GleghornLab/Signor_2class · Datasets at Hugging Face

IdA string	IdB string	labels int64	mechanism string	effect string	score float64	sentence string	signor_id string
P49841	Q02750	0	phosphorylation	up-regulates activity	0.343	In vitro kinase assay was carried out using a recombinant human active mek1 and we found that gsk-3beta was phosphorylated on tyr(216) by this kinase in a dose- and time-dependent manner. Further, the pretreatment of fibroblasts with u0126 inhibited serum-induced nuclear translocation of gsk-3beta. These results suggested that mek1/2 induces tyrosine phosphorylation of gsk-3beta and this cellular event might induce nuclear translocation of gsk-3beta.	SIGNOR-236622
P51692	P18031	0	dephosphorylation	down-regulates activity	0.676	A Cytosolic Protein-tyrosine Phosphatase PTP1B Specifically Dephosphorylates and Deactivates Prolactin-activated STAT5a and STAT5b	SIGNOR-248429
P05231	O95644	0	transcriptional regulation	up-regulates quantity by expression	0.415	The calcineurin/nuclear factor of activated T cells (NFAT) signaling pathway has been found to play a role in regulating growth and differentiation in several cell types. However, the functional significance of NFAT in the vasculature is largely unclear. Here we show that NFATc1, NFATc3, and NFATc4 are expressed in human myometrial arteries. \|Chronic inhibition of NFAT significantly reduced IL-6 production in intact myometrial arteries and inhibited cell proliferation in vascular smooth muscle cells cultured from explants from the same arteries.	SIGNOR-251730
Q9BXW9	Q13535	0	phosphorylation	up-regulates	0.673	In the present study, we identify two novel dna damage-inducible phosphorylation sites on fancd2, threonine 691 and serine 717. Atr phosphorylates fancd2 on these two sites, thereby promoting fancd2 monoubiquitination and enhancing cellular resistance to dna cross-linking agents	SIGNOR-149305
P07195	O14965	0	phosphorylation	up-regulates activity	0.2	Aurora-A-mediated phosphorylation of LDHB serine 162 significantly increases its activity in reducing pyruvate to lactate, which efficiently promotes NAD+ regeneration, glycolytic flux, lactate production and bio-synthesis with glycolytic intermediates.	SIGNOR-277493
Q92630	O14746	1	phosphorylation	down-regulates activity	0.444	Dyrk2 phosphorylates TERT protein, a catalytic subunit of telomerase.\|In this study, we found that dual-specificity tyrosine-(Y)-phosphorylation-regulated kinase 2 (Dyrk2) negatively regulates telomerase activity.	SIGNOR-279611
Q9BTM1	Q86Y13	0	monoubiquitination	up-regulates activity	0.2	2A-HUB catalyzes monoubiquitination of H2A at lysine 119, functioning as a combinatoric component of the repression machinery required for specific gene regulation programs. Thus, 2A-HUB mediates a selective repression of a specific set of chemokine genes in macrophages, critically modulating migratory responses to TLR activation. H2A monoubiquitination acts to prevent FACT recruitment at the transcriptional promoter region, blocking RNA polymerase II release at the early stage of elongation.	SIGNOR-271763
O75582	P54253	1	phosphorylation	up-regulates quantity by stabilization	0.26	In summary, the data from the cell based screen, biochemical studies and genetic interactions strongly suggest that MSK1 phosphorylates ATXN1 and regulates its stability.	SIGNOR-279109
Q5SQI0	O43318	0	phosphorylation	up-regulates activity	0.2	Here we report TGF-beta-activated kinase 1 (TAK1) as a key activator of alphaTAT1. TAK1 directly interacts with and phosphorylates alphaTAT1 at Ser237 to critically enhance its catalytic activity	SIGNOR-272243
P24941	Q16584	1	phosphorylation	up-regulates activity	0.2	Using in vitro kinase assays and phosphomutants, we determined that CDK1 phosphorylates MLK3 on Ser548 and decreases MLK3 activity during mitosis, whereas CDK2 phosphorylates MLK3 on Ser770 and increases MLK3 activity during G1/S and G2 phases.	SIGNOR-277604
Q6IMN6	P01178	1	post transcriptional regulation	up-regulates quantity by stabilization	0.2	Transcriptional and post-transcriptional regulation of oxytocin and vasopressin gene expression by CREB3L1 and CAPRIN2\|Altogether, the data indicate that CAPRIN2 binds Oxt mRNA \|Therefore, we propose that CAPRIN2 facilitates post-transcriptional modifications that increase Oxt transcript stability.	SIGNOR-268556
P06493	Q06830	1	phosphorylation	down-regulates	0.35	Peroxiredoxin (prx) i is a member of the peroxiredoxin family of peroxidases and contains a consensus site (thr(90)-pro-lys-lys) for phosphorylation by cyclin-dependent kinases (cdks). This protein has now been shown to be phosphorylated specifically on thr(90) by several cdks, including cdc2, in vitro. Phosphorylation of prx i on thr(90) reduced the peroxidase activity of this protein by 80%.	SIGNOR-87097
Q8N752	P35222	1	phosphorylation	down-regulates	0.508	We show that a complex of axin and casein kinase i (cki) induces beta-catenin phosphorylation at a single site: serine 45 (s45).	SIGNOR-87430
O96017	Q9NY61	1	phosphorylation	up-regulates quantity by stabilization	0.358	Three putative Chk2 phosphorylation sites (Stevens et al., 2003) are present in Che-1 at resides Ser141, Ser474, and Ser508. Thus, we performed in vitro Chk2 kinase assays utilizing the GST-Che-1 fusion peptides spanning these residues as substrates.\| Taken together, these results indicate that Chk2 phosphorylates Che-1 and this phosphorylation contributes to increase Che-1 stability.	SIGNOR-264416
P27361	O15525	1	phosphorylation	up-regulates quantity	0.368	By contrast, MAFG-S124A was not phosphorylated, indicating that ERK1 phosphorylates MAFG at S124.\|Notably, cotransfection of ERK1 increased total levels of wild-type MAFG and MAFG-T3A but not MAFG-S124A, indicating that phosphorylation increased MAFG stability.	SIGNOR-280027
P24941	P03372	1	phosphorylation	up-regulates	0.477	The pi3k/akt pathway is necessary to activate cdk2, which phosphorylates eralphaser294, and mediates the binding between pin1 and eralpha	SIGNOR-200867
P51812	Q14790	1	phosphorylation	down-regulates quantity by destabilization	0.369	The ribosomal S6 kinase 2 (RSK2) is a member of the p90 ribosomal S6 kinase (p90RSK) family of proteins and plays a critical role in proliferation, cell cycle, and cell transformation. Here, we report that RSK2 phosphorylates caspase-8, and Thr-263 was identified as a novel caspase-8 phosphorylation site. In addition, we showed that EGF induces caspase-8 ubiquitination and degradation through the proteasome pathway, and phosphorylation of Thr-263 is associated with caspase-8 stability.	SIGNOR-272997
P10523	P46934	0	polyubiquitination	down-regulates quantity by destabilization	0.373	Here we report that NEDD4-1, a HECT domain-containing E3 ubiquitin ligase, binds via its HECT domain directly with SAG's C-terminal RING domain and ubiquitylates SAG for proteasome-mediated. We also found that SAG bridges NEDD4-1 via its C-terminus and CUL-5 via its N-terminus to form a NEDD4-1/SAG/CUL-5 tri-complex. Biologically, NEDD4-1 overexpression sensitizes cancer cells to etoposide-induced apoptosis by reducing SAG levels through targeted degradation. Thus, SAG is added to a growing list of NEDD4-1 substrates and mediates its biological function. degradation.	SIGNOR-272843
P08581	P23467	0	dephosphorylation	down-regulates	0.364	Ptp1b and shp-2 are bound to the c-met receptor to control its activity. Although the binding of ptp1b increases when there is a decrease in c-met activation and acts as a negative regulator of the receptor, the increased binding and phosphorylation of shp-2 coincide with maximal stimulation of c-met, acting as a positive regulator.	SIGNOR-139560
P50552	Q13976	0	phosphorylation	down-regulates activity	0.735	Vertebrate Ena/VASP proteins are phosphorylated by PKA, as well as PKG, and the phosphorylation is required for full function in a number of cellular contexts	SIGNOR-268289
P06493	Q13586	1	phosphorylation	down-regulates	0.345	Stim1 is phosphorylated during mitosis. Removal of ten mpm-2 recognition sites by truncation at amino acid 482 abolished mpm-2 recognition of mitotic stim1, and significantly rescued stim1 rearrangement and soce response in mitosis. We identified ser 486 and ser 668 as mitosis-specific phosphorylation sites, and stim1 containing mutations of these sites to alanine also significantly rescued mitotic soce.	SIGNOR-189017
Q04206	P60510	0	dephosphorylation	up-regulates activity	0.361	Suppression of MEK/ERK signaling pathway enhances cisplatin-induced NF-kappaB activation by protein phosphatase 4-mediated NF-kappaB p65 Thr dephosphorylation	SIGNOR-248549
P13224	P17612	0	phosphorylation	down-regulates activity	0.312	Platelet glycoprotein Ib beta is phosphorylated on serine 166 by cyclic AMP-dependent protein kinase. phosphorylation of this residue may contribute to the inhibitory actions of cyclic AMP by inhibiting collagen-induced polymerization of actin.	SIGNOR-249986
O14733	O43379	0	relocalization	up-regulates activity	0.294	In the WT brain, the WDR62 scaffold organizes a protein complex including MEKK3, MKK4/7, and JNK1 to control NPC development during corticogenesis	SIGNOR-271716
P07101	P51812	0	phosphorylation	up-regulates	0.267	Mitogen-activated protein-kinase (map) kinase-activated protein kinases 1 and 2 (mapkap kinase-1, mapkap kinase-2), were found to phosphorylate bacterially expressed human tyrosine hydroxylaserecombinant human tyrosine hydroxylase (hth1) was found to be phosphorylated by mitogen and stress-activated protein kinase 1 (msk1) at ser40 and by p38 regulated/activated kinase (prak) on ser19. Phosphorylation by msk1 induced an increase in vmax	SIGNOR-34682
P55211	Q13627	0	phosphorylation	down-regulates activity	0.388	Depletion of DYRK1A from human cells by short interfering RNA inhibits the basal phosphorylation of caspase 9 at an inhibitory site, Thr125. DYRK1A-dependent phosphorylation of Thr125 is also blocked by harmine, confirming the use of this beta-carboline alkaloid as a potent inhibitor of DYRK1A in cells.\|When co-expressed in cells, DYRK1A interacts with caspase 9, strongly induces Thr125 phosphorylation and inhibits caspase 9 auto-processing.	SIGNOR-279326
P31749	P99999	1	phosphorylation	down-regulates activity	0.465	Finally, we propose that pro-survival kinase Akt (protein kinase B) is a likely mediator of the S47 phosphorylation of Cytc in the brain.	SIGNOR-277237
P31749	Q16763	1	phosphorylation	up-regulates quantity by stabilization	0.437	Mechanistically, Akt1 physically interacted with and phosphorylated UBE2S at Thr 152, enhancing its stability by inhibiting proteasomal degradation.	SIGNOR-265078
P25098	O76070	1	phosphorylation	down-regulates activity	0.2	GRK-mediated phosphorylation inhibits synuclein's interaction with both phospholipids and PLD2. Mutation of Ser124 dramatically inhibits γ-synuclein phosphorylation by GRK2	SIGNOR-251204
Q14674	P53350	0	phosphorylation	down-regulates activity	0.772	Although mutation of serine 1126 and threonine 1346 to alanine had no effect (lanes 2 and 5), additional mutation of threonine 1363 and serine 1399 rendered separase almost completely resistant to phosphorylation (lane 3). Serine 1399 seems to be the one residue within this large separase fragment that is most efficiently phosphorylated by polo-like kinase, because a corresponding point mutation was sufficient to reduce the labeling by 80% compared with wild type (lane 6).	SIGNOR-276082
Q15797	Q04771	0	phosphorylation	up-regulates activity	0.703	ALK2 receptor specifically interacts with and phosphorylates Smad1 protein. ALK2 Activates Smad1 and Induces BMP-specific Signals. Biochemical analysis revealed that constitutively active ALK2 associated with and phosphorylated Smad1 on the COOH-terminal SSXS motif	SIGNOR-251439
Q92995	P11441	1	deubiquitination	up-regulates activity	0.61	USP13 and gp78 control ubiquitination of Ubl4A.These data suggest that USP13 and gp78 play antagonizing roles in regulation of Ubl4A ubiquitination: While gp78 assembles ubiquitin chains on Ubl4A, USP13 antagonizes this activity to limit Ubl4A ubiquitination.Ubiquitination of Ubl4A preferentially occurs on Lys48. We identify the Bag6 cofactor Ubl4A as a shared substrate of gp78 and USP13. USP13 depletion is associated with hyper-ubiquitination of Ubl4A and altered interaction between the Bag6 complex and its co-chaperone SGTA. Because the interaction of Ubl4A with SGTA is mediated by positively-charged residues in Ubl4A including Lys48 (Chartron et al., 2012; Xu et al., 2012), which happens to be the major ubiquitination site, the simplest model to explain reduced Bag6-SGTA interaction in USP13 knockdown cells is that ubiquitin conjugates on Ubl4A sterically hinder SGTA binding.	SIGNOR-272857
P45983	Q96P20	1	phosphorylation	up-regulates activity	0.369	Ethanol induced JNK1 phosphorylation activated the NLRP3 inflammasome that induced caspase-1 dependent mitophagy inhibition, thereby exacerbating ROS accumulation and causing cell death.\|However, recent studies suggested that Ser 194 phosphorylation of NLRP3 was essential for the control of inflammasome activation and that JNK1 directly phosphorylates NLRP3, which stimulates the self-association and oligomerization of NLRP3 [ xref , xref ].	SIGNOR-280034
O15169	Q9H2K2	0	ADP-ribosylation	down-regulates quantity by destabilization	0.705	Together, these findings are consistent with the hypothesis that TNKS promotes the ubiquitination and degradation of axin, which may be mediated, at least in part, through the direct PARsylation of axin.	SIGNOR-263378
Q12933	Q8IUC6	1	polyubiquitination	up-regulates	0.433	Here, we show that the TRAF family proteins directly bind TICAM-1 and demonstrate that TRAF2 and TRAF6 bind different sites of the N-terminal TICAM-1 and accelerate its polyubiquitination. we speculate that polyubiquitination of TICAM-1 by TRAF2 and TRAF6 is required for TICAM-1 to induce IRF-3 and NF-κB activation. This is supported by the observation that polyubiquitination of TICAM-1 was required for TRAF3-binding to TICAM-1	SIGNOR-271427
P09211	P05129	0	phosphorylation	up-regulates activity	0.2	Peptide phosphorylation analyses and both phosphorylation and enzyme kinetic studies with GSTP1 proteins mutated at candidate amino acid residues established Ser-42 and Ser-184 as putative phospho-acceptor residues for both kinases in the GSTP1 protein. Together, these findings show PKA- and PKC-dependent phosphorylation as a significant post-translational mechanism of regulation of GSTP1 function. Together, these results further support S42 and S184 as major phosphor-acceptor residues for PKA and PKC and suggest that the increased activity of the phospho-GSTP1 was not simply a consequence of the negative charge introduced in the GSTP1 protein by the phosphate group.All eight PKC isoforms, PKC-α, PKC-βI, PKC-βII, PKC-ε, PKC-γ, PKC-η, and PKC-ζ phosphorylated the GSTP1 protein efficiently	SIGNOR-276018
P35558	Q86UZ6	0	transcriptional regulation	up-regulates quantity by expression	0.2	We identified LIF/ZBTB46 signalling as a key promoter of metabolic reprogramming and NE differentiation of PCa cells through interactions with PCK1. We showed that ZBTB46 directly upregulates the expression of PCK1 and NE marker gene through activation of LIF signalling.	SIGNOR-277987
Q9NS56	P04637	1	ubiquitination	down-regulates	0.461	Plk1-mediated phosphorylation of topors regulates p53 stabilityherein, we have identified topoisomerase i-binding protein (topors), a p53-binding protein, as a plk1 target. We show that plk1 phosphorylates topors on ser(718) in vivo. Significantly, expression of a plk1-unphosphorylatable topors mutant (s718a) leads to a dramatic accumulation of p53 through inhibition of p53 degradation. Topors is an ubiquitin and small ubiquitin-like modifier ubiquitin-protein isopeptide ligase (sumo e3) ligase. Plk1-mediated phosphorylation of topors inhibits topors-mediated sumoylation of p53, whereas p53 ubiquitination is enhanced, leading to p53 degradation.	SIGNOR-185848
P24941	Q07817	1	phosphorylation	up-regulates activity	0.496	Our findings show that Cdk2 phosphorylation of Bcl-xL at Ser73, but not the Bcl-xL cleavage products, is necessary and sufficient to induce cell death.	SIGNOR-278242
P63151	P30291	1	dephosphorylation	up-regulates quantity by stabilization	0.385	Knockout of FAM122A results in activation of PP2A-B55α, a phosphatase that dephosphorylates the WEE1 protein and rescues WEE1 from ubiquitin-mediated degradation. in tumor cells with oncogene-driven replication stress, CHK1 can directly phosphorylate FAM122A, leading to activation of the PP2A-B55α phosphatase and increased WEE1 expression.	SIGNOR-266381
P42574	P55212	1	cleavage	up-regulates	0.619	Caspase-3 is required for the activation of caspases 6	SIGNOR-64179
P28482	Q9BUB5	1	phosphorylation	up-regulates	0.594	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 toward a substrate, eukaryotic initiation factor-4e (eif-4e).	SIGNOR-48298
Q9UI95	Q92733	0	relocalization	up-regulates	0.496	We found that the human papillary renal cell carcinoma-associated proteinprccinteracts with the cell cycle control proteinmad2b, and translocates this protein to the nucleus where it exerts its mitotic checkpoint function.	SIGNOR-126516
P37231	P17676	0	transcriptional regulation	up-regulates quantity	0.729	Induction of C/EBP beta DNA-binding activity in NIH-3T3 beta 2 cells exposed to dexamethasone in the presence of insulin and fetal bovine serum activates the expression of an adipocyte-specific nuclear hormone receptor, PPAR gamma, that stimulates the conversion of these fibroblasts into committed preadipocytes	SIGNOR-255730
P55317	P10275	1	transcriptional regulation	down-regulates quantity by repression	0.766	FOXA1 directly inhibits AR expression and thus the transcription of its target genes. FOXA1 inhibits AR gene expression in prostate cancer. oss of FOXA1 may lead to androgen-independent AR signaling and thus castration-resistant prostate cancer progression. Indeed, we have recently reported that FOXA1 is downregulated in CRPC	SIGNOR-251541
O14641	P60484	0	dephosphorylation	down-regulates activity	0.318	This showed that while both PTEN WT and the lipid phosphatase-inactive G129E mutant suppressed phosphorylation of DVL2 on serine 143 that accumulated upon PTEN knockdown, the C124S and Y138L mutants did not .\|Finally, it is important to point out that while our studies show that PTEN can directly dephosphorylate DVL2 in vitro, it is possible that regulation of serine 143 phosphorylation of DVL2 by PTEN in cells may require additional protein factors, or post-translational modifications.	SIGNOR-277035
Q86YJ5	P15151	1	ubiquitination	down-regulates quantity by destabilization	0.2	MARCH9, a member of the RING-CH family of transmembrane E3 ubiquitin ligases, down-regulates CD4, major histocompatibility complex-I (MHC), and ICAM-1 in lymphoid cells. To identify novel MARCH9 substrates, we used high throughput flow cytometry and quantitative mass spectrometry by stable isotope labeling by amino acids in cell culture (SILAC) to determine the differential expression of plasma membrane proteins in a MARCH9-expressing B cell line. This combined approach identified 13 potential new MARCH9 targets.	SIGNOR-271530
Q9UI32	P23771	0	transcriptional regulation	up-regulates quantity by expression	0.332	Thus, GATA3 contributes to the elevated expression of GLS2 in luminal-subtype breast cancers.	SIGNOR-268034
O14920	Q99759	0	phosphorylation	up-regulates activity	0.569	Genetic analysis showed that MEKK3, which is thought to activate IKK2 through phosphorylation (Yang et al., 2001), is necessary for TNF-alpha-induced NF-kappaB activation.\|Our results also suggest that IKK2 is phosphorylated on S177 and S181 on its activation loop by MEKK3.	SIGNOR-279468
Q06187	P16885	1	phosphorylation	up-regulates	0.778	By measuring the ability of human plcgamma2 to restore calcium responses to the b-cell receptor stimulation or oxidative stress in a b-cell line (dt40) deficient in plcgamma2, we have demonstrated that two tyrosine residues, tyr(753) and tyr(759), were important for the plcgamma2 signaling function.Of the two kinases that previously have been proposed to phosphorylate plcgamma2, btk, and syk, purified btk had much greater ability to phosphorylate recombinant plcgamma2 in vitro, whereas syk efficiently phosphorylated adapter protein blnk.	SIGNOR-111069
O43379	O14733	1	relocalization	up-regulates activity	0.294	In the WT brain, the WDR62 scaffold organizes a protein complex including MEKK3, MKK4/7, and JNK1 to control NPC development during corticogenesis	SIGNOR-271716
O00409	Q9P1W9	1	transcriptional regulation	down-regulates quantity by repression	0.297	CHES1/FOXN3 regulates cell proliferation by repressing PIM2 and protein biosynthesis.	SIGNOR-261607
P35240	Q13153	0	phosphorylation	down-regulates	0.645	Merlin contains a c-terminal serine 518, which is phosphorylated both by p21-activated kinase (pak) and protein kinase a (pka) (shaw et al., 2001;kissil et al., 2002;xiao et al., 2002;alfthan et al., 2004). Phosphorylation at this site is predicted to result in a more open conformation incapable of inhibiting cell growth,	SIGNOR-159764
P19174	O60260	0	ubiquitination	down-regulates quantity	0.2	In order to address the functional role of parkin ubiquitination of PLCgamma1, we investigated PLC activity in human neuroblastoma SH-SY5Y cell lines stably transfected with either WT, or mutant R42P or G328E parkin.\|WT parkin expression significantly reduced the levels of PLCgamma1 in human neuroblastoma.	SIGNOR-278592
Q8N653	P01116	1	ubiquitination	down-regulates activity	0.25	By trapping LZTR1 complexes from intact mammalian cells, we identified the guanosine triphosphatase RAS as a substrate for the LZTR1-CUL3 complex. Ubiquitome analysis showed that loss of Lztr1 abrogated Ras ubiquitination at lysine-170. LZTR1-mediated ubiquitination inhibited RAS signaling by attenuating its association with the membrane.	SIGNOR-269068
P68400	P35579	1	phosphorylation	up-regulates	0.34	In egf-stimulated cells, the myosin-iia heavy chain is phosphorylated on the casein kinase 2 site (s1943)	SIGNOR-155987
Q9NYL2	P52566	1	phosphorylation	down-regulates activity	0.2	In the present study, we provide evidence that ZAK serves as a RhoGDIbeta kinase, and demonstrate the phosphorylation of RhoGDIbeta by ZAK in vitro, as well as the physical association between ZAK and RhoGDIbeta.\|These two proteins could negatively regulate one another such that ZAK suppresses RhoGDIbeta functions through phosphorylation and RhoGDIbeta counteracts the effects of ZAK by physical interaction.	SIGNOR-279633
P07954	P78527	0	phosphorylation	up-regulates activity	0.2	We show that exposure to ionizing radiation induces DNA-PK-dependent phosphorylation of nuclear fumarase at Thr 236, which leads to an interaction between fumarase and the histone variant H2A.Z at DNA double-strand break (DSB) regions.	SIGNOR-266349
P08253	Q9NPA2	0	cleavage	up-regulates activity	0.375	Direct activation of pro-matrix metalloproteinase-2 by leukolysin/membrane-type 6 matrix metalloproteinase/matrix metalloproteinase 25 at the asn(109)-Tyr bond. Leukolysin Cleaves ProMMP-2 at Asn66-Leu and Asn109-Tyr.	SIGNOR-256345
P31751	Q01860	1	phosphorylation	up-regulates quantity by stabilization	0.255	Here we show that in ECCs, Akt phosphorylated the master pluripotency factor Oct4 at threonine 235, and that the levels of phosphorylated Oct4 in ECCs correlated with resistance to apoptosis and tumorigenic potential. Phosphorylation of Oct4 increased its stability and facilitated its nuclear localization and its interaction with Sox2, which promoted the transcription of the core stemness genes POU5F1 and NANOG.	SIGNOR-242097
P19838	Q96FX8	0	ubiquitination	down-regulates quantity	0.2	We identify KPC1 as the Ub ligase (E3) that binds to the ankyrin repeats domain of p105, ubiquitinates it, and mediates its processing both under basal conditions and following signaling	SIGNOR-255843
P12931	P52565	1	phosphorylation	down-regulates	0.399	We show here that src kinase binds and phosphorylates rhogdi both in vitro and in vivo at tyr156. analysis of rho gtpase-rhogdi complexes using in vitro assays of complexation and in vivo by coimmunoprecipitation analysis indicates that src-mediated phosphorylation of tyr156 causes a dramatic decrease in the ability of rhogdi to form a complex with rhoa, rac1, or cdc42.	SIGNOR-149282
P52333	O14939	1	phosphorylation	up-regulates	0.407	We identified three kinases capable of phosphorylating pld2 in vitro-epidermal growth factor receptor (egfr), jak3, and src (with jak3 reported for the first time in this study)-that phosphorylate an inhibitory, an activator, and an ambivalent (one that can yield either effect) site, respectively. Mass spectrometry analyses indicated the target of each of these kinases as y(296) for egfr, y(415) for jak3, and y(511) for src.	SIGNOR-163858
P62136	O95786	1	dephosphorylation	up-regulates activity	0.2	We identified PP1alpha and PP1gamma as primary phosphatases responsible for MDA5 and RIG-I dephosphorylation, leading to their activation.\|endogenous RIG-I and MDA5 that interacted with PP1 exhibited markedly decreased phosphorylation levels at S8 and S88, respectively	SIGNOR-264581
Q14653	Q14164	0	phosphorylation	up-regulates activity	0.741	Virus-induced phosphoactivation of irf-3, thought to be mediated directly or indirectly by ikk? And/or tbk1 occurs in the c-terminal region of irf-3 at seven ser/thr residues, 385sslentvdlhisnshplslts405 (fig. 1a).Within This region, irf-3 has two phosphorylation sites: site 1 includes ser385 and ser386, whereas site 2 includes ser396, ser398, ser402, ser405, and thr404.	SIGNOR-178379
P12931	P12830	1	phosphorylation	down-regulates quantity by destabilization	0.755	Activated c-Src phosphorylated E-cadherin at the tyrosine 797 site to initiate RNF43-mediated E-cadherin ubiquitination at lysine 816 and subsequent degradation	SIGNOR-274048
P19419	Q99102	1	transcriptional regulation	up-regulates quantity by expression	0.2	Through promoter screening, overexpressing methods and luciferase reporter studies, we found that transcription factors CREB, Ets-1, Elk-1 and STAT1 can positively regulate MUC4 expression at the promoter and mRNA level.	SIGNOR-254096
P46527	O43524	0	transcriptional regulation	up-regulates quantity	0.747	AFX transcriptionally activates p27kip1, resulting in increased protein levels.	SIGNOR-238610
P26038	Q9Y5S2	0	phosphorylation	up-regulates activity	0.2	In this study, we have shown that MRCKb phosphorylated moesin at Thr-558 \| We have shown that the phosphorylation is important to the formation of ®lopodia, and that MRCK may regulate this formation through the phosphorylation of ERM proteins at the tip of ®lopodia.	SIGNOR-260802
Q13315	Q96RU2	1	phosphorylation	up-regulates activity	0.311	These novel findings establish a direct connection between the ubiquitination of UCK1 by KLHL2 and phosphorylation of USP28 and UCK1 by ATM, which are involved in mediating drug resistance against 5'-AZA in AML patients.	SIGNOR-279007
P22681	O60674	1	ubiquitination	down-regulates quantity by destabilization	0.587	K63 linked poly-ubiquitination on K970 of JAK2 kinase domain is promoted by Cbl.	SIGNOR-278538
P25963	P18031	0	dephosphorylation	down-regulates	0.354	Ptp1b is able to dephosphorylate phosphorylated-tyr-42 on ikappabalpha	SIGNOR-45004
Q969Q1	P61088	0	ubiquitination	up-regulates activity	0.539	We used MuRF1 as the E3 as it functions with all these E2s to ubiquitinate one of its typical substrates, troponin I Although UbcH1 and UbcH13/Uev1a support ubiquitination of troponin I by MuRF1, these E2s do not support ubiquitination of S5a, unlike Class I E2s.	SIGNOR-272737
Q99638	P06493	0	phosphorylation	up-regulates activity	0.361	Here we present evidence that thr292 of hrad9 is subject to cdc2-dependent phosphorylation in mitosis. Furthermore, our data are also consistent with four other hrad9 phosphorylation sites (ser277, ser328, ser336, and thr355) being regulated in part by cdc2. We also identify ser387 as a novel site of hrad9 constitutive phosphorylation and show that phosphorylation at ser387 is a prerequisite for one form of dna damage-induced hyperphosphorylation of hrad9.	SIGNOR-101055
O95831	P04637	0	transcriptional regulation	up-regulates quantity by expression	0.351	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-267462
P67775	P04049	1	dephosphorylation	up-regulates	0.592	Both pp2a holoenzymes were found to associate with raf1 and catalyze dephosphorylation of inhibitory phospho-ser-259. Together these findings indicate that pp2a abalphac and abdeltac holoenzymes function as positive regulators of raf1-mek1/2-erk1/2 signaling by targeting raf1.	SIGNOR-141170
P07333	P16885	1	null	up-regulates	0.369	Studies with multipotent precursor cell lines (Fig. 4A) indicate that CSF-1R Tyr-807 and Tyr-721 promote macrophage differentiation via the PLC-Œ≥2 pathway	SIGNOR-255570
Q9NRD9	P17612	0	phosphorylation	up-regulates	0.2	We analyzed the duox1 phosphorylation state with an anti-rxx(ps/pt) antibody that could potentially recognize phosphorylation on ser955 and ser1217 but not on thr1007. duox1 but not duox2 activity is stimulated by forskolin (ec50 = 0.1 _m) via protein kinase a-mediated duox1 phosphorylation on serine 955. duox1 is positively regulated by the camp-dependent protein kinase a (pka)6 cascade	SIGNOR-183449
P49841	P20393	1	phosphorylation	up-regulates	0.282	We show here that gsk3beta phosphorylates and stabilizes the orphan nuclear receptor rev-erbalpha, a negative component of the circadian clock.	SIGNOR-144570
P05129	Q05586	1	phosphorylation	up-regulates activity	0.351	Serines 890 and 896 of the NMDA receptor subunit NR1 are differentially phosphorylated by protein kinase C isoforms. The results show that PKC alpha phosphorylates preferentially S896 and PKC gamma preferentially S890.	SIGNOR-263176
P30304	O14757	0	phosphorylation	down-regulates	0.857	The signal for ubiquitination after uv and ir exposure is created by phosphorylation of cdc25a mediated by chk1 and chk2, respectively. Chk1 is a major kinase phosphorylating cdc25a (ser76/124) and cdc25c (ser216).	SIGNOR-163134
Q13418	E9PAV3	1	phosphorylation	up-regulates	0.426	The inactivation of gsk3? In response to adhesion and ilk activation (6) would then result in a thr-159-hypophosphorylated ?-Nac that would become unavailable for proteasome degradation but would become a substrate for the ilk kinase activity on residue ser-43. The ser-43-phosphorylated ?-Nac would preferentially interact with c-jun (30), translocate to the nucleus, and potentiate transcription	SIGNOR-127631
Q9Y283	O14640	1	ubiquitination	down-regulates	0.641	Inversin inhibits the canonical wnt pathway by targeting cytoplasmic dishevelled (dsh or dvl1) for degradation	SIGNOR-135766
P49759	P18031	1	phosphorylation	up-regulates activity	0.347	The CLK family kinases, CLK1 and CLK2, phosphorylate and activate the tyrosine phosphatase, PTP-1B. \| although CLK1 and CLK2 directly phosphorylate PTP-1B on both Ser50 and Ser242/Ser243, the preferred CLK phosphorylation site is Ser50, as it is preferentially phosphorylated at an approximate ratio of 9:1 over the Ser242/Ser243 site.	SIGNOR-250773
O95714	P23025	1	ubiquitination	down-regulates	0.385	Herc2 may ubiquitinate xpa and thus target it for proteolytic degradation	SIGNOR-164595
P06850	P03372	0	transcriptional regulation	up-regulates quantity by expression	0.34	Evidence of direct estrogenic regulation of human corticotropin-releasing hormone gene expression. Potential implications for the sexual dimophism of the stress response and immune/inflammatory reaction.\|Gel retardation and immunoprecipitation demonstrated specific association between the perfect half-palindromic EREs of hCRH gene and the DNA binding domain of hER in vitro.	SIGNOR-268721
Q9Y6K1	P53350	0	phosphorylation	down-regulates activity	0.269	2.11 Plk1 Directly Phosphorylates DNMT3a at S393.\|Elevated Plk1 further inhibited DNMT3a via phosphorylation at S393 in mitosis in accord with its mitotic role during cell cycle.	SIGNOR-279552
P04150	P49715	1	transcriptional regulation	up-regulates quantity by expression	0.455	We show that in addition, DEX-bound GR directly promotes the expression of adipogenic TFs, including C/EBPβ, Klf5, Klf9, and C/EBPα	SIGNOR-256116
Q96E09	O14757	0	phosphorylation	down-regulates activity	0.2	Knockout of FAM122A results in activation of PP2A-B55α, a phosphatase that dephosphorylates the WEE1 protein and rescues WEE1 from ubiquitin-mediated degradation. in tumor cells with oncogene-driven replication stress, CHK1 can directly phosphorylate FAM122A, leading to activation of the PP2A-B55α phosphatase and increased WEE1 expression.	SIGNOR-266380
P48729	P17931	1	phosphorylation	up-regulates	0.308	These results indicate that phosphorylation of gal-3 promotes its nuclear export after apoptotic stimuli through enhanced nuclear export.	SIGNOR-124583
P31749	P21453	1	phosphorylation	up-regulates activity	0.704	Activated akt binds to edg-1 and phosphorylates the third intracellular loop at the t(236) residue. Transactivation of edg-1 by akt is not required for g(i)-dependent signaling but is indispensable for rac activation, cortical actin assembly, and chemotaxis	SIGNOR-252467
O95644	P52333	0	phosphorylation	up-regulates activity	0.383	Here we found that IL-7-Jak3 signals activated the transcription factor NFATc1 in DN thymocytes by phosphorylating Tyr371 in the regulatory region of NFATc1.	SIGNOR-276435
Q9UBK2	Q969H0	0	ubiquitination	down-regulates quantity by destabilization	0.398	We then examined the effect of necdin on ubiquitin-dependent degradation of PGC-1α using Rnf34, a PGC-1α E3 ubiquitin ligase22. Rnf34 reduced the PGC-1α level, and necdin completely inhibited the reduction (Fig. 4i). In addition, necdin strongly suppressed Rnf34-mediated ubiquitination of PGC-1α (Fig. 4j). Necdin also protected PGC-1α against ubiquitination mediated by Fbxw7, another PGC-1α E3 ubiquitin ligase23 (Fig. 4k). These data indicate that necdin stabilizes PGC-1α by inhibiting its degradation in the ubiquitin-proteasomal system.	SIGNOR-253394
P67870	P55010	1	phosphorylation	up-regulates activity	0.379	Mass spectrometric analysis of maximally in vitro phosphorylated eIF5 localized the major phosphorylation sites at Ser-387 and Ser-388 near the C-terminus of eIF5. These serine residues are embedded within a cluster of acidic amino acid residues and account for nearly 90% of the total in vitro eIF5 phosphorylation. A minor phosphorylation site at Ser-174 was also observed. \| The results suggest that phosphorylation of eIF5 may have a role in stimulating the rate of eIF5-promoted GTP hydrolysis.	SIGNOR-251070
P54829	Q12879	1	dephosphorylation	down-regulates activity	0.432	STEP inhibition by TC-2153 enhanced Tyr phosphorylation of GluN2A (XREF_FIG, 1 EGTA+TC-2153, n = 5, P < 0.05 compared with 1mM EGTA) without altering phosphorylation of Src (XREF_FIG, 1 EGTA+TC-2153, n = 5, P> 0.05 compared with 1 EGTA).\|These findings confirm that not only GluN2B and Fyn but also GluN2A are substrates of STEP.	SIGNOR-277089
Q8TBB1	P22459	1	ubiquitination	down-regulates quantity by destabilization	0.283	We used the Ligand of Numb protein X (LNX) family of E3s, a group of PDZ domain-containing RING-type E3 ubiquitin ligases, to demonstrate the feasibility of this strategy. Many potential substrates of LNX E3s were identified. Eight of the nine selected candidates were ubiquitinated in vitro, and two novel endogenous substrates, PDZ-binding kinase (PBK) and breakpoint cluster region protein (BCR), were confirmed in vivo.The C-terminal LNX1 PDZ1-binding motifs of the ATP-binding cassette, subfamily A member 1 (ABC-1), PBK, glutamate receptor, ionotropic, N-methyl d-aspartate 1 (GRIN1), and Claudin-17 significantly promoted the ubiquitination of the corresponding artificial degrons by LNX1ΔPDZ234.	SIGNOR-272899
Q12798	Q15154	0	relocalization	up-regulates	0.406	Rna silencing of pcm-1 leads to reduced assembly of centrin, pericentrin, and ninein at the centrosome	SIGNOR-94947
O14965	Q9Y6A5	1	phosphorylation	up-regulates activity	0.937	We show that this conserved serine on human TACC3 (Ser(558)) is also phosphorylated by Aurora A. Moreover, phosphorylation of TACC3 by Aurora A in human cells is essential for its proper localization to centrosomes and proximal mitotic spindles. Inhibition of Aurora A with the selective small molecule inhibitor MLN8054 in cultured human tumor cells resulted in mislocalization of TACC3 away from mitotic spindles in a concentration-dependent manner.	SIGNOR-262655
P05997	P13497	0	cleavage	up-regulates activity	0.607	BMP-1 Can Efficiently Cleave Pro-α1(V) N-propeptides and Pro-α2(V) C-propeptides and Less Efficiently Cleave Pro-α1(V) C-propeptides in Vitro. BMP-1 efficiently cleaves pro-α2(V) C-propeptides at a single site between residues 1250 (Glu) and 1251 (Asp).	SIGNOR-256343
P60953	Q6XZF7	0	guanine nucleotide exchange factor	up-regulates activity	0.572	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-260547

P49841

Q02750

0

phosphorylation

up-regulates activity

0.343

In vitro kinase assay was carried out using a recombinant human active mek1 and we found that gsk-3beta was phosphorylated on tyr(216) by this kinase in a dose- and time-dependent manner. Further, the pretreatment of fibroblasts with u0126 inhibited serum-induced nuclear translocation of gsk-3beta. These results suggested that mek1/2 induces tyrosine phosphorylation of gsk-3beta and this cellular event might induce nuclear translocation of gsk-3beta.

SIGNOR-236622

P51692

P18031

0

dephosphorylation

down-regulates activity

0.676

A Cytosolic Protein-tyrosine Phosphatase PTP1B Specifically Dephosphorylates and Deactivates Prolactin-activated STAT5a and STAT5b

SIGNOR-248429

P05231

O95644

0

transcriptional regulation

up-regulates quantity by expression

0.415

The calcineurin/nuclear factor of activated T cells (NFAT) signaling pathway has been found to play a role in regulating growth and differentiation in several cell types. However, the functional significance of NFAT in the vasculature is largely unclear. Here we show that NFATc1, NFATc3, and NFATc4 are expressed in human myometrial arteries. |Chronic inhibition of NFAT significantly reduced IL-6 production in intact myometrial arteries and inhibited cell proliferation in vascular smooth muscle cells cultured from explants from the same arteries.

SIGNOR-251730

Q9BXW9

Q13535

0

phosphorylation

up-regulates

0.673

In the present study, we identify two novel dna damage-inducible phosphorylation sites on fancd2, threonine 691 and serine 717. Atr phosphorylates fancd2 on these two sites, thereby promoting fancd2 monoubiquitination and enhancing cellular resistance to dna cross-linking agents

SIGNOR-149305

P07195

O14965

0

phosphorylation

up-regulates activity

0.2

Aurora-A-mediated phosphorylation of LDHB serine 162 significantly increases its activity in reducing pyruvate to lactate, which efficiently promotes NAD+ regeneration, glycolytic flux, lactate production and bio-synthesis with glycolytic intermediates.

SIGNOR-277493

Q92630

O14746

1

phosphorylation

down-regulates activity

0.444

Dyrk2 phosphorylates TERT protein, a catalytic subunit of telomerase.|In this study, we found that dual-specificity tyrosine-(Y)-phosphorylation-regulated kinase 2 (Dyrk2) negatively regulates telomerase activity.

SIGNOR-279611

Q9BTM1

Q86Y13

0

monoubiquitination

up-regulates activity

0.2

2A-HUB catalyzes monoubiquitination of H2A at lysine 119, functioning as a combinatoric component of the repression machinery required for specific gene regulation programs. Thus, 2A-HUB mediates a selective repression of a specific set of chemokine genes in macrophages, critically modulating migratory responses to TLR activation. H2A monoubiquitination acts to prevent FACT recruitment at the transcriptional promoter region, blocking RNA polymerase II release at the early stage of elongation.

SIGNOR-271763

O75582

P54253

1

phosphorylation

up-regulates quantity by stabilization

0.26

In summary, the data from the cell based screen, biochemical studies and genetic interactions strongly suggest that MSK1 phosphorylates ATXN1 and regulates its stability.

SIGNOR-279109

Q5SQI0

O43318

0

phosphorylation

up-regulates activity

0.2

Here we report TGF-beta-activated kinase 1 (TAK1) as a key activator of alphaTAT1. TAK1 directly interacts with and phosphorylates alphaTAT1 at Ser237 to critically enhance its catalytic activity

SIGNOR-272243

P24941

Q16584

1

phosphorylation

up-regulates activity

0.2

Using in vitro kinase assays and phosphomutants, we determined that CDK1 phosphorylates MLK3 on Ser548 and decreases MLK3 activity during mitosis, whereas CDK2 phosphorylates MLK3 on Ser770 and increases MLK3 activity during G1/S and G2 phases.

SIGNOR-277604

Q6IMN6

P01178

1

post transcriptional regulation

up-regulates quantity by stabilization

0.2

Transcriptional and post-transcriptional regulation of oxytocin and vasopressin gene expression by CREB3L1 and CAPRIN2|Altogether, the data indicate that CAPRIN2 binds Oxt mRNA |Therefore, we propose that CAPRIN2 facilitates post-transcriptional modifications that increase Oxt transcript stability.

SIGNOR-268556

P06493

Q06830

1

phosphorylation

down-regulates

0.35

Peroxiredoxin (prx) i is a member of the peroxiredoxin family of peroxidases and contains a consensus site (thr(90)-pro-lys-lys) for phosphorylation by cyclin-dependent kinases (cdks). This protein has now been shown to be phosphorylated specifically on thr(90) by several cdks, including cdc2, in vitro. Phosphorylation of prx i on thr(90) reduced the peroxidase activity of this protein by 80%.

SIGNOR-87097

Q8N752

P35222

1

phosphorylation

down-regulates

0.508

We show that a complex of axin and casein kinase i (cki) induces beta-catenin phosphorylation at a single site: serine 45 (s45).

SIGNOR-87430

O96017

Q9NY61

1

phosphorylation

up-regulates quantity by stabilization

0.358

Three putative Chk2 phosphorylation sites (Stevens et al., 2003) are present in Che-1 at resides Ser141, Ser474, and Ser508. Thus, we performed in vitro Chk2 kinase assays utilizing the GST-Che-1 fusion peptides spanning these residues as substrates.| Taken together, these results indicate that Chk2 phosphorylates Che-1 and this phosphorylation contributes to increase Che-1 stability.

SIGNOR-264416

P27361

O15525

1

phosphorylation

up-regulates quantity

0.368

By contrast, MAFG-S124A was not phosphorylated, indicating that ERK1 phosphorylates MAFG at S124.|Notably, cotransfection of ERK1 increased total levels of wild-type MAFG and MAFG-T3A but not MAFG-S124A, indicating that phosphorylation increased MAFG stability.

SIGNOR-280027

P24941

P03372

1

phosphorylation

up-regulates

0.477

The pi3k/akt pathway is necessary to activate cdk2, which phosphorylates eralphaser294, and mediates the binding between pin1 and eralpha

SIGNOR-200867

P51812

Q14790

1

phosphorylation

down-regulates quantity by destabilization

0.369

The ribosomal S6 kinase 2 (RSK2) is a member of the p90 ribosomal S6 kinase (p90RSK) family of proteins and plays a critical role in proliferation, cell cycle, and cell transformation. Here, we report that RSK2 phosphorylates caspase-8, and Thr-263 was identified as a novel caspase-8 phosphorylation site. In addition, we showed that EGF induces caspase-8 ubiquitination and degradation through the proteasome pathway, and phosphorylation of Thr-263 is associated with caspase-8 stability.

SIGNOR-272997

P10523

P46934

0

polyubiquitination

down-regulates quantity by destabilization

0.373

Here we report that NEDD4-1, a HECT domain-containing E3 ubiquitin ligase, binds via its HECT domain directly with SAG's C-terminal RING domain and ubiquitylates SAG for proteasome-mediated. We also found that SAG bridges NEDD4-1 via its C-terminus and CUL-5 via its N-terminus to form a NEDD4-1/SAG/CUL-5 tri-complex. Biologically, NEDD4-1 overexpression sensitizes cancer cells to etoposide-induced apoptosis by reducing SAG levels through targeted degradation. Thus, SAG is added to a growing list of NEDD4-1 substrates and mediates its biological function. degradation.

SIGNOR-272843

P08581

P23467

0

dephosphorylation

down-regulates

0.364

Ptp1b and shp-2 are bound to the c-met receptor to control its activity. Although the binding of ptp1b increases when there is a decrease in c-met activation and acts as a negative regulator of the receptor, the increased binding and phosphorylation of shp-2 coincide with maximal stimulation of c-met, acting as a positive regulator.

SIGNOR-139560

P50552

Q13976

0

phosphorylation

down-regulates activity

0.735

Vertebrate Ena/VASP proteins are phosphorylated by PKA, as well as PKG, and the phosphorylation is required for full function in a number of cellular contexts

SIGNOR-268289

P06493

Q13586

1

phosphorylation

down-regulates

0.345

Stim1 is phosphorylated during mitosis. Removal of ten mpm-2 recognition sites by truncation at amino acid 482 abolished mpm-2 recognition of mitotic stim1, and significantly rescued stim1 rearrangement and soce response in mitosis. We identified ser 486 and ser 668 as mitosis-specific phosphorylation sites, and stim1 containing mutations of these sites to alanine also significantly rescued mitotic soce.

SIGNOR-189017

Q04206

P60510

0

dephosphorylation

up-regulates activity

0.361

Suppression of MEK/ERK signaling pathway enhances cisplatin-induced NF-kappaB activation by protein phosphatase 4-mediated NF-kappaB p65 Thr dephosphorylation

SIGNOR-248549

P13224

P17612

0

phosphorylation

down-regulates activity

0.312

Platelet glycoprotein Ib beta is phosphorylated on serine 166 by cyclic AMP-dependent protein kinase. phosphorylation of this residue may contribute to the inhibitory actions of cyclic AMP by inhibiting collagen-induced polymerization of actin.

SIGNOR-249986

O14733

O43379

0

relocalization

up-regulates activity

0.294

In the WT brain, the WDR62 scaffold organizes a protein complex including MEKK3, MKK4/7, and JNK1 to control NPC development during corticogenesis

SIGNOR-271716

P07101

P51812

0

phosphorylation

up-regulates

0.267

Mitogen-activated protein-kinase (map) kinase-activated protein kinases 1 and 2 (mapkap kinase-1, mapkap kinase-2), were found to phosphorylate bacterially expressed human tyrosine hydroxylaserecombinant human tyrosine hydroxylase (hth1) was found to be phosphorylated by mitogen and stress-activated protein kinase 1 (msk1) at ser40 and by p38 regulated/activated kinase (prak) on ser19. Phosphorylation by msk1 induced an increase in vmax

SIGNOR-34682

P55211

Q13627

0

phosphorylation

down-regulates activity

0.388

Depletion of DYRK1A from human cells by short interfering RNA inhibits the basal phosphorylation of caspase 9 at an inhibitory site, Thr125. DYRK1A-dependent phosphorylation of Thr125 is also blocked by harmine, confirming the use of this beta-carboline alkaloid as a potent inhibitor of DYRK1A in cells.|When co-expressed in cells, DYRK1A interacts with caspase 9, strongly induces Thr125 phosphorylation and inhibits caspase 9 auto-processing.

SIGNOR-279326

P31749

P99999

1

phosphorylation

down-regulates activity

0.465

Finally, we propose that pro-survival kinase Akt (protein kinase B) is a likely mediator of the S47 phosphorylation of Cytc in the brain.

SIGNOR-277237

P31749

Q16763

1

phosphorylation

up-regulates quantity by stabilization

0.437

Mechanistically, Akt1 physically interacted with and phosphorylated UBE2S at Thr 152, enhancing its stability by inhibiting proteasomal degradation.

SIGNOR-265078

P25098

O76070

1

phosphorylation

down-regulates activity

0.2

GRK-mediated phosphorylation inhibits synuclein's interaction with both phospholipids and PLD2. Mutation of Ser124 dramatically inhibits γ-synuclein phosphorylation by GRK2

SIGNOR-251204

Q14674

P53350

0

phosphorylation

down-regulates activity

0.772

Although mutation of serine 1126 and threonine 1346 to alanine had no effect (lanes 2 and 5), additional mutation of threonine 1363 and serine 1399 rendered separase almost completely resistant to phosphorylation (lane 3). Serine 1399 seems to be the one residue within this large separase fragment that is most efficiently phosphorylated by polo-like kinase, because a corresponding point mutation was sufficient to reduce the labeling by 80% compared with wild type (lane 6).

SIGNOR-276082

Q15797

Q04771

0

phosphorylation

up-regulates activity

0.703

ALK2 receptor specifically interacts with and phosphorylates Smad1 protein. ALK2 Activates Smad1 and Induces BMP-specific Signals. Biochemical analysis revealed that constitutively active ALK2 associated with and phosphorylated Smad1 on the COOH-terminal SSXS motif

SIGNOR-251439

Q92995

P11441

1

deubiquitination

up-regulates activity

0.61

USP13 and gp78 control ubiquitination of Ubl4A.These data suggest that USP13 and gp78 play antagonizing roles in regulation of Ubl4A ubiquitination: While gp78 assembles ubiquitin chains on Ubl4A, USP13 antagonizes this activity to limit Ubl4A ubiquitination.Ubiquitination of Ubl4A preferentially occurs on Lys48. We identify the Bag6 cofactor Ubl4A as a shared substrate of gp78 and USP13. USP13 depletion is associated with hyper-ubiquitination of Ubl4A and altered interaction between the Bag6 complex and its co-chaperone SGTA. Because the interaction of Ubl4A with SGTA is mediated by positively-charged residues in Ubl4A including Lys48 (Chartron et al., 2012; Xu et al., 2012), which happens to be the major ubiquitination site, the simplest model to explain reduced Bag6-SGTA interaction in USP13 knockdown cells is that ubiquitin conjugates on Ubl4A sterically hinder SGTA binding.

SIGNOR-272857

P45983

Q96P20

1

phosphorylation

up-regulates activity

0.369

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

SIGNOR-280034

O15169

Q9H2K2

0

ADP-ribosylation

down-regulates quantity by destabilization

0.705

Together, these findings are consistent with the hypothesis that TNKS promotes the ubiquitination and degradation of axin, which may be mediated, at least in part, through the direct PARsylation of axin.

SIGNOR-263378

Q12933

Q8IUC6

1

polyubiquitination

up-regulates

0.433

Here, we show that the TRAF family proteins directly bind TICAM-1 and demonstrate that TRAF2 and TRAF6 bind different sites of the N-terminal TICAM-1 and accelerate its polyubiquitination. we speculate that polyubiquitination of TICAM-1 by TRAF2 and TRAF6 is required for TICAM-1 to induce IRF-3 and NF-κB activation. This is supported by the observation that polyubiquitination of TICAM-1 was required for TRAF3-binding to TICAM-1

SIGNOR-271427

P09211

P05129

0

phosphorylation

up-regulates activity

0.2

Peptide phosphorylation analyses and both phosphorylation and enzyme kinetic studies with GSTP1 proteins mutated at candidate amino acid residues established Ser-42 and Ser-184 as putative phospho-acceptor residues for both kinases in the GSTP1 protein. Together, these findings show PKA- and PKC-dependent phosphorylation as a significant post-translational mechanism of regulation of GSTP1 function. Together, these results further support S42 and S184 as major phosphor-acceptor residues for PKA and PKC and suggest that the increased activity of the phospho-GSTP1 was not simply a consequence of the negative charge introduced in the GSTP1 protein by the phosphate group.All eight PKC isoforms, PKC-α, PKC-βI, PKC-βII, PKC-ε, PKC-γ, PKC-η, and PKC-ζ phosphorylated the GSTP1 protein efficiently

SIGNOR-276018

P35558

Q86UZ6

0

transcriptional regulation

up-regulates quantity by expression

0.2

We identified LIF/ZBTB46 signalling as a key promoter of metabolic reprogramming and NE differentiation of PCa cells through interactions with PCK1. We showed that ZBTB46 directly upregulates the expression of PCK1 and NE marker gene through activation of LIF signalling.

SIGNOR-277987

Q9NS56

P04637

1

ubiquitination

down-regulates

0.461

Plk1-mediated phosphorylation of topors regulates p53 stabilityherein, we have identified topoisomerase i-binding protein (topors), a p53-binding protein, as a plk1 target. We show that plk1 phosphorylates topors on ser(718) in vivo. Significantly, expression of a plk1-unphosphorylatable topors mutant (s718a) leads to a dramatic accumulation of p53 through inhibition of p53 degradation. Topors is an ubiquitin and small ubiquitin-like modifier ubiquitin-protein isopeptide ligase (sumo e3) ligase. Plk1-mediated phosphorylation of topors inhibits topors-mediated sumoylation of p53, whereas p53 ubiquitination is enhanced, leading to p53 degradation.

SIGNOR-185848

P24941

Q07817

1

phosphorylation

up-regulates activity

0.496

Our findings show that Cdk2 phosphorylation of Bcl-xL at Ser73, but not the Bcl-xL cleavage products, is necessary and sufficient to induce cell death.

SIGNOR-278242

P63151

P30291

1

dephosphorylation

up-regulates quantity by stabilization

0.385

Knockout of FAM122A results in activation of PP2A-B55α, a phosphatase that dephosphorylates the WEE1 protein and rescues WEE1 from ubiquitin-mediated degradation. in tumor cells with oncogene-driven replication stress, CHK1 can directly phosphorylate FAM122A, leading to activation of the PP2A-B55α phosphatase and increased WEE1 expression.

SIGNOR-266381

P42574

P55212

1

cleavage

up-regulates

0.619

Caspase-3 is required for the activation of caspases 6

SIGNOR-64179

P28482

Q9BUB5

1

phosphorylation

up-regulates

0.594

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 toward a substrate, eukaryotic initiation factor-4e (eif-4e).

SIGNOR-48298

Q9UI95

Q92733

0

relocalization

up-regulates

0.496

We found that the human papillary renal cell carcinoma-associated proteinprccinteracts with the cell cycle control proteinmad2b, and translocates this protein to the nucleus where it exerts its mitotic checkpoint function.

SIGNOR-126516

P37231

P17676

0

transcriptional regulation

up-regulates quantity

0.729

Induction of C/EBP beta DNA-binding activity in NIH-3T3 beta 2 cells exposed to dexamethasone in the presence of insulin and fetal bovine serum activates the expression of an adipocyte-specific nuclear hormone receptor, PPAR gamma, that stimulates the conversion of these fibroblasts into committed preadipocytes

SIGNOR-255730

P55317

P10275

1

transcriptional regulation

down-regulates quantity by repression

0.766

FOXA1 directly inhibits AR expression and thus the transcription of its target genes. FOXA1 inhibits AR gene expression in prostate cancer. oss of FOXA1 may lead to androgen-independent AR signaling and thus castration-resistant prostate cancer progression. Indeed, we have recently reported that FOXA1 is downregulated in CRPC

SIGNOR-251541

O14641

P60484

0

dephosphorylation

down-regulates activity

0.318

This showed that while both PTEN WT and the lipid phosphatase-inactive G129E mutant suppressed phosphorylation of DVL2 on serine 143 that accumulated upon PTEN knockdown, the C124S and Y138L mutants did not .|Finally, it is important to point out that while our studies show that PTEN can directly dephosphorylate DVL2 in vitro, it is possible that regulation of serine 143 phosphorylation of DVL2 by PTEN in cells may require additional protein factors, or post-translational modifications.

SIGNOR-277035

Q86YJ5

P15151

1

ubiquitination

down-regulates quantity by destabilization

0.2

MARCH9, a member of the RING-CH family of transmembrane E3 ubiquitin ligases, down-regulates CD4, major histocompatibility complex-I (MHC), and ICAM-1 in lymphoid cells. To identify novel MARCH9 substrates, we used high throughput flow cytometry and quantitative mass spectrometry by stable isotope labeling by amino acids in cell culture (SILAC) to determine the differential expression of plasma membrane proteins in a MARCH9-expressing B cell line. This combined approach identified 13 potential new MARCH9 targets.

SIGNOR-271530

Q9UI32

P23771

0

transcriptional regulation

up-regulates quantity by expression

0.332

Thus, GATA3 contributes to the elevated expression of GLS2 in luminal-subtype breast cancers.

SIGNOR-268034

O14920

Q99759

0

phosphorylation

up-regulates activity

0.569

Genetic analysis showed that MEKK3, which is thought to activate IKK2 through phosphorylation (Yang et al., 2001), is necessary for TNF-alpha-induced NF-kappaB activation.|Our results also suggest that IKK2 is phosphorylated on S177 and S181 on its activation loop by MEKK3.

SIGNOR-279468

Q06187

P16885

1

phosphorylation

up-regulates

0.778

By measuring the ability of human plcgamma2 to restore calcium responses to the b-cell receptor stimulation or oxidative stress in a b-cell line (dt40) deficient in plcgamma2, we have demonstrated that two tyrosine residues, tyr(753) and tyr(759), were important for the plcgamma2 signaling function.Of the two kinases that previously have been proposed to phosphorylate plcgamma2, btk, and syk, purified btk had much greater ability to phosphorylate recombinant plcgamma2 in vitro, whereas syk efficiently phosphorylated adapter protein blnk.

SIGNOR-111069

O43379

O14733

1

relocalization

up-regulates activity

0.294

In the WT brain, the WDR62 scaffold organizes a protein complex including MEKK3, MKK4/7, and JNK1 to control NPC development during corticogenesis

SIGNOR-271716

O00409

Q9P1W9

1

transcriptional regulation

down-regulates quantity by repression

0.297

CHES1/FOXN3 regulates cell proliferation by repressing PIM2 and protein biosynthesis.

SIGNOR-261607

P35240

Q13153

0

phosphorylation

down-regulates

0.645

Merlin contains a c-terminal serine 518, which is phosphorylated both by p21-activated kinase (pak) and protein kinase a (pka) (shaw et al., 2001;kissil et al., 2002;xiao et al., 2002;alfthan et al., 2004). Phosphorylation at this site is predicted to result in a more open conformation incapable of inhibiting cell growth,

SIGNOR-159764

P19174

O60260

0

ubiquitination

down-regulates quantity

0.2

In order to address the functional role of parkin ubiquitination of PLCgamma1, we investigated PLC activity in human neuroblastoma SH-SY5Y cell lines stably transfected with either WT, or mutant R42P or G328E parkin.|WT parkin expression significantly reduced the levels of PLCgamma1 in human neuroblastoma.

SIGNOR-278592

Q8N653

P01116

1

ubiquitination

down-regulates activity

0.25

By trapping LZTR1 complexes from intact mammalian cells, we identified the guanosine triphosphatase RAS as a substrate for the LZTR1-CUL3 complex. Ubiquitome analysis showed that loss of Lztr1 abrogated Ras ubiquitination at lysine-170. LZTR1-mediated ubiquitination inhibited RAS signaling by attenuating its association with the membrane.

SIGNOR-269068

P68400

P35579

1

phosphorylation

up-regulates

0.34

In egf-stimulated cells, the myosin-iia heavy chain is phosphorylated on the casein kinase 2 site (s1943)

SIGNOR-155987

Q9NYL2

P52566

1

phosphorylation

down-regulates activity

0.2

In the present study, we provide evidence that ZAK serves as a RhoGDIbeta kinase, and demonstrate the phosphorylation of RhoGDIbeta by ZAK in vitro, as well as the physical association between ZAK and RhoGDIbeta.|These two proteins could negatively regulate one another such that ZAK suppresses RhoGDIbeta functions through phosphorylation and RhoGDIbeta counteracts the effects of ZAK by physical interaction.

SIGNOR-279633

P07954

P78527

0

phosphorylation

up-regulates activity

0.2

We show that exposure to ionizing radiation induces DNA-PK-dependent phosphorylation of nuclear fumarase at Thr 236, which leads to an interaction between fumarase and the histone variant H2A.Z at DNA double-strand break (DSB) regions.

SIGNOR-266349

P08253

Q9NPA2

0

cleavage

up-regulates activity

0.375

Direct activation of pro-matrix metalloproteinase-2 by leukolysin/membrane-type 6 matrix metalloproteinase/matrix metalloproteinase 25 at the asn(109)-Tyr bond. Leukolysin Cleaves ProMMP-2 at Asn66-Leu and Asn109-Tyr.

SIGNOR-256345

P31751

Q01860

1

phosphorylation

up-regulates quantity by stabilization

0.255

Here we show that in ECCs, Akt phosphorylated the master pluripotency factor Oct4 at threonine 235, and that the levels of phosphorylated Oct4 in ECCs correlated with resistance to apoptosis and tumorigenic potential. Phosphorylation of Oct4 increased its stability and facilitated its nuclear localization and its interaction with Sox2, which promoted the transcription of the core stemness genes POU5F1 and NANOG.

SIGNOR-242097

P19838

Q96FX8

0

ubiquitination

down-regulates quantity

0.2

We identify KPC1 as the Ub ligase (E3) that binds to the ankyrin repeats domain of p105, ubiquitinates it, and mediates its processing both under basal conditions and following signaling

SIGNOR-255843

P12931

P52565

1

phosphorylation

down-regulates

0.399

We show here that src kinase binds and phosphorylates rhogdi both in vitro and in vivo at tyr156. analysis of rho gtpase-rhogdi complexes using in vitro assays of complexation and in vivo by coimmunoprecipitation analysis indicates that src-mediated phosphorylation of tyr156 causes a dramatic decrease in the ability of rhogdi to form a complex with rhoa, rac1, or cdc42.

SIGNOR-149282

P52333

O14939

1

phosphorylation

up-regulates

0.407

We identified three kinases capable of phosphorylating pld2 in vitro-epidermal growth factor receptor (egfr), jak3, and src (with jak3 reported for the first time in this study)-that phosphorylate an inhibitory, an activator, and an ambivalent (one that can yield either effect) site, respectively. Mass spectrometry analyses indicated the target of each of these kinases as y(296) for egfr, y(415) for jak3, and y(511) for src.

SIGNOR-163858

P62136

O95786

1

dephosphorylation

up-regulates activity

0.2

We identified PP1alpha and PP1gamma as primary phosphatases responsible for MDA5 and RIG-I dephosphorylation, leading to their activation.|endogenous RIG-I and MDA5 that interacted with PP1 exhibited markedly decreased phosphorylation levels at S8 and S88, respectively

SIGNOR-264581

Q14653

Q14164

0

phosphorylation

up-regulates activity

0.741

Virus-induced phosphoactivation of irf-3, thought to be mediated directly or indirectly by ikk? And/or tbk1 occurs in the c-terminal region of irf-3 at seven ser/thr residues, 385sslentvdlhisnshplslts405 (fig. 1a).Within This region, irf-3 has two phosphorylation sites: site 1 includes ser385 and ser386, whereas site 2 includes ser396, ser398, ser402, ser405, and thr404.

SIGNOR-178379

P12931

P12830

1

phosphorylation

down-regulates quantity by destabilization

0.755

Activated c-Src phosphorylated E-cadherin at the tyrosine 797 site to initiate RNF43-mediated E-cadherin ubiquitination at lysine 816 and subsequent degradation

SIGNOR-274048

P19419

Q99102

1

transcriptional regulation

up-regulates quantity by expression

0.2

Through promoter screening, overexpressing methods and luciferase reporter studies, we found that transcription factors CREB, Ets-1, Elk-1 and STAT1 can positively regulate MUC4 expression at the promoter and mRNA level.

SIGNOR-254096

P46527

O43524

0

transcriptional regulation

up-regulates quantity

0.747

AFX transcriptionally activates p27kip1, resulting in increased protein levels.

SIGNOR-238610

P26038

Q9Y5S2

0

phosphorylation

up-regulates activity

0.2

In this study, we have shown that MRCKb phosphorylated moesin at Thr-558 | We have shown that the phosphorylation is important to the formation of ®lopodia, and that MRCK may regulate this formation through the phosphorylation of ERM proteins at the tip of ®lopodia.

SIGNOR-260802

Q13315

Q96RU2

1

phosphorylation

up-regulates activity

0.311

These novel findings establish a direct connection between the ubiquitination of UCK1 by KLHL2 and phosphorylation of USP28 and UCK1 by ATM, which are involved in mediating drug resistance against 5'-AZA in AML patients.

SIGNOR-279007

P22681

O60674

1

ubiquitination

down-regulates quantity by destabilization

0.587

K63 linked poly-ubiquitination on K970 of JAK2 kinase domain is promoted by Cbl.

SIGNOR-278538

P25963

P18031

0

dephosphorylation

down-regulates

0.354

Ptp1b is able to dephosphorylate phosphorylated-tyr-42 on ikappabalpha

SIGNOR-45004

Q969Q1

P61088

0

ubiquitination

up-regulates activity

0.539

We used MuRF1 as the E3 as it functions with all these E2s to ubiquitinate one of its typical substrates, troponin I Although UbcH1 and UbcH13/Uev1a support ubiquitination of troponin I by MuRF1, these E2s do not support ubiquitination of S5a, unlike Class I E2s.

SIGNOR-272737

Q99638

P06493

0

phosphorylation

up-regulates activity

0.361

Here we present evidence that thr292 of hrad9 is subject to cdc2-dependent phosphorylation in mitosis. Furthermore, our data are also consistent with four other hrad9 phosphorylation sites (ser277, ser328, ser336, and thr355) being regulated in part by cdc2. We also identify ser387 as a novel site of hrad9 constitutive phosphorylation and show that phosphorylation at ser387 is a prerequisite for one form of dna damage-induced hyperphosphorylation of hrad9.

SIGNOR-101055

O95831

P04637

0

transcriptional regulation

up-regulates quantity by expression

0.351

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-267462

P67775

P04049

1

dephosphorylation

up-regulates

0.592

Both pp2a holoenzymes were found to associate with raf1 and catalyze dephosphorylation of inhibitory phospho-ser-259. Together these findings indicate that pp2a abalphac and abdeltac holoenzymes function as positive regulators of raf1-mek1/2-erk1/2 signaling by targeting raf1.

SIGNOR-141170

P07333

P16885

1

null

up-regulates

0.369

Studies with multipotent precursor cell lines (Fig. 4A) indicate that CSF-1R Tyr-807 and Tyr-721 promote macrophage differentiation via the PLC-Œ≥2 pathway

SIGNOR-255570

Q9NRD9

P17612

0

phosphorylation

up-regulates

0.2

We analyzed the duox1 phosphorylation state with an anti-rxx(ps/pt) antibody that could potentially recognize phosphorylation on ser955 and ser1217 but not on thr1007. duox1 but not duox2 activity is stimulated by forskolin (ec50 = 0.1 _m) via protein kinase a-mediated duox1 phosphorylation on serine 955. duox1 is positively regulated by the camp-dependent protein kinase a (pka)6 cascade

SIGNOR-183449

P49841

P20393

1

phosphorylation

up-regulates

0.282

We show here that gsk3beta phosphorylates and stabilizes the orphan nuclear receptor rev-erbalpha, a negative component of the circadian clock.

SIGNOR-144570

P05129

Q05586

1

phosphorylation

up-regulates activity

0.351

Serines 890 and 896 of the NMDA receptor subunit NR1 are differentially phosphorylated by protein kinase C isoforms. The results show that PKC alpha phosphorylates preferentially S896 and PKC gamma preferentially S890.

SIGNOR-263176

P30304

O14757

0

phosphorylation

down-regulates

0.857

The signal for ubiquitination after uv and ir exposure is created by phosphorylation of cdc25a mediated by chk1 and chk2, respectively. Chk1 is a major kinase phosphorylating cdc25a (ser76/124) and cdc25c (ser216).

SIGNOR-163134

Q13418

E9PAV3

1

phosphorylation

up-regulates

0.426

The inactivation of gsk3? In response to adhesion and ilk activation (6) would then result in a thr-159-hypophosphorylated ?-Nac that would become unavailable for proteasome degradation but would become a substrate for the ilk kinase activity on residue ser-43. The ser-43-phosphorylated ?-Nac would preferentially interact with c-jun (30), translocate to the nucleus, and potentiate transcription

SIGNOR-127631

Q9Y283

O14640

1

ubiquitination

down-regulates

0.641

Inversin inhibits the canonical wnt pathway by targeting cytoplasmic dishevelled (dsh or dvl1) for degradation

SIGNOR-135766

P49759

P18031

1

phosphorylation

up-regulates activity

0.347

The CLK family kinases, CLK1 and CLK2, phosphorylate and activate the tyrosine phosphatase, PTP-1B. | although CLK1 and CLK2 directly phosphorylate PTP-1B on both Ser50 and Ser242/Ser243, the preferred CLK phosphorylation site is Ser50, as it is preferentially phosphorylated at an approximate ratio of 9:1 over the Ser242/Ser243 site.

SIGNOR-250773

O95714

P23025

1

ubiquitination

down-regulates

0.385

Herc2 may ubiquitinate xpa and thus target it for proteolytic degradation

SIGNOR-164595

P06850

P03372

0

transcriptional regulation

up-regulates quantity by expression

0.34

Evidence of direct estrogenic regulation of human corticotropin-releasing hormone gene expression. Potential implications for the sexual dimophism of the stress response and immune/inflammatory reaction.|Gel retardation and immunoprecipitation demonstrated specific association between the perfect half-palindromic EREs of hCRH gene and the DNA binding domain of hER in vitro.

SIGNOR-268721

Q9Y6K1

P53350

0

phosphorylation

down-regulates activity

0.269

2.11 Plk1 Directly Phosphorylates DNMT3a at S393.|Elevated Plk1 further inhibited DNMT3a via phosphorylation at S393 in mitosis in accord with its mitotic role during cell cycle.

SIGNOR-279552

P04150

P49715

1

transcriptional regulation

up-regulates quantity by expression

0.455

We show that in addition, DEX-bound GR directly promotes the expression of adipogenic TFs, including C/EBPβ, Klf5, Klf9, and C/EBPα

SIGNOR-256116

Q96E09

O14757

0

phosphorylation

down-regulates activity

0.2

Knockout of FAM122A results in activation of PP2A-B55α, a phosphatase that dephosphorylates the WEE1 protein and rescues WEE1 from ubiquitin-mediated degradation. in tumor cells with oncogene-driven replication stress, CHK1 can directly phosphorylate FAM122A, leading to activation of the PP2A-B55α phosphatase and increased WEE1 expression.

SIGNOR-266380

P48729

P17931

1

phosphorylation

up-regulates

0.308

These results indicate that phosphorylation of gal-3 promotes its nuclear export after apoptotic stimuli through enhanced nuclear export.

SIGNOR-124583

P31749

P21453

1

phosphorylation

up-regulates activity

0.704

Activated akt binds to edg-1 and phosphorylates the third intracellular loop at the t(236) residue. Transactivation of edg-1 by akt is not required for g(i)-dependent signaling but is indispensable for rac activation, cortical actin assembly, and chemotaxis

SIGNOR-252467

O95644

P52333

0

phosphorylation

up-regulates activity

0.383

Here we found that IL-7-Jak3 signals activated the transcription factor NFATc1 in DN thymocytes by phosphorylating Tyr371 in the regulatory region of NFATc1.

SIGNOR-276435

Q9UBK2

Q969H0

0

ubiquitination

down-regulates quantity by destabilization

0.398

We then examined the effect of necdin on ubiquitin-dependent degradation of PGC-1α using Rnf34, a PGC-1α E3 ubiquitin ligase22. Rnf34 reduced the PGC-1α level, and necdin completely inhibited the reduction (Fig. 4i). In addition, necdin strongly suppressed Rnf34-mediated ubiquitination of PGC-1α (Fig. 4j). Necdin also protected PGC-1α against ubiquitination mediated by Fbxw7, another PGC-1α E3 ubiquitin ligase23 (Fig. 4k). These data indicate that necdin stabilizes PGC-1α by inhibiting its degradation in the ubiquitin-proteasomal system.

SIGNOR-253394

P67870

P55010

1

phosphorylation

up-regulates activity

0.379

Mass spectrometric analysis of maximally in vitro phosphorylated eIF5 localized the major phosphorylation sites at Ser-387 and Ser-388 near the C-terminus of eIF5. These serine residues are embedded within a cluster of acidic amino acid residues and account for nearly 90% of the total in vitro eIF5 phosphorylation. A minor phosphorylation site at Ser-174 was also observed. | The results suggest that phosphorylation of eIF5 may have a role in stimulating the rate of eIF5-promoted GTP hydrolysis.

SIGNOR-251070

P54829

Q12879

1

dephosphorylation

down-regulates activity

0.432

STEP inhibition by TC-2153 enhanced Tyr phosphorylation of GluN2A (XREF_FIG, 1 EGTA+TC-2153, n = 5, P < 0.05 compared with 1mM EGTA) without altering phosphorylation of Src (XREF_FIG, 1 EGTA+TC-2153, n = 5, P> 0.05 compared with 1 EGTA).|These findings confirm that not only GluN2B and Fyn but also GluN2A are substrates of STEP.

SIGNOR-277089

Q8TBB1

P22459

1

ubiquitination

down-regulates quantity by destabilization

0.283

We used the Ligand of Numb protein X (LNX) family of E3s, a group of PDZ domain-containing RING-type E3 ubiquitin ligases, to demonstrate the feasibility of this strategy. Many potential substrates of LNX E3s were identified. Eight of the nine selected candidates were ubiquitinated in vitro, and two novel endogenous substrates, PDZ-binding kinase (PBK) and breakpoint cluster region protein (BCR), were confirmed in vivo.The C-terminal LNX1 PDZ1-binding motifs of the ATP-binding cassette, subfamily A member 1 (ABC-1), PBK, glutamate receptor, ionotropic, N-methyl d-aspartate 1 (GRIN1), and Claudin-17 significantly promoted the ubiquitination of the corresponding artificial degrons by LNX1ΔPDZ234.

SIGNOR-272899

Q12798

Q15154

0

relocalization

up-regulates

0.406

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

SIGNOR-94947

O14965

Q9Y6A5

1

phosphorylation

up-regulates activity

0.937

We show that this conserved serine on human TACC3 (Ser(558)) is also phosphorylated by Aurora A. Moreover, phosphorylation of TACC3 by Aurora A in human cells is essential for its proper localization to centrosomes and proximal mitotic spindles. Inhibition of Aurora A with the selective small molecule inhibitor MLN8054 in cultured human tumor cells resulted in mislocalization of TACC3 away from mitotic spindles in a concentration-dependent manner.

SIGNOR-262655

P05997

P13497

0

cleavage

up-regulates activity

0.607

BMP-1 Can Efficiently Cleave Pro-α1(V) N-propeptides and Pro-α2(V) C-propeptides and Less Efficiently Cleave Pro-α1(V) C-propeptides in Vitro. BMP-1 efficiently cleaves pro-α2(V) C-propeptides at a single site between residues 1250 (Glu) and 1251 (Asp).

SIGNOR-256343

P60953

Q6XZF7

0

guanine nucleotide exchange factor

up-regulates activity

0.572

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-260547