GleghornLab/Signor_2class · Datasets at Hugging Face

IdA string	IdB string	labels int64	mechanism string	effect string	score float64	sentence string	signor_id string
Q96RK0	Q15418	0	phosphorylation	down-regulates	0.2	Specifically, 14-3-3 binds to p90(rsk)-phosphorylated ser?_??_ Of capic?_A thereby modulating dna binding to its hmg (high-mobility group) box, whereas erk phosphorylations prevent binding of a c-terminal nls (nuclear localization sequence) to importin ?4 (kpna3)	SIGNOR-169883
O43462	Q12772	1	cleavage	up-regulates activity	0.673	In order to activate transcription, the NH2-terminal domain of the SREBP must be released from the membrane so that it can enter the nucleus. This release has been studied most extensively for one of the SREBPs, namely, SREBP-2. However, the mechanism appears to be similar for the other SREBPs (SREBP-1a and -1c) (1). Release of the NH2-terminal domain is accomplished by a two-step proteolytic event that is regulated by sterols (3). In sterol-depleted mammalian cells, this proteolysis is initiated by the Site-1 protease (S1P), which cleaves human SREBP-2 between the Leu522-Ser523 bond in the sequence RSVL S (4). This cleavage requires formation of a complex between SREBP and SCAP, a polytopic membrane protein of the ER, and it is prevented when this complex is disrupted	SIGNOR-267498
Q9Y4K3	P40763	1	ubiquitination	down-regulates activity	0.47	TRAF6 Interacts with STAT3 and Mediates the Ubiquitination of STAT3.\|TRAF6 Represses the Transcriptional Activity of STAT3.	SIGNOR-278618
Q5JR12	P45983	0	phosphorylation	down-regulates	0.344	Specific phosphorylation of pp2czeta at ser (92) by stress-activated jnk attenuates its phosphatase activity in cells.	SIGNOR-178930
P55957	Q14790	0	cleavage	up-regulates activity	0.879	Caspase-8 cleaves bid at aspartic acid residue 60 (asp60) cleavage of bid by casp8 releases its potent proapoptotic activity	SIGNOR-59655
Q9Y6E7	P00367	1	glycosylation	down-regulates activity	0.62	We show that SIRT4 is a mitochondrial enzyme that uses NAD to ADP-ribosylate and downregulate glutamate dehydrogenase (GDH) activity.	SIGNOR-267828
O95239	Q96GD4	0	phosphorylation	up-regulates activity	0.517	Using in vitro kinase assays, we found that active AMPK and Aurora B phosphorylated KIF4A at Ser801 and Thr799 respectively in a time-dependent manner (Figure 5D). KIF4A is phosphoregulated by AMPK and Aurora B. Although AMPK phosphorylation increased the ATPase activity of KIF4A, Aurora B phosphorylation resulted in a stronger increase (Figure 5I), which might be consistent with the more powerful kinase function of Aurora B during mitosis.	SIGNOR-265992
P15172	P17252	0	phosphorylation	down-regulates activity	0.363	FGF inactivates myogenic helix-loop-helix proteins through phosphorylation of a conserved protein kinase C site in their DNA-binding domains.	SIGNOR-248845
Q04760	Q9UQM7	0	phosphorylation	up-regulates activity	0.2	This study is able to show that a phosphorylation of threonine-107 (T107) in the (rate-limiting) Glyoxalase 1 (Glo1) protein, mediated by Ca2+/calmodulin-dependent kinase II delta (CamKIIδ), is associated with elevated catalytic efficiency of Glo1 (lower KM; higher Vmax).	SIGNOR-273553
P12931	P51809	1	phosphorylation	up-regulates activity	0.286	We found that TI-VAMP is phosphorylated in vitro by c-Src kinase on tyrosine 45 of the Longin domain.Mimicking tyrosine 45 phosphorylation activates both t-SNARE binding and exocytosis of TI-VAMP.	SIGNOR-273819
P03372	Q15418	0	phosphorylation	up-regulates	0.494	Serine 167 is the major phosphorylation site on the human estrogen receptor. Phosphorylation is mediated by casein kinase ii.	SIGNOR-34113
Q13535	P33991	1	phosphorylation	up-regulates	0.724	Together these data strongly support the conclusion that mec1 directly targets the s/tq sites in mcm4 and mcm6, although it is formally possible that mec1 and mrc1 activate a different s/tq-directed kinase to target mcm4 and mcm6.	SIGNOR-169412
Q13351	Q92793	0	acetylation	up-regulates activity	0.49	EKLF residues acetylated by CREB binding protein (CBP) in vitro map to Lys-288 in its transactivation domain and Lys-302 in its zinc finger domain.	SIGNOR-251826
Q15154	O15182	1	relocalization	up-regulates	0.297	Rna silencing of pcm-1 leads to reduced assembly of centrin, pericentrin, and ninein at the centrosome	SIGNOR-95016
P49841	Q13148	0	post transcriptional regulation	down-regulates quantity by repression	0.267	Importantly, we found that TDP-43 protein could interact with GSK3β mRNA and regulate the level of GSK3β protein translation. Taken together, our findings suggest that TDP-43 may activate the Wnt/β-catenin pathway by targeting the inhibition of GSK3β protein translation\|TDP-43 activates Wnt/β-catenin pathway probably by inhibiting the GSK3β protein translation. A. Interaction between TDP-43 protein and GSK3β mRNA was analyzed using RIP assay.	SIGNOR-262113
Q9UQD0	P49841	0	phosphorylation	up-regulates activity	0.2	In vivo genetic manipulations demonstrate that GSK3β and Nav1.6 are molecular determinants of MSN excitability and that silencing of GSK3β prevents maladaptive plasticity of IC MSNs. In vitro studies reveal direct interaction of GSK3β with Nav1.6 and phosphorylation at Nav1.6T1936 by GSK3β. A GSK3β-Nav1.6T1936 competing peptide reduces MSNs excitability in IC, but not EC rats. These results identify GSK3β regulation of Nav1.6 as a biosignature of MSNs maladaptive plasticity.	SIGNOR-275763
P49427	Q9UBF6	0	polyubiquitination	down-regulates activity	0.748	SAG was found to be the second family member of Rbx (RING box protein) or ROC (Regulator of cullins) or Hrt that is a component of SCF E3 ubiquitin ligase. Indeed, like ROC1/Rbx1/Hrt1, SAG binds to Cul1 and SAG-Cul1 complex has ubiquitin ligase activity to promote poly-ubiquitination of E2/Cdc34.	SIGNOR-271443
Q05209	P24941	0	phosphorylation	down-regulates activity	0.382	In the present study, we found that S19 site phosphorylation of PTPN12 by CDK2 discharged its antitumor activity by down-regulation of its inhibitory role in cell migration, but not affecting its other regulatory functions.	SIGNOR-277366
Q15011	Q8IUR6	0	transcriptional regulation	up-regulates quantity by expression	0.2	Luman/CREB3 induces transcription of the endoplasmic reticulum (ER) stress response protein Herp through an ER stress response element.	SIGNOR-261575
Q00987	P25098	1	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
Q00535	P07101	1	phosphorylation	up-regulates activity	0.408	In addition, we demonstrate that co-expression of cdk5 and its regulatory activator p35 with TH increases the stability of TH.\|We show that cdk5 phosphorylates TH at serine 31 and that this phosphorylation is associated with an increase in total TH activity.	SIGNOR-279022
Q9NYL2	O14733	1	phosphorylation	up-regulates activity	0.2	We show here that members of the mixed-lineage kinase (MLK) family (including MLK1, MLK2, MLK3, and dual leucine zipper kinase [DLK]) are expressed in neuronal cells and are likely to act between Rac1/Cdc42 and MKK4 and -7 in death signaling.	SIGNOR-243345
P12931	O15492	1	phosphorylation	up-regulates	0.346	Src-mediated rgs16 tyrosine phosphorylation promotes rgs16 stability. / this result suggests src phosphorylates native rgs16 at residue tyr177 in vitro.	SIGNOR-98271
O60674	P40189	0	phosphorylation	up-regulates activity	0.639	All IL-6-type cytokines recruit gp130to their receptot complexes They either signal via gp130 alone [8] or in combination with LIFR [9] or the recently cloned OSMR [10], which are all able to activate Jaks proteins. Two tyrosine residues at the corresponding positions of Jak2 (tyrosine-1007 and tyrosine-1008) were found to be phosphorylated, and a single mutation of tyrosine-1007 eliminated essentially all tyrosine kinase activity [59].	SIGNOR-238634
P25098	P20941	1	phosphorylation	down-regulates activity	0.2	Phosphorylation of phosducin by GRK2 markedly reduces its G beta gamma binding ability\|The phosphorylation of purified phosducin and PhLP by recombinant GRK2 proceeds rapidly and stoichiometrically (0.82 +/- 0.1 and 0.83 +/- 0.09 mol of P(i)/mol of protein, respectively).	SIGNOR-279411
O43597	Q9BUB5	0	phosphorylation	down-regulates	0.531	The spry2/nedd4 association involves the ww domains of nedd4 and requires phosphorylation of the mnk2 kinase sites, ser(112) and ser(121), on spry2. mnk2 silencing decreased spry2-nedd4 interactions and also augmented the ability of spry2 to inhibit fibroblast growth factor signaling. endogenous and overexpressed nedd4 polyubiquitinate spry2 via lys(48) on ubiquitin and decrease its stability.	SIGNOR-188889
P35638	O75807	1	transcriptional regulation	up-regulates quantity by expression	0.454	ATF4 also induces another bZIP protein C/EBP-homologous protein (CHOP), which is responsible for triggering apoptosis in cells under prolonged ER stress. ATF4 and CHOP further induce growth arrest and DNA damage–inducible protein 34 (GADD34),a regulatory subunit of protein phosphatase 1 (PP1) that dephosphorylates eIF2α. This negative feedback mechanism enables protein synthesis to resume after resolution of ER stress.	SIGNOR-260173
Q13191	P04629	1	ubiquitination	down-regulates quantity	0.276	Cbl-b modulated TrkA ubiquitination and function in the dorsal root ganglion of mice.\|Viral expression of constitutively active Cbl-b in DRGs of osteoarthritic mice effectively repressed TrkA protein level and more importantly, alleviated mechanical allodynia and heat hyperalgesia.	SIGNOR-278690
Q8TEB7	P52565	1	polyubiquitination	up-regulates quantity by stabilization	0.266	We found that RhoGDIα and RhoGDIβ are ubiquitin E3 substrates of GRAIL. GRAIL uses nonlysine 48-ubiquitin linkage in polyubiquitinating RhoGDI. GRAIL was subsequently demonstrated to bind and ubiquitinate RhoGDI, although GRAIL-mediated ubiquitination of RhoGDI did not result in proteosomal degradation. Our data suggest that ubiquitination of RhoGDI by GRAIL does not result in proteolytic degradation. In fact, GRAIL activity appeared to increase RhoGDI stability.	SIGNOR-271622
O43521	O14965	0	phosphorylation	down-regulates quantity by destabilization	0.376	We observed that BimEL is phosphorylated by Aurora A early in mitosis and reversed by PP2A after mitotic exit. Aurora A phosphorylation stimulated binding of BimEL to the F-box protein beta-transducin repeat containing E3 ubiquitin protein ligase and promoted ubiquitination and degradation of BimEL.	SIGNOR-276248
Q13309	P11309	0	phosphorylation	up-regulates activity	0.34	We found that expression of Pim-1 increases the level of Skp2 through direct binding and phosphorylation of multiple sites on this protein. Along with known Skp2 phosphorylation sites including Ser(64) and Ser(72), we have identified Thr(417) as a unique Pim-1 phosphorylation target. Phosphorylation of Thr(417) controls the stability of Skp2 and its ability to degrade p27.	SIGNOR-259819
P61586	Q13618	0	ubiquitination	down-regulates quantity by destabilization	0.396	BACURDs form ubiquitin ligase complexes, which selectively ubiquitinate RhoA, with Cul3. Our studies reveal a previously unknown mechanism for controlling RhoA degradation and regulating RhoA function in various biological contexts, which involves a Cul3/BACURD ubiquitin ligase complex.	SIGNOR-264238
P41229	Q99814	0	transcriptional regulation	up-regulates quantity by expression	0.278	To this end, we confirm that KDM3A, KDM4B, KDM4C, KDM5B, KDM5C, and KDM62 are direct targets of HIF-1a while extent the list of known targets to KDM2A, KDM2B, KDM4D, KDM5A, and KDM6A. The results demonstrated that majority of the KDMs were similarly induced (KDM2A, KDM2B, KDM3A, KDM4B, KDM4C, KDM4D, KDM5A, KDM5B, KDM5C, KDM6B, and KDM7A) or repressed (KDM NO66 and KDM1A) by both HIF-1a and HIF-2a.	SIGNOR-271579
P48436	Q13464	0	phosphorylation	up-regulates	0.305	Rho kinase-dependent activation of sox9 in chondrocytes. In vitro, rock directly phosphorylated sox9 at ser(181), and the overexpression of rock or the activation of the rhoa pathway in sw1353 chondrosarcoma cells increased sox9(ser181) phosphorylation	SIGNOR-162643
Q9UBF6	Q8TB45	1	ubiquitination	down-regulates activity	0.299	SAG (Sensitive to Apoptosis Gene), also known as RBX2 (RING box protein 2), ROC2 (Regulator of Cullins 2), or RNF7 (RING Finger Protein 7), was originally cloned in our laboratory as a redox inducible antioxidant protein and later characterized as the second member of the RBX/ROC RING component of the SCF (SKP1-CUL-F-box Proteins) E3 ubiquitin ligase. by forming a complex with other components of the SCF E3 ligase, SAG promotes ubiquitination and degradation of a number of protein substrates, including c-JUN, DEPTOR, HIF-1α, IκBα, NF1, NOXA, p27, and procaspase-3, thus regulating various signaling pathways and biological processes.	SIGNOR-271449
P41180	P05771	0	phosphorylation	down-regulates activity	0.319	Expression of a mutant CaR in which the major PKC phosphorylation site is altered by substitution of alanine for threonine (T888A) eliminated oscillatory behavior, producing [Ca(2+)](i) responses almost identical to those produced by the wild type CaR exposed to PKC inhibitors. These results support a model in which phosphorylation of the CaR at the inhibitory threonine 888 by PKC provides the negative feedback needed to cause [Ca(2+)](i) oscillations mediated by this receptor.	SIGNOR-249176
Q14653	Q13043	0	phosphorylation	up-regulates activity	0.2	Beyond that, another investigation demonstrated that MST1 directly phosphorylated IRF3 at T75 and T253, which disrupted the dimerization of IRF3 and restrained RLRs and cGAS-mediated innate antiviral response.	SIGNOR-280145
Q13315	A1Z1Q3	1	phosphorylation	down-regulates activity	0.2	We found that MacroD2 is exported from the nucleus upon DNA damage and that this depends on the ATM-induced phosphorylation of the MacroD2 C-terminal IDR.\|ATM activation leads to phosphorylation of the MacroD2 C-terminal region.	SIGNOR-279792
Q13426	P78527	0	phosphorylation	up-regulates activity	0.907	In response to ionizing radiation, ATM phosphorylates FBXW7 at serine 26 to recruit it to DNA double-strand break (DSB) sites, whereas activated DNA-PKcs phosphorylates XRCC4 at serines 325/326, which promotes binding of XRCC4 to FBXW7. SCF(FBXW7) E3 ligase then promotes polyubiquitylation of XRCC4 at lysine 296 via lysine 63 linkage for enhanced association with the Ku70/80 complex to facilitate NHEJ repair.	SIGNOR-277198
P08069	O00443	1	phosphorylation	up-regulates	0.275	Analysis of the ability of the full-length igfr and its mutant receptors described above to associate with phosphatidylinositol 3 kinase indicated that the association required ptk activity and tyrosine [?] Phosphorylation of the receptors and correlated well with their transforming activities	SIGNOR-32076
O00165	Q8TCJ0	0	ubiquitination	down-regulates quantity by destabilization	0.331	FBXO25 encodes an orphan F-box protein that determines the substrate specificity of the SCF (SKP1-CUL1-F-box)(FBXO25) ubiquitin ligase complex. An unbiased screen uncovered the prosurvival protein HCLS1-associated protein X-1 (HAX-1) as the bona fide substrate of FBXO25 that is targeted after apoptotic stresses. Protein kinase Cdelta (PRKCD) initiates this process by phosphorylating FBXO25 and HAX-1, thereby spatially directing nuclear FBXO25 to mitochondrial HAX-1.	SIGNOR-275563
P46934	O75896	1	ubiquitination	down-regulates quantity by destabilization	0.2	NEDD4 Degrades TUSC2 to Promote Glioblastoma Progression.\|NEDD4 E3 ubiquitin ligase polyubiquitinates TUSC2 at residue K71, and the TUSC2-K71R mutant is resistant to NEDD4-mediated proteasomal degradation.	SIGNOR-278638
Q6J9G0	Q14457	1	phosphorylation	up-regulates activity	0.2	We also demonstrated that STYK1 elevated the serine phosphorylation of BECN1, thereby decreasing the interaction between BECN1 and BCL2. \|The results indicated that the level of BECN1 S90 phosphorylation significantly increased after STYK1 overexpression, but not STYK1K147R mutant.\|STYK1 promotes autophagy through enhancing the assembly of autophagy-specific class III phosphatidylinositol 3-kinase complex I	SIGNOR-264568
Q13115	P28482	1	dephosphorylation	down-regulates activity	0.762	Dephosphorylation and Inactivation of ERKs\|A single protein kinase, MEK, activates ERK2 by phosphorylating threonine 183 and tyrosine 185	SIGNOR-248718
Q05655	P68431	1	phosphorylation	up-regulates activity	0.2	We identify protein kinase c-delta as the kinase responsible for h3t45ph in vitro and in vivo. Given the nucleosomal position of h3t45, we postulate that h3t45ph induces structural change within the nucleosome to facilitate dna nicking and/or fragmentation.	SIGNOR-185144
Q7Z2W7	P17612	0	phosphorylation	up-regulates activity	0.2	Using specific pharmacological and molecular tools combined with patch-clamp current recordings, we found that in heterologously expressed HEK-293 (human embryonic kidney) cells, TRPM8 channel is inhibited by the G(i) protein/adenylate cyclase (AC)/cAMP/protein kinase A (PKA) signaling cascade. We further identified the TRPM8 S9 and T17 as two key PKA phosphorylation sites regulating TRPM8 channel activity. the intracellular serine/threonine protein phosphatase 2A (PP2A) dephosphorylates TRPM8 Ser-9 and Thr-17 inhibiting the channel activity.	SIGNOR-273791
P60953	Q92502	0	gtpase-activating protein	down-regulates activity	0.511	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-260520
P21127	Q9UQ88	0	phosphorylation	up-regulates	0.305	Overall, our data indicated that thr-370 is responsible for the autophosphorylation, dimerization, and kinase activity of cdk11(p58)	SIGNOR-169628
P04626	P49327	1	phosphorylation	up-regulates activity	0.442	Conversely, HER2 directly phosphorylates and activates FASN, while it also promotes FASN gene expression ( xref ; xref ).\|Conversely, HER2 directly phosphorylates and activates FASN, while it also promotes FASN gene expression.	SIGNOR-278399
P17655	P55085	1	cleavage	down-regulates activity	0.298	PAR1E and PAR2E (10 microM) were incubated in the presence of the different proteases \| The enzymes were used at the following concentrations: 0.5 unit/mL thrombin, 2.5 nM trypsin, 20 nM plasmin, 20 nM cathepsin G, 20 nM elastase, 20 nM proteinase 3, and 2 units/mL calpain I and II\|Protease-activated receptors (PARs) mediate cell activation after proteolytic cleavage of their extracellular amino terminus.\|Mass spectrometry studies of PAR2E predicted activation of PAR2 by trypsin through cleavage at the Arg36-Ser37 site, no effect of thrombin, and inactivation of the receptor by plasmin, calpain and leukocyte elastase, cathepsin G, and proteinase 3	SIGNOR-263581
Q9H4B4	O96017	1	phosphorylation	up-regulates activity	0.66	Plk3 phosphorylates Chk2 at two residues, serine 62 (S62) and serine 73 (S73) in vitro, and this phosphorylation facilitates subsequent phosphorylation of Chk2 on T68 by ATM in response to DNA damage. When the Chk2 mutant construct GFP-Chk2 S73A (serine 73 mutated to alanine) is transfected into cells, it no longer associates with a large complex in vivo, and manifests a significant reduction in kinase activity.	SIGNOR-276051
Q14493	Q7L7L0	1	translation regulation	up-regulates quantity by expression	0.2	Synthesis of mature histone mRNA requires only a single processing reaction: an endonucleolytic cleavage between a conserved stem-loop and a purine-rich downstream element to form the 3' end. The stem-loop binding protein (SLBP) is required for processing, and following processing, histone mRNA is transported to the cytoplasm, where SLBP participates in translation of the histone mRNA\|We used radiolabeled probes generated by PCR targeting the open reading frame (ORF) to detect histones H2A, H2B, H3, H4, and H1 and used 7SK snRNA as a loading control (Fig. 2A). The abundance of histone H2A, H2B, H3, and H4 mRNAs is reduced to 37% to 70% of control levels in the SLBP knockdown cells when compared to the C2 control.	SIGNOR-265409
P01584	Q04206	0	transcriptional regulation	down-regulates activity	0.555	Early Inhibition of IL-1 beta Expression by IFN-gamma Is Mediated by Impaired Binding of NF-kappa B to the IL-1 beta Promoter but Is Independent of Nitric Oxide\|We report that IFN-γ suppressed bacterial RNA and LPS induced IL-1β transcription in primary murine macrophages	SIGNOR-251736
P51843	Q96EP0	0	monoubiquitination	up-regulates quantity by stabilization	0.437	RNF31 promotes monoubiquitination of DAX-1 in an RBR domain-dependent manner. In conclusion, our results suggest that the major DAX-1 modification observed in different experimental settings is likely to be monoubiquitination at one or more lysine residues (multiubiquitination) possibly located within the LBD of DAX-1. RNF31 stabilizes endogenous DAX-1.	SIGNOR-271786
P56945	P00519	0	phosphorylation	up-regulates activity	0.462	Abl silencing inhibits CAS mediated process and constriction in resistance arteries.\|CAS phosphorylation was catalyzed by Abl in an in vitro study.	SIGNOR-279671
P48764	O00141	0	phosphorylation	up-regulates activity	0.433	The NHE3 activation by SGK1 is dependent on their combined interaction with NHERF2 and then phosphorylation at S663 of NHE3 by SGK1 ( xref , xref ).	SIGNOR-279112
Q16513	O15530	0	phosphorylation	up-regulates	0.705	It is shown that activation in vitro and in vivo involves the activation loop phosphorylation of prk1/2 by 3-phosphoinositide-dependent protein kinase-1 (pdk1) /pdk1 phosphorylates the prks at their conserved activation loop threonines (thr-774 and thr-816 for prk1 and prk2, respectively)	SIGNOR-76710
Q8IZQ8	P17252	0	phosphorylation	down-regulates activity	0.2	PKCalpha directly promoted the basal phosphorylation of endogenous myocardin at serine and threonine residues.	SIGNOR-279099
Q15831	Q13131	1	phosphorylation	up-regulates activity	0.599	The AMP-activated protein kinase (AMPK) is a critical regulator of energy balance at both the cellular and whole-body levels. Two upstream kinases have been reported to activate AMPK in cell-free assays, i.e., the tumor suppressor LKB1 and calmodulin-dependent protein kinase kinase.	SIGNOR-139297
Q99607	Q13315	0	phosphorylation	down-regulates activity	0.349	Elf4 is phosphorylated by Atm after gamma irradiation, leading to its degradation.\|Thus, Atm promotes Elf4 protein degradation after gamma irradiation via phosphorylation at these sites.	SIGNOR-278466
Q9NQU5	Q16539	0	phosphorylation	up-regulates	0.2	The activation of pak6 by both p38 map kinase and mkk6 suggests that pak6 plays a role in the cellular response to stress-related signals.	SIGNOR-130979
P42575	P68400	0	phosphorylation	down-regulates	0.309	Here we show that protein kinase (pk) ck2 phosphorylates procaspase-2 directly at serine-157. When intracellular pkck2 activity is low or downregulated by specific inhibitors, procaspase-2 is dephosphorylated, dimerized, and activated in a piddosome-independent manner.	SIGNOR-140836
A8MYZ6	Q12857	0	transcriptional regulation	down-regulates quantity	0.2	By integrating transcriptomic profiling (RNA-seq) of Nfia- and Nfix-deficient GNPs with epigenomic profiling (ChIP-seq against NFIA, NFIB and NFIX, and DNase I hypersensitivity assays), we reveal that these transcription factors share a large set of potential transcriptional targets, suggestive of complementary roles for these NFI family members in promoting neural development	SIGNOR-268875
P28482	Q9HBH9	1	phosphorylation	up-regulates	0.6	We have identified a new subfamily of murine serine/threonine kinases, whose members, map kinase-interacting kinase 1 (mnk1) and mnk2, bind tightly to the growth factor-regulated map kinases, erk1 and erk2erk and p38 phosphorylate mnk1 and mnk2, which stimulates their in vitro kinase activity	SIGNOR-48338
P35568	P23458	0	phosphorylation	up-regulates activity	0.708	Janus kinase-dependent activation of insulin receptor substrate 1	SIGNOR-251343
P41221	Q14938	0	transcriptional regulation	down-regulates quantity	0.2	By integrating transcriptomic profiling (RNA-seq) of Nfia- and Nfix-deficient GNPs with epigenomic profiling (ChIP-seq against NFIA, NFIB and NFIX, and DNase I hypersensitivity assays), we reveal that these transcription factors share a large set of potential transcriptional targets, suggestive of complementary roles for these NFI family members in promoting neural development	SIGNOR-268889
P35790	Q9ULK5	1	phosphorylation	down-regulates activity	0.2	CKI\u03b5-dependent phosphorylation increases Stbm turnover at junctions, and thus promotes complex sorting, while phosphorylation of Dsh decreases its turnover.\|Interestingly, CKI\u03b5 has been implicated in phosphorylation of both Stbm and Dsh.	SIGNOR-278925
P53350	O14641	1	phosphorylation	up-regulates	0.465	Dvl2 bound to and was phosphorylated at thr206 by a mitotic kinase, polo-like kinase 1 (plk1), and this phosphorylation was required for spindle orientation and stable microtubule (mt)-kt attachment	SIGNOR-167858
Q9H2B2	P45983	0	phosphorylation	up-regulates activity	0.411	JNK phosphorylates Syt 4 at Ser135 in vitro and in vivo.	SIGNOR-273673
Q15858	P10275	0	transcriptional regulation	up-regulates quantity by expression	0.2	In neuroblastoma ND7 cells, a nuclear interaction between the developmentally regulated transcription factor Brn-3a and AR resulted in a complex which bound to multiple elements within the promoter region of SCN9A (Nav1.7) and upregulated channel expression.	SIGNOR-253466
P17612	Q9UL62	1	phosphorylation	down-regulates quantity	0.2	Together, these results suggest that TRPC5 is directly phosphorylated by G(s)/cAMP/PKA at positions S794 and S796. These inhibitory effects were blocked by the protein kinase A (PKA) inhibitors, KT-5720 and H-89, as well as by two point mutations at consensus PKA phosphorylation sites on TRPC5 (S794A and S796A).	SIGNOR-277823
P12830	O60729	0	dephosphorylation	up-regulates activity	0.313	Cdc14B activates APC/C Cdh1 after DNA damage in G2.\|Importantly, after DNA damage, thein vivo phosphorylation of wild type Cdh1 - but not that of Cdh1 (4xA) - increased after Cdc14B silencing (XREF_FIG), indicating that in response to genotoxic stress, Cdc14B dephosphorylates Cdh1 on the four sites phosphorylated by Cdk2.	SIGNOR-277017
Q00535	P06241	0	phosphorylation	up-regulates activity	0.608	Constitutively active Fyn phosphorylated Tyr15 of Cdk5. Fyn Facilitates Kinase Activity of Cdk5 Via Tyr15 Phosphorylation	SIGNOR-251156
Q05655	P05230	1	phosphorylation	up-regulates quantity	0.2	Translocated FGF1 can be phosphorylated by PKC\u03b4 on serine 130.	SIGNOR-278451
P35900	P49137	0	phosphorylation	up-regulates activity	0.2	P38 phosphorylates the type II keratin, K8 at Ser73, whereas MK2 phosphorylates the binding partners K18 at Ser52 and K20 at Ser13.	SIGNOR-263071
P10912	Q13163	1	phosphorylation	up-regulates activity	0.2	The MEK5-dependent activation of ERK5 promotes binding of the transcription factor SP1 to the promoter of the genes encoding the transcription factors Klf2 and Klf4, leading to their increased abundance. Subsequently, Klf2 and Klf4 bind to the Npnt promoter and induce the production of nephronectin during myoblast fusion	SIGNOR-255452
P35638	P68400	0	phosphorylation	down-regulates activity	0.344	CHOP transcription factor phosphorylation by casein kinase 2 inhibits transcriptional activation. \| The serine to alanine substituted site CHOP mutant was not phosphorylated by CK2, indicating that serines 14–15 and 30–31 of CHOP are the CK2 phosphoacceptor sites	SIGNOR-250850
P36894	Q99717	1	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
Q04721	P49841	0	phosphorylation	down-regulates activity	0.481	We show that gsk-3beta directly binds at c-terminal of the notch2 ankyrin repeats and phosphorylates thr-2068 and/or ser-2070, thr-2074, and thr-2093.	SIGNOR-101570
P00519	Q92769	1	phosphorylation	up-regulates quantity by stabilization	0.285	C-Abl stabilizes HDAC2 levels by tyrosine phosphorylation repressing neuronal gene expression in Alzheimer's disease.	SIGNOR-260928
P06730	Q9BUB5	0	phosphorylation	up-regulates	0.779	Mnk1 and mnk2 regulate protein synthesis by phosphorylating the initiation factor eif4e.	SIGNOR-166646
P24941	O15350	1	phosphorylation	down-regulates activity	0.575	Cyclin-dependent kinases phosphorylate p73 at threonine 86 in a cell cycle-dependent manner and negatively regulate p73.Furthermore, cyclin a/cdk1/2, cyclin b/cdk1/2, and cyclin e/cdk2 complexes can phosphorylate multiple p73 isoforms in vitro at threonine 86.	SIGNOR-99746
O15162	P12931	0	phosphorylation	up-regulates activity	0.476	Plscr1 is phosphorylated by c-src, within the tandem repeat sequence 68vynqpvynqp77.\|The EGF-mediated Interaction between PLSCR1 and Shc Requires Phosphorylation of Tyr69 and Tyr74 in PLSCR1	SIGNOR-103773
Q6IAA8	Q05086	0	ubiquitination	down-regulates quantity by destabilization	0.2	Ube3a regulates mTORC1 signaling by targeting p18, a subunit of the Ragulator. Ube3a ubiquinates p18, resulting in its proteasomal degradation, and Ube3a deficiency in the hippocampus of AS mice induces increased lysosomal localization of p18 and other members of the Ragulator-Rag complex, and increased mTORC1 activity	SIGNOR-256145
O60346	P49841	0	phosphorylation	down-regulates	0.353	In addition, we show that the beta-trcp-mediated degradation requires phosphorylation of phlpp1 by casein kinase i and glycogen synthase kinase 3beta (gsk-3beta), and activation of the phosphatidylinositol 3-kinase/akt pathway suppresses the degradation of phlpp1 by inhibiting the gsk-3beta activity.	SIGNOR-188330
Q06187	P07948	0	phosphorylation	up-regulates	0.545	Phosphorylation at y551 requires lyn kinase activity, indicating that y551 is a transphosphorylation site \ this transphosphorylation at y551 is followed by phosphorylation at a second site, which is dependent on btk catalytic activity.	SIGNOR-41607
P27540	P04798	1	transcriptional regulation	up-regulates quantity by expression	0.646	Kaempferol proved to be capable of inhibiting binding of agonist and agonist-induced formation of the AHR/ARNT DNA-binding complex and upregulation of the AHR target gene, CYP1A1.	SIGNOR-259910
Q96I59	P18848	0	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-269423
P05023	P28482	0	phosphorylation	down-regulates activity	0.519	Parathyroid hormone (PTH) inhibits Na+,K+-ATPase activity through protein kinase C- (PKC) and extracellular signal-regulated kinase- (ERK) dependent pathways and increases serine phosphorylation of the α1-subunit. These results suggest that PTH regulates Na(+),K(+)-ATPase by PKC and ERK-dependent alpha(1)-subunit phosphorylation and that the phosphorylation requires the expression of a serine at the 11 position of the Na(+),K(+)-ATPase alpha(1)-subunit.	SIGNOR-262940
O14745	Q15418	0	phosphorylation	up-regulates activity	0.33	In summary, these results demonstrate that Ras-RSK1 signaling promotes nuclear localization of EBP50.\|Specifically, RSK1 phosphorylates EBP50 at threonine 156 (T156) residue in a cell cycle dependent manner, which is important for nuclear translocation of EBP50 to facilitate cellular proliferation and transformation.	SIGNOR-278290
Q96J02	Q9HBA0	1	ubiquitination	down-regulates activity	0.377	AIP4 ubiquitin ligase is involved in the ubiquitination of both TRPV4 and TRPC4.Ubiquitination of TRPV4 is dramatically increased by the HECT (homologous to E6-AP carboxyl terminus)-family ubiquitin ligase AIP4 without inducing degradation of this channel. Instead, AIP4 promotes the endocytosis of TRPV4 and decreases its amount at the plasma membrane.	SIGNOR-272625
O95684	Q15691	1	relocalization	up-regulates	0.2	Fop also binds to eb1 and is required for localizing eb1 to the centrosome	SIGNOR-142400
Q9UQD0	Q13557	0	phosphorylation	up-regulates activity	0.281	CaMKII enhances voltage-gated sodium channel Nav1.6 activity and neuronal excitability\|mmobilized peptide arrays and nanoflow LC-electrospray ionization/MS of Nav1.6 reveal potential sites of CaMKII phosphorylation, specifically Ser-561 and Ser-641/Thr-642 within the first intracellular loop of the channel.	SIGNOR-275792
P11474	Q9H0X6	1	transcriptional regulation	up-regulates quantity by expression	0.2	Furthermore, RNF208 was induced by 17β-estradiol (E2) treatment in an estrogen receptor alpha (ΕRα)-dependent manner	SIGNOR-269052
P43003	O00141	0	phosphorylation	up-regulates activity	0.415	Site‐directed mutagenesis of the SGK1 phosphorylation sites in the Nedd4‐2 protein (S382A,S468ANedd4‐2) and in the EAAT1 protein (T482AEAAT1, T482DEAAT1) significantly blunts the effect of S422DSGK1. Introduction of a negative charge at the SGK phosphorylation site in the EAAT1 protein leads to a strong stimulation of the carrier, whereas replacement with alanine markedly decreases the EAAT1‐mediated current. These observations suggest that SGK1 exerts its effect not only by phosphorylation of Nedd4‐2 but also by phosphorylation of EAAT1.	SIGNOR-263075
Q13315	Q96P70	1	phosphorylation	up-regulates activity	0.2	In line with our previous results, IR exposure induced the nuclear accumulation of RanBP9, which was prevented by ATM inhibition using KU-55933.\|Taken together these data indicate that RanBP9 is a novel target of ATM and that ATM phosphorylates at least two different residues (S181 and S603) of RanBP9 following IR exposure.	SIGNOR-278910
Q7Z434	Q14258	0	polyubiquitination	down-regulates quantity by destabilization	0.77	We report here that RLR activation triggers MAVS ubiquitination on lysine 7 and 10 by the E3 ubiquitin ligase TRIM25 and marks it for proteasomal degradation concomitantly with downstream signaling.	SIGNOR-272042
Q13315	Q15109	1	phosphorylation	up-regulates activity	0.2	RAGE is phosphorylated at Serine 376 and Serine 389 by the ATM kinase and is recruited to the site of DNA-DSBs via an early DNA damage response.	SIGNOR-278907
P18754	P06493	0	phosphorylation	up-regulates activity	0.504	We show here that Cdc2 kinase phosphorylates the serines located in or near the nuclear localization signal (NLS) of hum an RCC1, the nucleotide exchange factor for Ran. This phosphorylation is necessary for RCC1 to generate RanGTP on mitotic chromosomes in mammalian cells, which in turn is required for spindle assembly and chromosome segregation. However, when both S2 and S11 were simultaneously mutated to As, the resulting 6His-RCC1S2,11A failed to be phosphorylated, whereas all of the other double mutants were phosphorylated (Fig. 1C). As expected, mutating all four sites to As (the 6His-RCC1S2,11,387A-T274A) also blocked phosphorylation (Fig. 1C).	SIGNOR-262704
O76050	O76083	1	polyubiquitination	down-regulates quantity by destabilization	0.2	Neuralized family member NEURL1 is a ubiquitin ligase for the cGMP-specific phosphodiesterase 9A. We also demonstrate that NEURL1 can promote polyubiquitination of PDE9A that leads to its proteasome-mediated degradation mainly via lysine residue K27 of ubiquitin.	SIGNOR-272305

Q96RK0

Q15418

0

phosphorylation

down-regulates

0.2

Specifically, 14-3-3 binds to p90(rsk)-phosphorylated ser?_??_ Of capic?_A thereby modulating dna binding to its hmg (high-mobility group) box, whereas erk phosphorylations prevent binding of a c-terminal nls (nuclear localization sequence) to importin ?4 (kpna3)

SIGNOR-169883

O43462

Q12772

1

cleavage

up-regulates activity

0.673

In order to activate transcription, the NH2-terminal domain of the SREBP must be released from the membrane so that it can enter the nucleus. This release has been studied most extensively for one of the SREBPs, namely, SREBP-2. However, the mechanism appears to be similar for the other SREBPs (SREBP-1a and -1c) (1). Release of the NH2-terminal domain is accomplished by a two-step proteolytic event that is regulated by sterols (3). In sterol-depleted mammalian cells, this proteolysis is initiated by the Site-1 protease (S1P), which cleaves human SREBP-2 between the Leu522-Ser523 bond in the sequence RSVL S (4). This cleavage requires formation of a complex between SREBP and SCAP, a polytopic membrane protein of the ER, and it is prevented when this complex is disrupted

SIGNOR-267498

Q9Y4K3

P40763

1

ubiquitination

down-regulates activity

0.47

TRAF6 Interacts with STAT3 and Mediates the Ubiquitination of STAT3.|TRAF6 Represses the Transcriptional Activity of STAT3.

SIGNOR-278618

Q5JR12

P45983

0

phosphorylation

down-regulates

0.344

Specific phosphorylation of pp2czeta at ser (92) by stress-activated jnk attenuates its phosphatase activity in cells.

SIGNOR-178930

P55957

Q14790

0

cleavage

up-regulates activity

0.879

Caspase-8 cleaves bid at aspartic acid residue 60 (asp60) cleavage of bid by casp8 releases its potent proapoptotic activity

SIGNOR-59655

Q9Y6E7

P00367

1

glycosylation

down-regulates activity

0.62

We show that SIRT4 is a mitochondrial enzyme that uses NAD to ADP-ribosylate and downregulate glutamate dehydrogenase (GDH) activity.

SIGNOR-267828

O95239

Q96GD4

0

phosphorylation

up-regulates activity

0.517

Using in vitro kinase assays, we found that active AMPK and Aurora B phosphorylated KIF4A at Ser801 and Thr799 respectively in a time-dependent manner (Figure 5D). KIF4A is phosphoregulated by AMPK and Aurora B. Although AMPK phosphorylation increased the ATPase activity of KIF4A, Aurora B phosphorylation resulted in a stronger increase (Figure 5I), which might be consistent with the more powerful kinase function of Aurora B during mitosis.

SIGNOR-265992

P15172

P17252

0

phosphorylation

down-regulates activity

0.363

FGF inactivates myogenic helix-loop-helix proteins through phosphorylation of a conserved protein kinase C site in their DNA-binding domains.

SIGNOR-248845

Q04760

Q9UQM7

0

phosphorylation

up-regulates activity

0.2

This study is able to show that a phosphorylation of threonine-107 (T107) in the (rate-limiting) Glyoxalase 1 (Glo1) protein, mediated by Ca2+/calmodulin-dependent kinase II delta (CamKIIδ), is associated with elevated catalytic efficiency of Glo1 (lower KM; higher Vmax).

SIGNOR-273553

P12931

P51809

1

phosphorylation

up-regulates activity

0.286

We found that TI-VAMP is phosphorylated in vitro by c-Src kinase on tyrosine 45 of the Longin domain.Mimicking tyrosine 45 phosphorylation activates both t-SNARE binding and exocytosis of TI-VAMP.

SIGNOR-273819

P03372

Q15418

0

phosphorylation

up-regulates

0.494

Serine 167 is the major phosphorylation site on the human estrogen receptor. Phosphorylation is mediated by casein kinase ii.

SIGNOR-34113

Q13535

P33991

1

phosphorylation

up-regulates

0.724

Together these data strongly support the conclusion that mec1 directly targets the s/tq sites in mcm4 and mcm6, although it is formally possible that mec1 and mrc1 activate a different s/tq-directed kinase to target mcm4 and mcm6.

SIGNOR-169412

Q13351

Q92793

0

acetylation

up-regulates activity

0.49

EKLF residues acetylated by CREB binding protein (CBP) in vitro map to Lys-288 in its transactivation domain and Lys-302 in its zinc finger domain.

SIGNOR-251826

Q15154

O15182

1

relocalization

up-regulates

0.297

Rna silencing of pcm-1 leads to reduced assembly of centrin, pericentrin, and ninein at the centrosome

SIGNOR-95016

P49841

Q13148

0

post transcriptional regulation

down-regulates quantity by repression

0.267

Importantly, we found that TDP-43 protein could interact with GSK3β mRNA and regulate the level of GSK3β protein translation. Taken together, our findings suggest that TDP-43 may activate the Wnt/β-catenin pathway by targeting the inhibition of GSK3β protein translation|TDP-43 activates Wnt/β-catenin pathway probably by inhibiting the GSK3β protein translation. A. Interaction between TDP-43 protein and GSK3β mRNA was analyzed using RIP assay.

SIGNOR-262113

Q9UQD0

P49841

0

phosphorylation

up-regulates activity

0.2

In vivo genetic manipulations demonstrate that GSK3β and Nav1.6 are molecular determinants of MSN excitability and that silencing of GSK3β prevents maladaptive plasticity of IC MSNs. In vitro studies reveal direct interaction of GSK3β with Nav1.6 and phosphorylation at Nav1.6T1936 by GSK3β. A GSK3β-Nav1.6T1936 competing peptide reduces MSNs excitability in IC, but not EC rats. These results identify GSK3β regulation of Nav1.6 as a biosignature of MSNs maladaptive plasticity.

SIGNOR-275763

P49427

Q9UBF6

0

polyubiquitination

down-regulates activity

0.748

SAG was found to be the second family member of Rbx (RING box protein) or ROC (Regulator of cullins) or Hrt that is a component of SCF E3 ubiquitin ligase. Indeed, like ROC1/Rbx1/Hrt1, SAG binds to Cul1 and SAG-Cul1 complex has ubiquitin ligase activity to promote poly-ubiquitination of E2/Cdc34.

SIGNOR-271443

Q05209

P24941

0

phosphorylation

down-regulates activity

0.382

In the present study, we found that S19 site phosphorylation of PTPN12 by CDK2 discharged its antitumor activity by down-regulation of its inhibitory role in cell migration, but not affecting its other regulatory functions.

SIGNOR-277366

Q15011

Q8IUR6

0

transcriptional regulation

up-regulates quantity by expression

0.2

Luman/CREB3 induces transcription of the endoplasmic reticulum (ER) stress response protein Herp through an ER stress response element.

SIGNOR-261575

Q00987

P25098

1

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

Q00535

P07101

1

phosphorylation

up-regulates activity

0.408

In addition, we demonstrate that co-expression of cdk5 and its regulatory activator p35 with TH increases the stability of TH.|We show that cdk5 phosphorylates TH at serine 31 and that this phosphorylation is associated with an increase in total TH activity.

SIGNOR-279022

Q9NYL2

O14733

1

phosphorylation

up-regulates activity

0.2

We show here that members of the mixed-lineage kinase (MLK) family (including MLK1, MLK2, MLK3, and dual leucine zipper kinase [DLK]) are expressed in neuronal cells and are likely to act between Rac1/Cdc42 and MKK4 and -7 in death signaling.

SIGNOR-243345

P12931

O15492

1

phosphorylation

up-regulates

0.346

Src-mediated rgs16 tyrosine phosphorylation promotes rgs16 stability. / this result suggests src phosphorylates native rgs16 at residue tyr177 in vitro.

SIGNOR-98271

O60674

P40189

0

phosphorylation

up-regulates activity

0.639

All IL-6-type cytokines recruit gp130to their receptot complexes They either signal via gp130 alone [8] or in combination with LIFR [9] or the recently cloned OSMR [10], which are all able to activate Jaks proteins. Two tyrosine residues at the corresponding positions of Jak2 (tyrosine-1007 and tyrosine-1008) were found to be phosphorylated, and a single mutation of tyrosine-1007 eliminated essentially all tyrosine kinase activity [59].

SIGNOR-238634

P25098

P20941

1

phosphorylation

down-regulates activity

0.2

Phosphorylation of phosducin by GRK2 markedly reduces its G beta gamma binding ability|The phosphorylation of purified phosducin and PhLP by recombinant GRK2 proceeds rapidly and stoichiometrically (0.82 +/- 0.1 and 0.83 +/- 0.09 mol of P(i)/mol of protein, respectively).

SIGNOR-279411

O43597

Q9BUB5

0

phosphorylation

down-regulates

0.531

The spry2/nedd4 association involves the ww domains of nedd4 and requires phosphorylation of the mnk2 kinase sites, ser(112) and ser(121), on spry2. mnk2 silencing decreased spry2-nedd4 interactions and also augmented the ability of spry2 to inhibit fibroblast growth factor signaling. endogenous and overexpressed nedd4 polyubiquitinate spry2 via lys(48) on ubiquitin and decrease its stability.

SIGNOR-188889

P35638

O75807

1

transcriptional regulation

up-regulates quantity by expression

0.454

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

SIGNOR-260173

Q13191

P04629

1

ubiquitination

down-regulates quantity

0.276

Cbl-b modulated TrkA ubiquitination and function in the dorsal root ganglion of mice.|Viral expression of constitutively active Cbl-b in DRGs of osteoarthritic mice effectively repressed TrkA protein level and more importantly, alleviated mechanical allodynia and heat hyperalgesia.

SIGNOR-278690

Q8TEB7

P52565

1

polyubiquitination

up-regulates quantity by stabilization

0.266

We found that RhoGDIα and RhoGDIβ are ubiquitin E3 substrates of GRAIL. GRAIL uses nonlysine 48-ubiquitin linkage in polyubiquitinating RhoGDI. GRAIL was subsequently demonstrated to bind and ubiquitinate RhoGDI, although GRAIL-mediated ubiquitination of RhoGDI did not result in proteosomal degradation. Our data suggest that ubiquitination of RhoGDI by GRAIL does not result in proteolytic degradation. In fact, GRAIL activity appeared to increase RhoGDI stability.

SIGNOR-271622

O43521

O14965

0

phosphorylation

down-regulates quantity by destabilization

0.376

We observed that BimEL is phosphorylated by Aurora A early in mitosis and reversed by PP2A after mitotic exit. Aurora A phosphorylation stimulated binding of BimEL to the F-box protein beta-transducin repeat containing E3 ubiquitin protein ligase and promoted ubiquitination and degradation of BimEL.

SIGNOR-276248

Q13309

P11309

0

phosphorylation

up-regulates activity

0.34

We found that expression of Pim-1 increases the level of Skp2 through direct binding and phosphorylation of multiple sites on this protein. Along with known Skp2 phosphorylation sites including Ser(64) and Ser(72), we have identified Thr(417) as a unique Pim-1 phosphorylation target. Phosphorylation of Thr(417) controls the stability of Skp2 and its ability to degrade p27.

SIGNOR-259819

P61586

Q13618

0

ubiquitination

down-regulates quantity by destabilization

0.396

BACURDs form ubiquitin ligase complexes, which selectively ubiquitinate RhoA, with Cul3. Our studies reveal a previously unknown mechanism for controlling RhoA degradation and regulating RhoA function in various biological contexts, which involves a Cul3/BACURD ubiquitin ligase complex.

SIGNOR-264238

P41229

Q99814

0

transcriptional regulation

up-regulates quantity by expression

0.278

To this end, we confirm that KDM3A, KDM4B, KDM4C, KDM5B, KDM5C, and KDM62 are direct targets of HIF-1a while extent the list of known targets to KDM2A, KDM2B, KDM4D, KDM5A, and KDM6A. The results demonstrated that majority of the KDMs were similarly induced (KDM2A, KDM2B, KDM3A, KDM4B, KDM4C, KDM4D, KDM5A, KDM5B, KDM5C, KDM6B, and KDM7A) or repressed (KDM NO66 and KDM1A) by both HIF-1a and HIF-2a.

SIGNOR-271579

P48436

Q13464

0

phosphorylation

up-regulates

0.305

Rho kinase-dependent activation of sox9 in chondrocytes. In vitro, rock directly phosphorylated sox9 at ser(181), and the overexpression of rock or the activation of the rhoa pathway in sw1353 chondrosarcoma cells increased sox9(ser181) phosphorylation

SIGNOR-162643

Q9UBF6

Q8TB45

1

ubiquitination

down-regulates activity

0.299

SAG (Sensitive to Apoptosis Gene), also known as RBX2 (RING box protein 2), ROC2 (Regulator of Cullins 2), or RNF7 (RING Finger Protein 7), was originally cloned in our laboratory as a redox inducible antioxidant protein and later characterized as the second member of the RBX/ROC RING component of the SCF (SKP1-CUL-F-box Proteins) E3 ubiquitin ligase. by forming a complex with other components of the SCF E3 ligase, SAG promotes ubiquitination and degradation of a number of protein substrates, including c-JUN, DEPTOR, HIF-1α, IκBα, NF1, NOXA, p27, and procaspase-3, thus regulating various signaling pathways and biological processes.

SIGNOR-271449

P41180

P05771

0

phosphorylation

down-regulates activity

0.319

Expression of a mutant CaR in which the major PKC phosphorylation site is altered by substitution of alanine for threonine (T888A) eliminated oscillatory behavior, producing [Ca(2+)](i) responses almost identical to those produced by the wild type CaR exposed to PKC inhibitors. These results support a model in which phosphorylation of the CaR at the inhibitory threonine 888 by PKC provides the negative feedback needed to cause [Ca(2+)](i) oscillations mediated by this receptor.

SIGNOR-249176

Q14653

Q13043

0

phosphorylation

up-regulates activity

0.2

Beyond that, another investigation demonstrated that MST1 directly phosphorylated IRF3 at T75 and T253, which disrupted the dimerization of IRF3 and restrained RLRs and cGAS-mediated innate antiviral response.

SIGNOR-280145

Q13315

A1Z1Q3

1

phosphorylation

down-regulates activity

0.2

We found that MacroD2 is exported from the nucleus upon DNA damage and that this depends on the ATM-induced phosphorylation of the MacroD2 C-terminal IDR.|ATM activation leads to phosphorylation of the MacroD2 C-terminal region.

SIGNOR-279792

Q13426

P78527

0

phosphorylation

up-regulates activity

0.907

In response to ionizing radiation, ATM phosphorylates FBXW7 at serine 26 to recruit it to DNA double-strand break (DSB) sites, whereas activated DNA-PKcs phosphorylates XRCC4 at serines 325/326, which promotes binding of XRCC4 to FBXW7. SCF(FBXW7) E3 ligase then promotes polyubiquitylation of XRCC4 at lysine 296 via lysine 63 linkage for enhanced association with the Ku70/80 complex to facilitate NHEJ repair.

SIGNOR-277198

P08069

O00443

1

phosphorylation

up-regulates

0.275

Analysis of the ability of the full-length igfr and its mutant receptors described above to associate with phosphatidylinositol 3 kinase indicated that the association required ptk activity and tyrosine [?] Phosphorylation of the receptors and correlated well with their transforming activities

SIGNOR-32076

O00165

Q8TCJ0

0

ubiquitination

down-regulates quantity by destabilization

0.331

FBXO25 encodes an orphan F-box protein that determines the substrate specificity of the SCF (SKP1-CUL1-F-box)(FBXO25) ubiquitin ligase complex. An unbiased screen uncovered the prosurvival protein HCLS1-associated protein X-1 (HAX-1) as the bona fide substrate of FBXO25 that is targeted after apoptotic stresses. Protein kinase Cdelta (PRKCD) initiates this process by phosphorylating FBXO25 and HAX-1, thereby spatially directing nuclear FBXO25 to mitochondrial HAX-1.

SIGNOR-275563

P46934

O75896

1

ubiquitination

down-regulates quantity by destabilization

0.2

NEDD4 Degrades TUSC2 to Promote Glioblastoma Progression.|NEDD4 E3 ubiquitin ligase polyubiquitinates TUSC2 at residue K71, and the TUSC2-K71R mutant is resistant to NEDD4-mediated proteasomal degradation.

SIGNOR-278638

Q6J9G0

Q14457

1

phosphorylation

up-regulates activity

0.2

We also demonstrated that STYK1 elevated the serine phosphorylation of BECN1, thereby decreasing the interaction between BECN1 and BCL2. |The results indicated that the level of BECN1 S90 phosphorylation significantly increased after STYK1 overexpression, but not STYK1K147R mutant.|STYK1 promotes autophagy through enhancing the assembly of autophagy-specific class III phosphatidylinositol 3-kinase complex I

SIGNOR-264568

Q13115

P28482

1

dephosphorylation

down-regulates activity

0.762

Dephosphorylation and Inactivation of ERKs|A single protein kinase, MEK, activates ERK2 by phosphorylating threonine 183 and tyrosine 185

SIGNOR-248718

Q05655

P68431

1

phosphorylation

up-regulates activity

0.2

We identify protein kinase c-delta as the kinase responsible for h3t45ph in vitro and in vivo. Given the nucleosomal position of h3t45, we postulate that h3t45ph induces structural change within the nucleosome to facilitate dna nicking and/or fragmentation.

SIGNOR-185144

Q7Z2W7

P17612

0

phosphorylation

up-regulates activity

0.2

Using specific pharmacological and molecular tools combined with patch-clamp current recordings, we found that in heterologously expressed HEK-293 (human embryonic kidney) cells, TRPM8 channel is inhibited by the G(i) protein/adenylate cyclase (AC)/cAMP/protein kinase A (PKA) signaling cascade. We further identified the TRPM8 S9 and T17 as two key PKA phosphorylation sites regulating TRPM8 channel activity. the intracellular serine/threonine protein phosphatase 2A (PP2A) dephosphorylates TRPM8 Ser-9 and Thr-17 inhibiting the channel activity.

SIGNOR-273791

P60953

Q92502

0

gtpase-activating protein

down-regulates activity

0.511

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-260520

P21127

Q9UQ88

0

phosphorylation

up-regulates

0.305

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

SIGNOR-169628

P04626

P49327

1

phosphorylation

up-regulates activity

0.442

Conversely, HER2 directly phosphorylates and activates FASN, while it also promotes FASN gene expression ( xref ; xref ).|Conversely, HER2 directly phosphorylates and activates FASN, while it also promotes FASN gene expression.

SIGNOR-278399

P17655

P55085

1

cleavage

down-regulates activity

0.298

PAR1E and PAR2E (10 microM) were incubated in the presence of the different proteases | The enzymes were used at the following concentrations: 0.5 unit/mL thrombin, 2.5 nM trypsin, 20 nM plasmin, 20 nM cathepsin G, 20 nM elastase, 20 nM proteinase 3, and 2 units/mL calpain I and II|Protease-activated receptors (PARs) mediate cell activation after proteolytic cleavage of their extracellular amino terminus.|Mass spectrometry studies of PAR2E predicted activation of PAR2 by trypsin through cleavage at the Arg36-Ser37 site, no effect of thrombin, and inactivation of the receptor by plasmin, calpain and leukocyte elastase, cathepsin G, and proteinase 3

SIGNOR-263581

Q9H4B4

O96017

1

phosphorylation

up-regulates activity

0.66

Plk3 phosphorylates Chk2 at two residues, serine 62 (S62) and serine 73 (S73) in vitro, and this phosphorylation facilitates subsequent phosphorylation of Chk2 on T68 by ATM in response to DNA damage. When the Chk2 mutant construct GFP-Chk2 S73A (serine 73 mutated to alanine) is transfected into cells, it no longer associates with a large complex in vivo, and manifests a significant reduction in kinase activity.

SIGNOR-276051

Q14493

Q7L7L0

1

translation regulation

up-regulates quantity by expression

0.2

Synthesis of mature histone mRNA requires only a single processing reaction: an endonucleolytic cleavage between a conserved stem-loop and a purine-rich downstream element to form the 3' end. The stem-loop binding protein (SLBP) is required for processing, and following processing, histone mRNA is transported to the cytoplasm, where SLBP participates in translation of the histone mRNA|We used radiolabeled probes generated by PCR targeting the open reading frame (ORF) to detect histones H2A, H2B, H3, H4, and H1 and used 7SK snRNA as a loading control (Fig. 2A). The abundance of histone H2A, H2B, H3, and H4 mRNAs is reduced to 37% to 70% of control levels in the SLBP knockdown cells when compared to the C2 control.

SIGNOR-265409

P01584

Q04206

0

transcriptional regulation

down-regulates activity

0.555

Early Inhibition of IL-1 beta Expression by IFN-gamma Is Mediated by Impaired Binding of NF-kappa B to the IL-1 beta Promoter but Is Independent of Nitric Oxide|We report that IFN-γ suppressed bacterial RNA and LPS induced IL-1β transcription in primary murine macrophages

SIGNOR-251736

P51843

Q96EP0

0

monoubiquitination

up-regulates quantity by stabilization

0.437

RNF31 promotes monoubiquitination of DAX-1 in an RBR domain-dependent manner. In conclusion, our results suggest that the major DAX-1 modification observed in different experimental settings is likely to be monoubiquitination at one or more lysine residues (multiubiquitination) possibly located within the LBD of DAX-1. RNF31 stabilizes endogenous DAX-1.

SIGNOR-271786

P56945

P00519

0

phosphorylation

up-regulates activity

0.462

Abl silencing inhibits CAS mediated process and constriction in resistance arteries.|CAS phosphorylation was catalyzed by Abl in an in vitro study.

SIGNOR-279671

P48764

O00141

0

phosphorylation

up-regulates activity

0.433

The NHE3 activation by SGK1 is dependent on their combined interaction with NHERF2 and then phosphorylation at S663 of NHE3 by SGK1 ( xref , xref ).

SIGNOR-279112

Q16513

O15530

0

phosphorylation

up-regulates

0.705

It is shown that activation in vitro and in vivo involves the activation loop phosphorylation of prk1/2 by 3-phosphoinositide-dependent protein kinase-1 (pdk1) /pdk1 phosphorylates the prks at their conserved activation loop threonines (thr-774 and thr-816 for prk1 and prk2, respectively)

SIGNOR-76710

Q8IZQ8

P17252

0

phosphorylation

down-regulates activity

0.2

PKCalpha directly promoted the basal phosphorylation of endogenous myocardin at serine and threonine residues.

SIGNOR-279099

Q15831

Q13131

1

phosphorylation

up-regulates activity

0.599

The AMP-activated protein kinase (AMPK) is a critical regulator of energy balance at both the cellular and whole-body levels. Two upstream kinases have been reported to activate AMPK in cell-free assays, i.e., the tumor suppressor LKB1 and calmodulin-dependent protein kinase kinase.

SIGNOR-139297

Q99607

Q13315

0

phosphorylation

down-regulates activity

0.349

Elf4 is phosphorylated by Atm after gamma irradiation, leading to its degradation.|Thus, Atm promotes Elf4 protein degradation after gamma irradiation via phosphorylation at these sites.

SIGNOR-278466

Q9NQU5

Q16539

0

phosphorylation

up-regulates

0.2

The activation of pak6 by both p38 map kinase and mkk6 suggests that pak6 plays a role in the cellular response to stress-related signals.

SIGNOR-130979

P42575

P68400

0

phosphorylation

down-regulates

0.309

Here we show that protein kinase (pk) ck2 phosphorylates procaspase-2 directly at serine-157. When intracellular pkck2 activity is low or downregulated by specific inhibitors, procaspase-2 is dephosphorylated, dimerized, and activated in a piddosome-independent manner.

SIGNOR-140836

A8MYZ6

Q12857

0

transcriptional regulation

down-regulates quantity

0.2

By integrating transcriptomic profiling (RNA-seq) of Nfia- and Nfix-deficient GNPs with epigenomic profiling (ChIP-seq against NFIA, NFIB and NFIX, and DNase I hypersensitivity assays), we reveal that these transcription factors share a large set of potential transcriptional targets, suggestive of complementary roles for these NFI family members in promoting neural development

SIGNOR-268875

P28482

Q9HBH9

1

phosphorylation

up-regulates

0.6

We have identified a new subfamily of murine serine/threonine kinases, whose members, map kinase-interacting kinase 1 (mnk1) and mnk2, bind tightly to the growth factor-regulated map kinases, erk1 and erk2erk and p38 phosphorylate mnk1 and mnk2, which stimulates their in vitro kinase activity

SIGNOR-48338

P35568

P23458

0

phosphorylation

up-regulates activity

0.708

Janus kinase-dependent activation of insulin receptor substrate 1

SIGNOR-251343

P41221

Q14938

0

transcriptional regulation

down-regulates quantity

0.2

By integrating transcriptomic profiling (RNA-seq) of Nfia- and Nfix-deficient GNPs with epigenomic profiling (ChIP-seq against NFIA, NFIB and NFIX, and DNase I hypersensitivity assays), we reveal that these transcription factors share a large set of potential transcriptional targets, suggestive of complementary roles for these NFI family members in promoting neural development

SIGNOR-268889

P35790

Q9ULK5

1

phosphorylation

down-regulates activity

0.2

CKI\u03b5-dependent phosphorylation increases Stbm turnover at junctions, and thus promotes complex sorting, while phosphorylation of Dsh decreases its turnover.|Interestingly, CKI\u03b5 has been implicated in phosphorylation of both Stbm and Dsh.

SIGNOR-278925

P53350

O14641

1

phosphorylation

up-regulates

0.465

Dvl2 bound to and was phosphorylated at thr206 by a mitotic kinase, polo-like kinase 1 (plk1), and this phosphorylation was required for spindle orientation and stable microtubule (mt)-kt attachment

SIGNOR-167858

Q9H2B2

P45983

0

phosphorylation

up-regulates activity

0.411

JNK phosphorylates Syt 4 at Ser135 in vitro and in vivo.

SIGNOR-273673

Q15858

P10275

0

transcriptional regulation

up-regulates quantity by expression

0.2

In neuroblastoma ND7 cells, a nuclear interaction between the developmentally regulated transcription factor Brn-3a and AR resulted in a complex which bound to multiple elements within the promoter region of SCN9A (Nav1.7) and upregulated channel expression.

SIGNOR-253466

P17612

Q9UL62

1

phosphorylation

down-regulates quantity

0.2

Together, these results suggest that TRPC5 is directly phosphorylated by G(s)/cAMP/PKA at positions S794 and S796. These inhibitory effects were blocked by the protein kinase A (PKA) inhibitors, KT-5720 and H-89, as well as by two point mutations at consensus PKA phosphorylation sites on TRPC5 (S794A and S796A).

SIGNOR-277823

P12830

O60729

0

dephosphorylation

up-regulates activity

0.313

Cdc14B activates APC/C Cdh1 after DNA damage in G2.|Importantly, after DNA damage, thein vivo phosphorylation of wild type Cdh1 - but not that of Cdh1 (4xA) - increased after Cdc14B silencing (XREF_FIG), indicating that in response to genotoxic stress, Cdc14B dephosphorylates Cdh1 on the four sites phosphorylated by Cdk2.

SIGNOR-277017

Q00535

P06241

0

phosphorylation

up-regulates activity

0.608

Constitutively active Fyn phosphorylated Tyr15 of Cdk5. Fyn Facilitates Kinase Activity of Cdk5 Via Tyr15 Phosphorylation

SIGNOR-251156

Q05655

P05230

1

phosphorylation

up-regulates quantity

0.2

Translocated FGF1 can be phosphorylated by PKC\u03b4 on serine 130.

SIGNOR-278451

P35900

P49137

0

phosphorylation

up-regulates activity

0.2

P38 phosphorylates the type II keratin, K8 at Ser73, whereas MK2 phosphorylates the binding partners K18 at Ser52 and K20 at Ser13.

SIGNOR-263071

P10912

Q13163

1

phosphorylation

up-regulates activity

0.2

The MEK5-dependent activation of ERK5 promotes binding of the transcription factor SP1 to the promoter of the genes encoding the transcription factors Klf2 and Klf4, leading to their increased abundance. Subsequently, Klf2 and Klf4 bind to the Npnt promoter and induce the production of nephronectin during myoblast fusion

SIGNOR-255452

P35638

P68400

0

phosphorylation

down-regulates activity

0.344

CHOP transcription factor phosphorylation by casein kinase 2 inhibits transcriptional activation. | The serine to alanine substituted site CHOP mutant was not phosphorylated by CK2, indicating that serines 14–15 and 30–31 of CHOP are the CK2 phosphoacceptor sites

SIGNOR-250850

P36894

Q99717

1

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

Q04721

P49841

0

phosphorylation

down-regulates activity

0.481

We show that gsk-3beta directly binds at c-terminal of the notch2 ankyrin repeats and phosphorylates thr-2068 and/or ser-2070, thr-2074, and thr-2093.

SIGNOR-101570

P00519

Q92769

1

phosphorylation

up-regulates quantity by stabilization

0.285

C-Abl stabilizes HDAC2 levels by tyrosine phosphorylation repressing neuronal gene expression in Alzheimer's disease.

SIGNOR-260928

P06730

Q9BUB5

0

phosphorylation

up-regulates

0.779

Mnk1 and mnk2 regulate protein synthesis by phosphorylating the initiation factor eif4e.

SIGNOR-166646

P24941

O15350

1

phosphorylation

down-regulates activity

0.575

Cyclin-dependent kinases phosphorylate p73 at threonine 86 in a cell cycle-dependent manner and negatively regulate p73.Furthermore, cyclin a/cdk1/2, cyclin b/cdk1/2, and cyclin e/cdk2 complexes can phosphorylate multiple p73 isoforms in vitro at threonine 86.

SIGNOR-99746

O15162

P12931

0

phosphorylation

up-regulates activity

0.476

Plscr1 is phosphorylated by c-src, within the tandem repeat sequence 68vynqpvynqp77.|The EGF-mediated Interaction between PLSCR1 and Shc Requires Phosphorylation of Tyr69 and Tyr74 in PLSCR1

SIGNOR-103773

Q6IAA8

Q05086

0

ubiquitination

down-regulates quantity by destabilization

0.2

Ube3a regulates mTORC1 signaling by targeting p18, a subunit of the Ragulator. Ube3a ubiquinates p18, resulting in its proteasomal degradation, and Ube3a deficiency in the hippocampus of AS mice induces increased lysosomal localization of p18 and other members of the Ragulator-Rag complex, and increased mTORC1 activity

SIGNOR-256145

O60346

P49841

0

phosphorylation

down-regulates

0.353

In addition, we show that the beta-trcp-mediated degradation requires phosphorylation of phlpp1 by casein kinase i and glycogen synthase kinase 3beta (gsk-3beta), and activation of the phosphatidylinositol 3-kinase/akt pathway suppresses the degradation of phlpp1 by inhibiting the gsk-3beta activity.

SIGNOR-188330

Q06187

P07948

0

phosphorylation

up-regulates

0.545

Phosphorylation at y551 requires lyn kinase activity, indicating that y551 is a transphosphorylation site \ this transphosphorylation at y551 is followed by phosphorylation at a second site, which is dependent on btk catalytic activity.

SIGNOR-41607

P27540

P04798

1

transcriptional regulation

up-regulates quantity by expression

0.646

Kaempferol proved to be capable of inhibiting binding of agonist and agonist-induced formation of the AHR/ARNT DNA-binding complex and upregulation of the AHR target gene, CYP1A1.

SIGNOR-259910

Q96I59

P18848

0

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-269423

P05023

P28482

0

phosphorylation

down-regulates activity

0.519

Parathyroid hormone (PTH) inhibits Na+,K+-ATPase activity through protein kinase C- (PKC) and extracellular signal-regulated kinase- (ERK) dependent pathways and increases serine phosphorylation of the α1-subunit. These results suggest that PTH regulates Na(+),K(+)-ATPase by PKC and ERK-dependent alpha(1)-subunit phosphorylation and that the phosphorylation requires the expression of a serine at the 11 position of the Na(+),K(+)-ATPase alpha(1)-subunit.

SIGNOR-262940

O14745

Q15418

0

phosphorylation

up-regulates activity

0.33

In summary, these results demonstrate that Ras-RSK1 signaling promotes nuclear localization of EBP50.|Specifically, RSK1 phosphorylates EBP50 at threonine 156 (T156) residue in a cell cycle dependent manner, which is important for nuclear translocation of EBP50 to facilitate cellular proliferation and transformation.

SIGNOR-278290

Q96J02

Q9HBA0

1

ubiquitination

down-regulates activity

0.377

AIP4 ubiquitin ligase is involved in the ubiquitination of both TRPV4 and TRPC4.Ubiquitination of TRPV4 is dramatically increased by the HECT (homologous to E6-AP carboxyl terminus)-family ubiquitin ligase AIP4 without inducing degradation of this channel. Instead, AIP4 promotes the endocytosis of TRPV4 and decreases its amount at the plasma membrane.

SIGNOR-272625

O95684

Q15691

1

relocalization

up-regulates

0.2

Fop also binds to eb1 and is required for localizing eb1 to the centrosome

SIGNOR-142400

Q9UQD0

Q13557

0

phosphorylation

up-regulates activity

0.281

CaMKII enhances voltage-gated sodium channel Nav1.6 activity and neuronal excitability|mmobilized peptide arrays and nanoflow LC-electrospray ionization/MS of Nav1.6 reveal potential sites of CaMKII phosphorylation, specifically Ser-561 and Ser-641/Thr-642 within the first intracellular loop of the channel.

SIGNOR-275792

P11474

Q9H0X6

1

transcriptional regulation

up-regulates quantity by expression

0.2

Furthermore, RNF208 was induced by 17β-estradiol (E2) treatment in an estrogen receptor alpha (ΕRα)-dependent manner

SIGNOR-269052

P43003

O00141

0

phosphorylation

up-regulates activity

0.415

Site‐directed mutagenesis of the SGK1 phosphorylation sites in the Nedd4‐2 protein (S382A,S468ANedd4‐2) and in the EAAT1 protein (T482AEAAT1, T482DEAAT1) significantly blunts the effect of S422DSGK1. Introduction of a negative charge at the SGK phosphorylation site in the EAAT1 protein leads to a strong stimulation of the carrier, whereas replacement with alanine markedly decreases the EAAT1‐mediated current. These observations suggest that SGK1 exerts its effect not only by phosphorylation of Nedd4‐2 but also by phosphorylation of EAAT1.

SIGNOR-263075

Q13315

Q96P70

1

phosphorylation

up-regulates activity

0.2

In line with our previous results, IR exposure induced the nuclear accumulation of RanBP9, which was prevented by ATM inhibition using KU-55933.|Taken together these data indicate that RanBP9 is a novel target of ATM and that ATM phosphorylates at least two different residues (S181 and S603) of RanBP9 following IR exposure.

SIGNOR-278910

Q7Z434

Q14258

0

polyubiquitination

down-regulates quantity by destabilization

0.77

We report here that RLR activation triggers MAVS ubiquitination on lysine 7 and 10 by the E3 ubiquitin ligase TRIM25 and marks it for proteasomal degradation concomitantly with downstream signaling.

SIGNOR-272042

Q13315

Q15109

1

phosphorylation

up-regulates activity

0.2

RAGE is phosphorylated at Serine 376 and Serine 389 by the ATM kinase and is recruited to the site of DNA-DSBs via an early DNA damage response.

SIGNOR-278907

P18754

P06493

0

phosphorylation

up-regulates activity

0.504

We show here that Cdc2 kinase phosphorylates the serines located in or near the nuclear localization signal (NLS) of hum an RCC1, the nucleotide exchange factor for Ran. This phosphorylation is necessary for RCC1 to generate RanGTP on mitotic chromosomes in mammalian cells, which in turn is required for spindle assembly and chromosome segregation. However, when both S2 and S11 were simultaneously mutated to As, the resulting 6His-RCC1S2,11A failed to be phosphorylated, whereas all of the other double mutants were phosphorylated (Fig. 1C). As expected, mutating all four sites to As (the 6His-RCC1S2,11,387A-T274A) also blocked phosphorylation (Fig. 1C).

SIGNOR-262704

O76050

O76083

1

polyubiquitination

down-regulates quantity by destabilization

0.2

Neuralized family member NEURL1 is a ubiquitin ligase for the cGMP-specific phosphodiesterase 9A. We also demonstrate that NEURL1 can promote polyubiquitination of PDE9A that leads to its proteasome-mediated degradation mainly via lysine residue K27 of ubiquitin.

SIGNOR-272305