.|Smurf1 promotes polyubiquitination of Kindlin-2.

SIGNOR-278614

P27449

Q8N6D2

0

polyubiquitination

down-regulates quantity by destabilization

0.466

The data indicated that RNF182 targeted ATP6V0C for degradation by the ubiquitin-proteosome pathway.

SIGNOR-271771

P06493

Q8WUF5

1

phosphorylation

up-regulates activity

0.505

Cyclin B/cyclin-dependent kinase 1 (CDK1) phosphorylates inhibitor of apoptosis stimulating protein of P53 (iASPP) to promote iASPP nucleus localization and its inhibitory effect on p53.

SIGNOR-273585

Q13131

P31749

0

phosphorylation

down-regulates activity

0.292

It is proposed that the effect of insulin to antagonize AMP-activated protein kinase activation involves a hierarchical mechanism whereby Ser 485/Ser 491 phosphorylation by protein kinase B reduces subsequent phosphorylation of Thr 172 by LKB1 and the resulting activation of AMP-activated protein kinase.

SIGNOR-252739

P01189

P41143

1

chemical activation

up-regulates activity

0.65

Accordingly, for the OTDP, the binding affinity and activity of a large number of opiate compounds have been tested at μ-, δ-, and κ-opiate receptors. Binding studies were originally conducted in guinea pig brain membranes, and subsequent studies have been carried out in CHO cells transfected with human receptors. Table 7 shows a biochemical method for determining activity and potency of opioid compounds, stimulation of [35S]GTPγS binding in membranes from cells transfected with human μ, δ, or κ receptors.

SIGNOR-258409

Q13950

O15297

0

dephosphorylation

up-regulates activity

0.444

Activating dephosphorylation of RUNX2 by Wip1 increases its transcriptional activity on the Bax promoter.

SIGNOR-277110

O60573

Q9Y4X5

0

ubiquitination

down-regulates quantity by destabilization

0.678

Human homologue of Drosophila ariadne (HHARI) is a RING-IBR-RING domain protein identified through its ability to bind the human ubiquitin-conjugating enzyme, UbcH7. Thus, by promoting the ubiquitin-mediated degradation of 4EHP, HHARI may have a role in both protein degradation and protein translation.

SIGNOR-268848

Q9BYG3

P06493

0

phosphorylation

up-regulates activity

0.28

The forkhead-associated (FHA) domain of human Ki67 interacts with the human nucleolar protein hNIFK, recognizing a 44-residue fragment, hNIFK226-269, phosphorylated at Thr234. Here we show that high-affinity binding requires sequential phosphorylation by two kinases, CDK1 and GSK3, yielding pThr238, pThr234 and pSer230. phosphorylation of Thr234 by GSK3 proceeds only after Thr238 is already phosphorylated by CDK1.

SIGNOR-262696

P02671

P22894

0

cleavage

down-regulates quantity by destabilization

0.2

Matrix metalloproteinases collagenase-2, macrophage elastase, collagenase-3, and membrane type 1-matrix metalloproteinase impair clotting by degradation of fibrinogen and factor XII| We have now investigated the role of collagenase-2 (MMP-8), macrophage elastase (MMP-12), collagenase-3 (MMP-13), and membrane type 1-matrix metalloproteinase (MT1-MMP, MMP-14) in the degradation of fibrinogen and Factor XII of the plasma clotting system. |Fibrinogen was subjected to MMP-cleavage, and the resulting fragments were isolated. The amino acid sequences were determined by automated Edman degradation.|MMP-8 20ADSGEGD a-chain | 442LRTGKEKV a-chain

SIGNOR-263625

P04637

O43819

1

transcriptional regulation

up-regulates quantity by expression

0.64

P53 regulates basal expression of AIF and SCO2 and facilitates oxidative phosphorylation. The expression of GLUT1, GLUT4, and HK2 is negatively regulated by p53, whereas TIGAR expression is induced by p53. The net result of p53-mediated regulation of these glycolytic enzymes is the suppression of glycolysis. In addition, p53 directly binds and inhibits G6PD activity and downregulates the pentose phosphate pathway.

SIGNOR-267463

O00238

O95630

1

phosphorylation

up-regulates activity

0.29

BMP type I receptor activation stimulates AMSH phosphorylation | The exact position of phosphoserine residues in four phosphopeptides was identified by Edman degradation analysis; spot a for Ser243, Ser245 and Ser247, spot b for Ser2, and spots c and d for Ser48. To confirm the position of the phosphoserine residues, the serine residue(s) in each phosphopeptide was replaced by alanine residues. Then, each mutant as well as wild‐type AMSH was transfected into COS7 cells in the absence or presence of caALK6, and tryptic phosphopeptide mapping of each mutant was performed. As seen in Figure 7, each spot corresponding to the phosphopeptide containing phosphoserine disappeared in the tryptic phosphopeptide mapping. | Thus, AMSH promotes BMP signaling by negatively regulating the function of I‐Smads.

SIGNOR-250600

P17612

P24588

0

relocalization

up-regulates activity

0.561

In this report, we demonstrate that glutamate receptors and PKA are recruited into a macromolecular signaling complex through direct interaction between the MAGUK proteins, PSD-95 and SAP97, and AKAP79/150

SIGNOR-261292

Q9UGL1

Q16695

1

demethylation

up-regulates activity

0.2

KDM5 subfamily is capable of removing tri‐ and di‐ methyl marks from lysine 4 on histone H3 (H3K4). Depending on the methylation site, its effect on transcription can be either activating or repressing.

SIGNOR-264303

O15055

P04150

0

transcriptional regulation

up-regulates quantity by expression

0.5

GR directly regulates transcription of circadian clock components in mouse and human primary MSCs. Per2, E4bp4, Per1, and Timeless rapidly respond to glucocorticoid stimulation. Primary glucocorticoid receptor (GR) target genes are those at which GR occupies a nearby genomic glucocorticoid response element (GRE) and regulates target gene transcription

SIGNOR-268049

P08138

P22694

0

phosphorylation

up-regulates

0.625

Pka phosphorylates the p75 receptor and regulates its localization to lipid rafts. activation of camp?PKA Is required for translocation of p75ntr to lipid rafts, and for biochemical and biological activities of p75ntr, such as inactivation of rho and the neurite outgrowth.

SIGNOR-99755

O75015

P52738

0

transcriptional regulation

down-regulates quantity by repression

0.2

Thus, these results indicate that these cloned ZNF140 and ZNF91 proteins function as repressors for the human Fc gamma RIIB transcription.

SIGNOR-266214

Q08881

P06239

0

phosphorylation

up-regulates

0.554

Lck phosphorylates the activation loop tyrosine of the Itk kinase domain and activates Itk kinase activity. The major site of Lck phosphorylation on Itk was mapped to the conserved tyrosine (Tyr511) in the activation loop of the Itk kinase domain.

SIGNOR-251380

P19784

Q92915

1

phosphorylation

up-regulates activity

0.307

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

SIGNOR-275741

Q13309

P46527

1

ubiquitination

down-regulates

0.766

Up-regulation of skp2 by notch signaling enhances proteasome-mediated degradation of the ckis, p27 kip1 and p21 cip1, and causes premature entry into s phase. ;the recognition of p27 by skp2/cks1 of the scfskp2 complex is dictated by cycline/cdk2, providing a high affinity binding site and the phosphorylation of p27 at t187, serving here we provide evidence suggesting that both cdk2/e and phosphorylation of thr(187) on p27 are essential for the recognition of p27 by the scf(skp2/cks1) complex, the ubiquitin-protein isopeptide ligase (e3).

SIGNOR-154194

Q14814

Q9UKX2

1

transcriptional regulation

up-regulates quantity by expression

0.327

Myocyte enhancer factor-2 and serum response factor binding elements regulate fast Myosin heavy chain transcription in vivo. We show that the upstream promoter region of the gene most abundantly expressed in mouse skeletal muscles, IIb MyHC, retains binding activity and transcriptional activation for three positive transcription factors, the serum response factor, Oct-1, and myocyte enhancer factor-2, whereas the other two genes (IIa and IId/x) have nucleotide substitutions in these sites that reduce binding and transcriptional activation

SIGNOR-238712

P23470

P42229

1

dephosphorylation

up-regulates activity

0.265

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

SIGNOR-254730

Q13554

P49840

1

phosphorylation

down-regulates

0.291

Inhibitory phosphorylation of gsk-3 by camkii couples depolarization to neuronal survival.

SIGNOR-167962

Q13627

P78559

1

phosphorylation

up-regulates activity

0.2

The phosphorylation of MAP1A and MAP2 by Dyrk1A was further confirmed by immunoprecipitating these proteins from the soluble fraction obtained after phosphorylating MTs (XREF_FIG).

SIGNOR-279032

P17252

P51674

1

phosphorylation

up-regulates activity

0.324

In summary, a CNS neuron-specific membrane glycoprotein, M6a, could act as a novel NGF-gated Ca2+ channel through the phosphorylation with PKC and augments [Ca2+]i in M6a-S cells.

SIGNOR-263163

P28482

P09874

1

phosphorylation

up-regulates

0.519

Parp1 phosphorylation by erk1/2 is required for maximal parp-1 activation after dna damage. S372a and t373a mutations impaired parp-1 activation.

SIGNOR-146224

Q13309

Q5VWQ8

1

ubiquitination

down-regulates quantity by destabilization

0.267

DAB2IP protein levels can be negatively regulated by the activity of the E3-ubiquitin ligases Fbw7, Skp2, and Smurf1

SIGNOR-254775

P49459

P06493

0

phosphorylation

up-regulates

0.37

Hhr6a is phosphorylated in vitro by cdk-1 and -2 on ser120, a residue conserved in all hhr6a homologues, resulting in a 4-fold increase in its ubiquitin-conjugating activity.

SIGNOR-116504

P49841

P23760

1

phosphorylation

up-regulates quantity

0.334

The ubiquitously expressed CK2 often provides the priming phosphorylation for GSK-3, however, we found that GSK-3beta alone was sufficient to phosphorylate PAX3 at both Ser205 and Ser197 and Ser201 in-vitro.

SIGNOR-278482

O75531

Q8IV63

0

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

P17483

P08833

1

transcriptional regulation

up-regulates quantity by expression

0.2

These data showed that Hox genes selectively activate the transcription of theIGFBP-1

SIGNOR-261636

Q15118

Q16665

0

transcriptional regulation

up-regulates quantity by expression

0.469

Activation of glycolytic genes by HIF-1 is considered critical for metabolic adaptation to hypoxia through increased conversion of glucose to pyruvate and subsequently to lactate. We found that HIF-1 also actively suppresses metabolism through the tricarboxylic acid cycle (TCA) by directly trans-activating the gene encoding pyruvate dehydrogenase kinase 1 (PDK1). PDK1 inactivates the TCA cycle enzyme, pyruvate dehydrogenase (PDH), which converts pyruvate to acetyl-CoA.

SIGNOR-267444

Q13131

Q9H0B6

1

phosphorylation

up-regulates

0.2

Consistent with phosphorylation of both ser545 and ser582 of klc2 contributing to its 14-3-3 binding, a ser545ala mutant of klc2 could be phosphorylated in vitro by ampk on ser582

SIGNOR-174681

O75581

Q9HCP0

0

phosphorylation

up-regulates

0.545

Ck1gamma is associated with lrp6, which has multiple, modular ck1 phosphorylation sites. Wnt treatment induces the rapid ck1gamma-mediated phosphorylation of these sites within lrp6

SIGNOR-143029

Q9ULJ6

P01106

1

transcriptional regulation

up-regulates quantity by expression

0.362

The N-terminal domain (NTD) of Zmiz1 is important for driving Myc transcription and proliferation […] Zmiz1 directly interacted with Notch1 via a tetratricopeptide repeat domain at a special class of Notch-regulatory sites.

SIGNOR-263939

P15336

Q13153

0

phosphorylation

down-regulates activity

0.2

Overall, our results unequivocally confirmed that Pak1 physically interacts with ATF2 and phosphorylates ATF2 on the Ser62 residue, and this process secludes ATF2 in the cytoplasm.

SIGNOR-279377

Q9UKB1

O15534

1

ubiquitination

down-regulates

0.493

We have found that per1 interacts with both _-trcp1 and _-trcp2 in a manner that depends on casein kinase 1 activity, and depletion of both _-trcp1 and _-trcp2 by rnai leads to dramatic stabilization of per1

SIGNOR-137758

Q99717

O43541

1

transcriptional regulation

up-regulates quantity

0.599

Chromatin immunoprecipitation (ChIP) revealed a subset of the BIG (BMP4 induced genes) signature, including Satb2, Smad6, Hand1, Gadd45γ and Gata3, that was bound by Smad1/5 in the developing mandible, revealing direct Smad-mediated regulation

SIGNOR-268940

P62987

Q9BXM7

0

phosphorylation

up-regulates

0.385

Here we report that ubiquitin is the genuine substrate of PINK1. PINK1 phosphorylated ubiquitin at Ser 65 both in vitro and in cells, and a Ser 65 phosphopeptide derived from endogenous ubiquitin was only detected in cells in the presence of PINK1 and following a decrease in mitochondrial membrane potential.

SIGNOR-270342

P53350

Q8N122

1

phosphorylation

up-regulates activity

0.329

Of note, MYC-PLK1 (WT) overexpression strongly enhanced MTOR and RPTOR signals in PLK1 IPs, whereas the LAMP2 signal was strongly decreased (XREF_FIG).|Thus, we conclude that PLK1 can directly phosphorylate RPTOR in vitro.

SIGNOR-279346

P78356

Q16539

0

phosphorylation

down-regulates

0.2

Inhibition of pip4kbeta activity occurs through the direct phosphorylation of pip4kbeta at ser326 by the p38 stress-activated protein kinase.

SIGNOR-149359

Q13485

Q9Y297

0

ubiquitination

down-regulates

0.388

Here we show that beta-trcp1, a f-box protein in the scf e3 ligase complex, interacts with smad4 and induces the degradation of smad4

SIGNOR-123057

Q9H0H5

P53350

0

phosphorylation

up-regulates

0.638

Tandem mass spectrometry analysis of a purified hscyk-4 fragment (hscyk-4n) phosphorylated by plk1 in vitro identified four major sites (s157, s170, s214, and s260 plk1 phosphorylation of hscyk-4 localizes ect2 at the midzone and stimulates rhoa-dependent contractile ring assembly at the equatorial cortex.

SIGNOR-185758

O14965

P11233

1

phosphorylation

up-regulates activity

0.45

Specifically, the mitotic kinase Aurora A phosphorylates Ser 194 of RALA, relocalizing it to the mitochondria, where it concentrates RALBP1 and DRP1.|These data suggest that Aurora A promotes mitochondrial fission at mitosis through RalA and RalBP1.

SIGNOR-278351

Q99967

Q14119

0

transcriptional regulation

down-regulates quantity by repression

0.2

The transcription factor Vezf1 represses the expression of the antiangiogenic factor Cited2 in endothelial cells

SIGNOR-266883

Q9P283

Q9H334

0

transcriptional regulation

down-regulates quantity by repression

0.33

FoxP1 stimulates angiogenesis by repressing the inhibitory guidance protein semaphorin 5B in endothelial cells.

SIGNOR-269050

P15336

Q9Y6E7

1

transcriptional regulation

down-regulates quantity by repression

0.2

Our data suggest that mTORC1 promotes the binding of the E3 ligase, βTrCP, to CREB2 (Figure 4D), promoting CREB2 degradation by the proteasome (Figure 4E). Here, we show that mTORC1 promotes glutamine anaplerosis by activating glutamate dehydrogenase (GDH). This regulation requires transcriptional repression of SIRT4, the mitochondrial-localized sirtuin that inhibits GDH. Mechanistically, mTORC1 represses SIRT4 by promoting the proteasome-mediated destabilization of cAMP-responsive element binding 2 (CREB2).

SIGNOR-267831

Q13627

O95644

1

phosphorylation

up-regulates activity

0.429

DYRK1A phosphorylation of NFATc1 and alphaA at S261, S278, S403 and S409 interfered with NFATc1 ubiquitination and ubiquitin-proteasome degradation.|Here, we demonstrated that DYRK1A increased NFATc1 (NFATc1 and alphaA isoform) protein stability, in contrast to the decrease of NFATc2 protein stability by DYRK1A.

SIGNOR-278278

P04637

Q00536

0

phosphorylation

down-regulates activity

0.386

In this study, we demonstrated that CDK16 phosphorylates p53 at Ser315 and promotes ubiquitination and subsequent degradation of p53.|Together, these results suggest that CDK16 negatively regulates p53 stability at the post-translational level.

SIGNOR-278354

P48995

Q05655

0

phosphorylation

up-regulates activity

0.2

Taken together, these results indicate that store depletion induces interactions between TRPC1 and PKC\u03b4 in VSMCs, and that these interactions cause PKC\u03b4\u2010dependent phosphorylation of TRPC1.

SIGNOR-279559

Q86YT6

Q16637

1

ubiquitination

down-regulates quantity by destabilization

0.324

The E3 ubiquitin ligase mind bomb 1 ubiquitinates and promotes the degradation of survival of motor neuron protein

SIGNOR-253112

P61073

P34947

0

phosphorylation

down-regulates quantity

0.459

Conversely, GRK5 knock-down in cells with low WIP1 expression inhibited CXCR4 phosphorylation, increased cell membrane expression of CXCR4, and promoted medulloblastoma growth.|Transfection of GRK5 into D556-WIP1 cells increased Ser339 phosphorylation of CXCR4 and reduced proliferation.

SIGNOR-279740

P49675

P01100

0

transcriptional regulation

up-regulates quantity by expression

0.259

We found that both SF1 and LRH1 can transcriptionally cooperate with the AP-1 family members c-JUN and c-FOS, known to be associated with enhanced proliferation of endometrial carcinoma cells, to further enhance activation of the STAR, HSD3B2, and CYP19A1 PII promoters.

SIGNOR-254878

Q9HCH0

P06493

0

phosphorylation

down-regulates activity

0.2

Inhibiting Cdk1 with purvalanol A in nocodazole arrested cells increased fluorescent intensity of Cep169 at centrosomes relative to the value at the cytosol (2.36 +/- 0.12), while control cells indicated 1.13 +/- 0.03.|Taken together, these results suggest that the Cdk1-dependent phosphorylation of Cep169 mediates the dissociation from centrosomes during mitosis.

SIGNOR-279144

P16519

P01178

1

cleavage

down-regulates quantity

0.265

Oxytocin-extended form is further cleaved by enzymatic activity to yield the nine-amino-acid active peptide, OT. The proteolysis may involve several pro-hormone convertases, convertase 2 (PC2) (20p11-1-11.2) and convertase 5 (PC5) (9q21.3) (Gabreels et al 1998). Both enzymes are found in OT neurosecretory vesicles and are a part of a family of subtilisen/kexinlike convertases (Seidah et al 1994). It is a product of the OT gene located at human gene locus 20p13 (Rao et al 1992). The processing cascade results in the production of neurophysin I and OT extended form (OT-X), which is OT with a C-terminal, three-amino-acid extension.

SIGNOR-270328

O15111

Q92985

1

phosphorylation

up-regulates

0.688

Ikkalfa associated with and phosphorylated and activate interferon regulatory factor-7 (irf7), which is required for interferon-alfa (ifnalfa) production.

SIGNOR-146116

Q2M1Z3

P61586

1

gtpase-activating protein

down-regulates activity

0.529

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-260488

O43663

P53350

0

phosphorylation

down-regulates activity

0.723

Plk1 negatively regulates PRC1 to prevent premature midzone formation before cytokinesis.|Plk1, but not Cdk1, phosphorylates PRC1 on Thr-602 to prevent premature midzone assembly in metaphase.

SIGNOR-279645

Q92794

P10147

1

transcriptional regulation

up-regulates quantity by expression

0.2

We further demonstrate that the histone acetyltransferase, MOZ, can activate the MIP-1a promoter in T-cells and that this activation is largely dependent upon the proximal RUNX site. Moreover, we show that co-expression of MOZ and RUNX1 can activate the MIP-1a promoter.

SIGNOR-251726

P53350

Q9H8V3

1

phosphorylation

up-regulates activity

0.75

Phosphorylation of Ect2 by Plk1 during anaphase might alleviate this intramolecular inhibition by dissociating the Ect2 amino from the carboxyl terminus.|Together with the presence of a prominent microtubule array at the midzone, these data suggest that Plk1 is not essential for the formation of the central spindle at anaphase.The specific failure of Ect2 to localize to the midzone raised the interesting possibility that Plk1 might trigger the initiation of cytokinesis by promoting the interaction of Ect2 with centralspindlin and, thereby, Ect2 activation and recruitment to the central spindle.

SIGNOR-279553

P41594

P17252

0

phosphorylation

up-regulates activity

0.416

Thus, we showed that it is phosphorylation of Ser-839, not Thr-840, that is absolutely required for the unique Ca2+ oscillations produced by mGluR5 activation. The Thr-840 residue is important only in that it is permissive for the PKC-dependent phosphorylation of Ser-839.

SIGNOR-249278

Q9H3Q1

P17252

0

phosphorylation

down-regulates activity

0.2

Cdc42 effector protein-4 (CEP4) was recently identified by our laboratory to be a substrate of multiple PKC isoforms in non-transformed MCF-10A human breast cells. MS/MS analysis verified that Ser(18) and Ser(80) were directly phosphorylated by PKCα in vitro. Phosphorylation of CEP4 severely diminished its affinity for Cdc42 while promoting Rac activation and formation of filopodia (microspikes).

SIGNOR-263160

P27361

P01100

1

phosphorylation

up-regulates activity

0.717

In a previous study we have observed that exposure of nih 3t3 cells to pdgf or serum leads to c-fos phosphorylation by erk on specific residues, thr232, thr325, thr331, and ser374, within the cooh-terminal c-fos tad we have recently shown that erk phosphorylates multiple residues within the carboxylterminal transactivation domain (tad) of c-fos, thus resulting in its increased transcriptional activity.

SIGNOR-118023

O60504

P00519

0

phosphorylation

up-regulates activity

0.412

Abl kinase interacts with and phosphorylates vinexin.

SIGNOR-280172

Q8IZL8

P04150

1

transcriptional regulation

up-regulates quantity by expression

0.553

MNAR functionally interacts with both NH2- and COOH-terminal GR domains to modulate transactivation

SIGNOR-251681

P06241

O14522

1

phosphorylation

down-regulates activity

0.414

Synapse formation by PTPRT was inhibited by phosphorylation of tyrosine 912 within the membrane-proximal catalytic domain of PTPRT by Fyn. This tyrosine phosphorylation reduced phosphatase activity of PTPRT

SIGNOR-275543

Q9UNN5

O14965

0

phosphorylation

down-regulates activity

0.2

This study reports that aurora-a (aur-a) phosphorylates fas-associated factor-1 (faf1) at ser-289 and ser-29 our findings support the negative feedback regulation of aur-a via phosphorylation of the death-promoting protein, faf1

SIGNOR-180891

Q99958

Q00535

0

phosphorylation

up-regulates activity

0.35

Cdk5 phosphorylates Foxc2 and activates Foxc2 dependent transcription.

SIGNOR-279156

P30622

P53350

0

phosphorylation

up-regulates

0.703

Furthermore, we provide evidence that plk1 phosphorylation of clip-170 at s195 enhances its association with ck2

SIGNOR-167172

Q8IXJ9

P42772

1

transcriptional regulation

up-regulates quantity by expression

0.276

Tumor suppressor ASXL1 is essential for the activation of INK4B expression in response to oncogene activity and anti-proliferative signals

SIGNOR-241759

P49768

P55210

0

cleavage

up-regulates activity

0.342

Remarkably, the caspases acting on PS1 could be subdivided in two groups. One group, containing caspase-8, -6 and -11, cleaved PS1 after residues ENDD329 and to a lesser extent after residues AQRD341. A second group consisting of caspase-3, -7 and -1 acted uniquely on AQRD341. Importantly, these two cleavage sites were also recognized by caspases in the C-terminal PS1 fragment produced by constitutive proteolysis.

SIGNOR-261757

O75925

Q12888

1

sumoylation

up-regulates

0.494

Pias1 and pias4 are recruited to dna-damage sites and mediate 53bp1 recruitment and sumoylation.

SIGNOR-162156

P05129

Q99418

1

phosphorylation

down-regulates activity

0.332

ARNO is phosphorylated in vivo by PKC on a single serine residue, S392, located within the carboxy-terminal polybasic domain. Mutation of S392 to alanine does not prevent ARNO-mediated actin rearrangements, suggesting that phosphorylation does not lead to ARNO activation [6]. Here, we report that phosphorylation negatively regulates ARNO exchange activity through a 'PH domain electrostatic switch'.

SIGNOR-249025

P24941

P04150

1

phosphorylation

up-regulates activity

0.291

Cyclin-dependent kinase (CDK) and mitogen-activated protein kinase (MAPK) phosphorylate the rat glucocorticoid receptor in vitro at distinct sites that together correspond to the major phosphorylated receptor residues observed in vivo; MAPK phosphorylates receptor residues threonine 171 and serine 246, whereas multiple CDK complexes modify serines 224 and 232.|MAPKs and CDKs exert opposite effects on receptor transcriptional enhancement. From our results, we speculate that activators of the MAPK pathway, such as growth factors, insulin, and certain oncoproteins, or inhibitors of CDK function, such as tumor growth factor beta (TGF_), p21, and p27, might attenuate receptor-induced transcrip- tional responses. In contrast, negative regulators of MAPK, such as pKA, as well as activators of CDK, such as the cyclins or CAKs, should potentiate receptor action.

SIGNOR-249427

Q9Y6H5

O43255

0

ubiquitination

down-regulates

0.62

Siah proteins ubiquitylate synphilin-1 and promote its degradation through the ubiquitin proteasome system

SIGNOR-140651

Q8IV61

Q04759

0

phosphorylation

up-regulates

0.328

Activation of rasgrp3 by phosphorylation of thr-133 is required for b cell receptor-mediated ras activation. our data suggest that pkc, after being activated by diacylglycerol, phosphorylates rasgrp3, thereby contributing to its full activation.

SIGNOR-130490

Q9P2Y5

P42345

0

phosphorylation

up-regulates activity

0.408

MTOR phosphorylates UVRAG at serine 550 and serine 571

SIGNOR-276919

P25098

Q00987

0

ubiquitination

down-regulates quantity by destabilization

0.2

Our findings show that the signals enabling activity of the GRK2/MST2/Nek2A axis for separation also switches on Mdm2 degradation of GRK2 to ensure accurate centrosome dynamics and proper mitotic spindle functionality.|Our results show now that EGF-induced phosphorylation of GRK2 on S670 is a key event in initiating centrosome separation and also a relevant clue for limiting centrosome separation, as this event simultaneously triggers the Mdm2-dependent ubiquitination and degradation of GRK2 ( xref ).

SIGNOR-278629

Q8WYL5

Q9BZL6

0

phosphorylation

down-regulates

0.291

Phosphorylation of ser 402 impedes phosphatase activity of slingshot 1.

SIGNOR-173441

P29376

P29353

1

phosphorylation

up-regulates

0.424

Recently, we demonstrated that ltk utilizes shc and irs-1 as two major substrates and while both equally activate the ras pathway, only irs-1 suppresses apoptosis of hematopoietic cells.

SIGNOR-49625

P31749

O15530

0

phosphorylation

up-regulates

0.748

We have partially purified a kinase from brain extract that phosphorylates Ser473 of PKBalpha in a PtdIns(3,4,5)P3-dependent manner and that is immunoprecipitated with PDK1 antibodies.

SIGNOR-67367

Q15418

P30305

1

phosphorylation

up-regulates

0.253

Rsk promotes g2/m transition through activating phosphorylation of cdc25a and cdc25b rsk is likely to be more active in mitotic cells than in interphase cells, as evidenced by the phosphorylation status of t359/s363 in rsk. Together, these findings indicate that rsk promotes g2/m transition in mammalian cells through activating phosphorylation of cdc25a and cdc25b.

SIGNOR-202125

P17706

P12931

1

dephosphorylation

down-regulates

0.72

We found that tcptp dephosphorylates and inactivates src family kinases to regulate t cell responses._

SIGNOR-177116

Q15797

Q13485

1

phosphorylation

up-regulates

0.671

Whereas alk5 signalling is mediated by phosphorylation of smad2 and smad3 proteins, alk1 signalling is mediated by smad1, smad5, and smad8. Activated smads form a complex with the common(co-Smad; Smad4 in mammals) and shuttle into the nucleus.

SIGNOR-168734

P17612

P21817

1

phosphorylation

up-regulates activity

0.326

PKA-mediated hyperphosphorylation of a conserved serine, Ser-2843 in skeletal RyR and Ser-2809 in cardiac RyR, results in an aberrant SR function during heart failure. hyperphosphorylated RyRs are leaky and therefore lead to a reduced SR Ca2+ load and impaired contractile function in heart failure

SIGNOR-250078

Q7Z434

P17612

0

phosphorylation

down-regulates activity

0.283

Mutagenesis indicated that PKACalpha phosphorylated wild-type VISA and the VISA mutants VISA (S100A), VISA (T234A) and VISA (S238A) but not VISA (T54A) (XREF_FIG, panel C).|We found that PKACalpha caused degradation of wild-type VISA but not VISA (T54A) or VISA (K7/500R), in which either the PKACs mediated phosphorylation or MARCH5 mediated K48 linked polyubiquitination residues are mutated (XREF_FIG, panel G).

SIGNOR-279649

P40763

Q9Y6X2

0

sumoylation

down-regulates

0.731

Stat3 mediated signaling pathways can be inhibited by pias3 (protein inhibitor of activated stat3), which was recently found to regulate protein stability and function by its sumo (small-ubiquitin like modifiers) ligase activity in promoting sumoylation of important nuclear proteins.

SIGNOR-124723

P27361

Q16204

1

phosphorylation

up-regulates activity

0.367

We have characterized the H4(D10S170) gene product, showing that it is a ubiquitously expressed 55 KDa nuclear and cytosolic protein that is phosphorylated following serum stimulation. This phosphorylation was found to depend on mitogen-activated protein kinase (MAPK) Erk1/2 activity and to be associated to the relocation of H4(D10S170) from the nucleus to the cytosol. S244 is the major target residue of ERK1

SIGNOR-276003

P98177

P48729

0

phosphorylation

down-regulates

0.2

Additionally, ck1, dyrk1a, and cdk2 also phosphorylate foxos at various sites to inhibit foxos activity.

SIGNOR-183664

Q13489

P57078

1

polyubiquitination

up-regulates activity

0.355

CIAP1/2 are direct E3 ligases conjugating diverse types of ubiquitin chains to receptor interacting proteins kinases 1 to 4 (RIP1-4).Together, our results demonstrate that depleting cIAP1/2 inhibits RIP1-4 mediated NF-kB activation without affecting RIP auto-phosphorylation.Lysine residues K51 and K145 of RIP4 are critical for cIAP1-mediated ubiquitination and NF-kB activation.

SIGNOR-272709

P52757

P06239

0

phosphorylation

down-regulates activity

0.2

We now demonstrate Lck-dependent phosphorylation of beta2-chimaerin in response to TCR triggering. We identify Tyr-153 as the Lck-dependent phosphorylation residue and show that its phosphorylation negatively regulates membrane stabilization of beta2-chimaerin, decreasing its GAP activity to Rac.

SIGNOR-276240

O43293

P24844

1

phosphorylation

up-regulates

0.487

More than a dozen kinases have been reported to phosphorylate the rlcs of nm ii (fig. 2), including myosin light chain kinase (mlck;also known as mylk), rho-associated, coiled coil-containing kinase (rock), citron kinase, leucine zipper interacting kinase (zipk;also known as dapk3) and myotonic dystrophy kinase-related cdc42-binding kinase (mrck;also known as cdc42bp)6,34,45,46. These kinases phosphorylate rlcs on ser19, thr18 or both, to relieve the inhibition imposed on the myosin molecule by unphosphorylated rlcs and the head_head interaction outlined above.

SIGNOR-188789

P09629

P09038

1

transcriptional regulation

up-regulates quantity by expression

0.396

Band shift and cotransfection experiments showed that HOXB7 directly transactivates the hFGF gene through one out of five putative homeodomain binding sites present in its promoter.

SIGNOR-261639

O75398

P60763

1

transcriptional regulation

up-regulates quantity by expression

0.2

Affymetrix gene profiling studies revealed Rac3 as a potential target gene and quantitative RT-PCR analysis confirmed that Rac3 was upregulated by Deaf-1 in immortalized mouse mammary epithelial cells.

SIGNOR-269059

P46934

P60321

1

ubiquitination

down-regulates quantity by destabilization

0.2

We find that NEDD4 targets an RNA-binding protein, NANOS2, in spermatogonia to destabilize it, leading to cell differentiation.|To examine whether complex formation of NEDD4 and NDFIP2 promotes NANOS2 ubiquitination in vivo, FLAG tagged NANOS2 was expressed in HEK293 cells with or without MYC-NEDD4 and MYC-NDFIP2.

SIGNOR-278770

Q2TAL8

Q9BW92

1

transcriptional regulation

up-regulates quantity by expression

0.2

QRICH1 promotes the expression of translation-related genes. our combined ChIP-seq and RNA-seq analyses identified that QRICH1 and ATF4 were enriched at the promoters of these specific tRNA synthetases, and that ER stress positively regulated their transcription (Fig. 4I). Together, these findings suggest that QRICH1 and ATF4 modulate tRNA metabolic processes to promote secreted protein synthesis during ER stress.

SIGNOR-269407

Q99717

P36894

0

phosphorylation

up-regulates activity

0.688

Two types of bmp-induced signaling pathways are known, the smad and p38 mapk pathways. In the former case, bmpr1 phosphorylates smad-1,-5,-8, which forms a complex with smad4 that translocates into the nucleus and regulates gene expression.

SIGNOR-255261

P49841

P49715

1

phosphorylation

up-regulates activity

0.379

Glycogen synthase kinase 3 (GSK3) phosphorylates T222 and T226, causing a conformational change in C/EBPα. GSK3-mediated phosphorylation does not, in itself, dramatically alter the activity of C/EBPα in our assays. phosphorylation of C/EBPalpha and other substrates by GSK3 may be required for adipogenesis, since treatment of differentiating preadipocytes with lithium inhibits their conversion to adipocytes.

SIGNOR-251231