GleghornLab/Signor_2class · Datasets at Hugging Face

IdA string	IdB string	labels int64	mechanism string	effect string	score float64	sentence string	signor_id string
Q32MZ4	P43405	0	phosphorylation	up-regulates activity	0.2	However, this inhibitory activity TRIP can be reversed by the co-expression of Syk, which might inhibit the activity of cytoplasmic TRIP, sequester TRIP from important nucleolar targets or even counter TRIP 's inhibitory effects on TRAF and TNF signaling by regulating the activity of alternative components of the pathway.\|Syk induces phosphorylation of TRIP on tyrosine.	SIGNOR-279297
P28482	P24723	0	phosphorylation	up-regulates activity	0.506	Protein kinase C-eta regulates Mcl-1 level via ERK1. knockdown of PKCη but not PKCα, -δ or -ε caused a significant decrease in ERK (extracellular signal-regulated kinase) phosphorylation. Knockdown of ERK1 but not ERK2 decreased Mcl-1 level, and the decrease in Mcl-1 caused by PKCη knockdown was restored by ERK1 overexpression. These results suggest that PKCη utilizes the ERK signaling pathway to protect against ubiquitin-mediated proteasomal degradation of Mcl-1.	SIGNOR-261910
Q04206	P11309	0	phosphorylation	up-regulates	0.2	In this study we show that phosphorylation of rela/p65 at ser276 prevents its degradation by ubiquitin-mediated proteolysis. importantly, we identify pim-1 as a further kinase responsible for the phosphorylation of rela/p65 at ser276.	SIGNOR-189125
Q13480	P27361	0	phosphorylation	up-regulates activity	0.633	Our results demonstrate that ERK1/2 phosphorylate Gab1 at six serine/threonine residues (T312, S381, S454, T476, S581, S597) in consensus motifs for MAP kinase phosphorylation. \|serine and threonine phosphorylation are capable of modulating the initial signal	SIGNOR-249464
Q63HK5	Q13547	1	relocalization	up-regulates activity	0.2	We carried out yeast two-hybrid studies with a PTB domain of FE65, focusing on those genes that might be involved in nuclear signaling, and identified and validated Teashirt proteins as FE65 interacting proteins in neurons. Using reporter systems, we observed that FE65 could simultaneously recruit SET, a component of the inhibitor of acetyl transferase, and Teashirt, which in turn recruited histone deacetylases, to produce a powerful gene-silencing complex.Endogenous HDAC1 was co-immunoprecipitated with FE65 when both FE65 and Teashirt3 were co-transfected (lane 4), but not when Teashirt3 or FE65 was omitted (lane 5 and 6), confirming that the association of HDAC1 with FE65 is dependent on, and mediated, by Teashirt3.	SIGNOR-264814
P46937	Q4VCS5	0	relocalization	down-regulates	0.734	Yap/taz and angiomotin (amot) family proteins were shown to interact, resulting in yap/taz localization to tight junctions and inhibition through phosphorylation-dependent and -independent mechanisms.	SIGNOR-175779
P30305	P53350	0	phosphorylation	up-regulates activity	0.663	These data indicated that PLK1 phosphorylates CDC25B and that pre-phosphorylation of CDC25B by CDK1/CyclinB enhances its substrate properties for PLK1 in vitro	SIGNOR-267560
P24941	Q99728	1	phosphorylation	down-regulates activity	0.609	CDK2-cyclin A1/E1 and CDK1-cyclin B1 phosphorylate BARD1 on its NH(2) terminus in vivo and in vitro. 44999999="E1" 45999998="terminus"}\|Here we show that the ubiquitin ligase activity of BRCA1-BARD1 is down-regulated by CDK2.	SIGNOR-280211
Q05655	Q16658	1	phosphorylation	down-regulates activity	0.324	Phosphorylation of human fascin inhibits its actin binding and bundling activities.	SIGNOR-248944
Q9Y5A7	Q00987	0	ubiquitination	up-regulates activity	0.276	Our results rather suggest that Mdm2 specifically ubiquitinates NUB1 on lysine 159 and that this modification is required for NUB1 functions.\|We conclude that Mdm2 acts as a positive regulator of NUB1 function, by modulating NUB1 ubiquitination on lysine 159.	SIGNOR-278556
P17275	P49841	0	phosphorylation	down-regulates quantity by destabilization	0.2	Thus, JunB phosphorylation at S251 and T255 by GSK3β is primed by phosphorylation at S259 by a yet to-be-identified kinase.Phosphorylation at S251, T255 and S259 is required for JunB degradation.	SIGNOR-276417
Q9UDY8	Q5T447	0	polyubiquitination	up-regulates quantity by stabilization	0.366	HECTD3 promotes MALT1 ubiquitination with nondegradative polyubiquitin chains by direct interacting with the MALT1 through its N-terminal destruction of cyclin domain. HECTD3 does not target MALT1 for degradation but stabilize it.	SIGNOR-272096
Q9HCE7	Q13243	1	ubiquitination	down-regulates quantity by destabilization	0.262	K125 was also the major site of SRSF5 ubiquitylation mediated by Smurf1.\|Smurf1 targets SRSF5 for degradation upon low glucose	SIGNOR-278665
Q13547	Q01543	1	deacetylation	up-regulates	0.2	Hdac1 interacts with fli1 and mediates its deacetylation / our previous studies have shown that pcaf-dependent acetylation of fli1 at lysine 380 decreases its protein stability / p300 promotes the interaction of fli1 with hdac1 and increases the dna binding ability of fli1 through deacetylation of lysine 380	SIGNOR-202689
Q01344	O60674	1	phosphorylation	up-regulates activity	0.602	Jak 2 is physically associated with the IL-5b receptor. The binding of IL-5 to its receptor results in tyrosine phosphorylation and activation of Jak 2 tyrosine kinase within 1 to 3 min.	SIGNOR-254352
Q13485	O14980	0	relocalization	down-regulates	0.3	We demonstrate that inhibition of crm1-mediated nuclear export by treatment of cells with leptomycin b results in endogenous smad4 accumulating very rapidly in the nucleus.	SIGNOR-84247
Q13131	P26358	1	phosphorylation	down-regulates activity	0.2	Together, these results indicate that AMPK phosphorylated DNMT1-Ser730, RBBP7-Ser314, and HAT1-Ser190\|AMPK decreased DNMT1 activity	SIGNOR-264783
Q06187	Q9UN19	1	phosphorylation	up-regulates activity	0.672	We present a number of lines of evidence that in vivo, Src-type tyrosine kinases are responsible for the phosphorylation of tyrosine 139 in DAPP-1. \| Although Btk appears to phosphorylate DAPP-1 relatively efficiently both in Sf9 cells and in vitro, we find no evidence that in either B cells or PAE cells Btk family kinases phosphorylate DAPP-1.	SIGNOR-250602
P59594	P07711	0	cleavage	up-regulates activity	0.2	A cell-free membrane-fusion system demonstrates that engagement of receptor followed by proteolysis is required for SARS-CoV membrane fusion and indicates that cathepsin L is sufficient to activate membrane fusion by SARS-CoV S. These results suggest that SARS-CoV infection results from a unique, three-step process: receptor binding and induced conformational changes in S glycoprotein followed by cathepsin L proteolysis within endosomes. The requirement for cathepsin L proteolysis identifies a previously uncharacterized class of inhibitor for SARS-CoV infection.	SIGNOR-260218
P53350	Q13315	0	phosphorylation	down-regulates activity	0.429	Indeed Chk2 mediates the degradation of Cdc25A to activate the S-phase checkpoint [5\u20137,18] , whereas ATM phosphorylates and inactivates Plk1, consolidating the delay in the entry into M phase [5\u201319] .\|Indeed Chk2 mediates the degradation of Cdc25A to activate the S-phase checkpoint [5-7,18], whereas ATM phosphorylates and inactivates Plk1, consolidating the delay in the entry into M phase [5-19].	SIGNOR-279793
P05771	P68104	1	phosphorylation	up-regulates activity	0.2	PKCβI phosphorylates eEF1A at Ser53.our proteomics exploration of cPKC signaling in the nuclei of C2C12 cells demonstrated that the up-regulation of eEF1A intranuclear content, evoked by insulin, is associated with an increase in the phosphorylation of the Ser53 residue of the protein.	SIGNOR-263167
O95180	P17612	0	phosphorylation	down-regulates activity	0.2	Here, we identify protein kinase A (PKA) as a molecular switch that allows Gbeta(2)gammax dimers to effect voltage-independent inhibition of Ca(v)3.2 channels. Inhibition requires phosphorylation of Ser(1107), a critical serine residue on the II-III loop of the channel pore protein. S1107A prevents inhibition of unitary currents by recombinant Gbeta(2)gamma(2) dimers but does not disrupt dimer binding nor change its specificity.	SIGNOR-263110
P06493	P15531	1	phosphorylation	up-regulates	0.266	Application of this approach to the discovery of cdk1-cyclin b substrates yielded identification of >70 substrates and phosphorylation sites. Many of these sites are known to be phosphorylated in vivo, but most of the proteins have not been characterized as cdk1-cyclin b substrates.	SIGNOR-160493
Q15797	P49336	0	phosphorylation	down-regulates	0.383	Phosphorylation of the linker region of smad1, a receptor-activated smad (r-smad), at serine 206 (s206) and s214 induced by bmp and mediated by cdk8/9 is critical for binding of the e3 ubiquitin ligase smurf1. Binding of smurf1 leads to polyubiquitination of smad1 and its degradation by the proteasome;cdk8 and cyclint-cdk9 showed a preference for s206 and s214 but also phosphorylated s186 and s195 in the case of smad1;and t179, s208 and s213 in the case of smad3.	SIGNOR-161626
P15336	P45983	0	phosphorylation	up-regulates	0.78	Activating transcription factor-2 (atf2) was found to be a target of the jnk signal transduction pathway. Atf2 was phosphorylated by jnk on two closely spaced threonine residues within the nh2-terminal activation domain.	SIGNOR-33914
O00141	O43524	1	phosphorylation	down-regulates activity	0.794	We show here that sgk1, like akt, promotes cell survival and that it does so in part by phosphorylating and inactivating fkhrl1. However, sgk and akt display differences with respect to the efficacy with which they phosphorylate the three regulatory sites on fkhrl1. While both kinases can phosphorylate thr-32, sgk displays a marked preference for ser-315 whereas akt favors ser-253.	SIGNOR-236607
Q96AX9	Q13546	1	ubiquitination	down-regulates quantity by destabilization	0.295	These data suggest that after binding, MIB2 inhibits RIPK1 through a mechanism that is dependent on the E3 ligase activity of MIB2.\|Whereas MIB2 readily ubiquitylated wild-type RIPK1, mutating K377 to R significantly reduced MIB2 mediated ubiquitylation of RIPK1 (XREF_SUPPLEMENTARY A).	SIGNOR-278633
Q04206	O14757	0	phosphorylation	up-regulates activity	0.454	Here we demonstrate that ARF induces the ATR- and Chk1-dependent phosphorylation of the RelA transactivation domain at threonine 505, a site required for ARF-dependent repression of RelA transcriptional activity.	SIGNOR-280225
P11217	Q16816	0	phosphorylation	up-regulates activity	0.684	It is well-characterized that GP is activated by PhK-mediated serine phosphorylation at Ser-15	SIGNOR-267398
O75874	P36888	0	phosphorylation	up-regulates activity	0.424	Moreover, in an in vitro kinase assay, purified recombinant FLT3 (rFLT3) phosphorylated recombinant IDH2 R140Q mutant but did not alter its catalytic activity (Figure 1C), whereas rFLT3 phosphorylated mIDH1 protein and enhanced its catalytic activity	SIGNOR-267630
Q9UKV8	P18031	0	dephosphorylation	down-regulates activity	0.2	Taken together, our results indicate that Tyr 393 of AGO2 is hyperphosphorylated in response to PTP1B inactivation and may contribute to H-RAS V12 -induced development of senescence.\|We identified phospho-Tyr 393 of argonaute 2 (AGO2) as a direct substrate of PTP1B.	SIGNOR-277120
Q14847	Q13976	0	phosphorylation	down-regulates activity	0.359	Studies with human lasp mutants identified serine 146 as a specific phosphorylation site for cgk and cak in vivo. Lasp is an actin-binding protein, and the phospho-lasp-mimicking mutant s146d showed reduced binding affinity for f-actin in cosedimentation experiments.	SIGNOR-97946
Q9NP71	Q9H5J4	1	transcriptional regulation	up-regulates quantity by expression	0.398	In this study, we clearly show that mouse and human Elovl6 are direct targets of ChREBP.	SIGNOR-267945
P10636	O15264	0	phosphorylation	down-regulates activity	0.531	Phosphorylation of tau by SAPK3 and SAPK4 resulted in a marked reduction in the ability of tau to promote microtubule assembly.	SIGNOR-278313
P06213	Q9HD43	0	dephosphorylation	down-regulates	0.27	These results, combined with secondary dephosphorylation tests, confirm and extend earlier findings that ptp-1b and t-cell ptp are physiological enzymes for the insulin receptor kinase	SIGNOR-76072
P12544	Q01105	1	cleavage	down-regulates	0.711	Gzma cleaved the nucleosome assembly protein set after lys176 and disrupted its nucleosome assembly activity.	SIGNOR-110462
Q05655	P49840	1	phosphorylation	down-regulates	0.342	Convergence of multiple signaling cascades at glycogen synthase kinase 3: edg receptor-mediated phosphorylation and inactivation by lysophosphatidic acid through a protein kinase c-dependent intracellular pathway.	SIGNOR-115722
Q9Y2R2	P20963	1	dephosphorylation	down-regulates activity	0.447	In vitro experiments with purified recombinant proteins demonstrated that PTPN22-D195A/C227S interacted directly with activated Lck, Zap70, and TCRzeta, confirming the initial substrate trap results. Native PTPN22 dephosphorylated Lck and Zap70 at their activating tyrosine residues Tyr-394 and Tyr-493, respectively, but not at the regulatory tyrosines Tyr-505 (Lck) or Tyr-319 (Zap70). Native PTPN22 also dephosphorylated TCRzeta in vitro and in cells, and its substrate trap variant co-immunoprecipitated with TCRzeta when both were coexpressed in 293T cells, establishing TCRzeta as a direct substrate of PTPN22.	SIGNOR-248837
Q14761	P68400	0	phosphorylation	up-regulates quantity by stabilization	0.2	We demonstrated for the first time that LPAP is a substrate for protein kinase CK2 that phosphorylates it at Ser153, presumably ensuring LPAP resistance to degradation.	SIGNOR-273629
Q04206	P08581	1	transcriptional regulation	up-regulates quantity	0.25	Together, these results indicate that the Met gene is a direct target of NFkappaB and that Met participates in NFkappaB-mediated cell survival.	SIGNOR-241929
Q13882	Q05397	1	phosphorylation	up-regulates activity	0.264	B. PTK6 phosphorylates FAK at tyrosine residue 861.\|Knockdown of PTK6 in the PC3 human prostate cancer cell line disrupts FAK and AKT activation and promotes anoikis, which can be rescued by exogenous expression of FAK.	SIGNOR-278428
Q9Y4K3	Q99538	1	polyubiquitination	up-regulates quantity by stabilization	0.307	We demonstrate that TRAF6 ubiquitinates the proform of AEP through K63-linked polyubiquitin, reversible by USP17, and forms a complex with HSP90α to subsequently promote pro-AEP intracellular stability as well as secretion. We now present evidence that AEP is a substrate for TRAF6 ubiquitination, resulting in AEP/TRAF6/HSP90α complex formation.	SIGNOR-272853
P17252	Q15121	1	phosphorylation	down-regulates	0.384	Pea-15 is phosphorylated on two ser residues, ser104 and ser116. Protein kinase c (pkc) phosphorylates ser104 / we report that phosphorylation of pea-15 blocks its interaction with erk1/2 in vitro and in vivo and that phosphorylation of both ser104 and ser116 is required for this effect.	SIGNOR-137841
P37231	Q00535	0	phosphorylation	down-regulates activity	0.574	CDK5 in turn phosphorylates PPARgamma at Ser273 and prevents the transcription of specific PPARgamma target genes that have anti-diabetic effects .	SIGNOR-278189
Q13131	Q92538	1	phosphorylation	down-regulates	0.2	These results indicate that gbf1 is a novel ampk substrate and that the ampk-mediated phosphorylation of gbf1 at thr(1337) has a critical role, presumably by attenuating the function of gbf1, in the disassembly of the golgi apparatus induced under stress conditions that lower the intracellular atp concentration.	SIGNOR-159639
P53667	Q13464	0	phosphorylation	up-regulates activity	0.617	Rho-associated kinase rock activates lim-kinase 1 by phosphorylation at threonine 508 within the activation loop.	SIGNOR-74569
Q15418	Q05195	1	phosphorylation	down-regulates	0.315	In this study, we showed that mad1 is a substrate of p90 ribosomal kinase (rsk) and p70 s6 kinase (s6k). Both rsk and s6k phosphorylate serine 145 of mad1 upon serum or insulin stimulation. Ser-145 phosphorylation of mad1 accelerates the ubiquitination and degradation of mad1 through the 26s proteasome pathway	SIGNOR-178586
Q9NQT8	Q7KZI7	0	phosphorylation	down-regulates activity	0.415	We report here the identification of GAKIN/KIF13B as a novel in vivo substrate for Par1b and present evidence that GAKIN/KIF13B plays a critical role in axon formation in neurons, which is negatively regulated by Par1b-mediated phosphorylation. Par1b phosphorylates GAKIN/KIF13B at both Ser1381 and Ser1410.	SIGNOR-262956
Q92769	P00519	0	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
P12004	Q14527	0	ubiquitination	up-regulates activity	0.78	HLTF promotes the Lys-63-linked polyubiquitination of proliferating cell nuclear antigen (PCNA) that is required for maintaining genomic stability.	SIGNOR-278608
P06493	Q8N884	1	phosphorylation	down-regulates activity	0.2	The major mitotic kinase CDK1-cyclin B complex phosphorylates human cGAS at S305 or mouse cGAS at S291, which inhibits its ability to synthesize cGAMP upon mitotic entry.	SIGNOR-276526
Q15722	P43250	0	phosphorylation	down-regulates activity	0.474	Thr(308) is a major residue involved in GRK6-mediated desensitization of BLT1 signaling.	SIGNOR-251213
Q9UHR4	P12931	0	phosphorylation	up-regulates activity	0.389	Here, we report that overexpression of IRTKS increases the speed of wound closure of HT1080 cells in a Src-dependent manner. Active Src phosphorylates IRTKS in vivo and in vitro. Deletion mapping and mutation analysis revealed that six tyrosine residues (Y37, Y156, Y163, Y274, Y293 and Y439) were Src-stimulated phosphorylation sites on IRTKS. Disruption of Src-stimulated IRTKS phosphorylation abolished the effect of IRTKS on wound closure. Collectively, these data suggest Src-stimulated IRTKS phosphorylation is essential for its function in cell motility.	SIGNOR-263041
Q12778	Q99576	0	relocalization	down-regulates activity	0.301	GILZ inhibits FOXO1, FOXO3, and FOXO4 transcriptional activities measured with natural or synthetic FOXO-responsive promoters in HL-60 cells.	SIGNOR-256146
Q96J92	P55017	1	phosphorylation	up-regulates activity	0.579	Threonine 48 was identified as the WNK4 phosphorylation site at mouse NCC\|. Thus, WNK4 stimulates NCC in three ways: (1) direct phosphorylation and in turn increasing NCC protein abundance; (2) facilitating the phosphorylation of NCC by SPAK/OSR1 indirectly, and (3) phosphorylating and activating SPAK/OSR1.\|Evidences from early studies using Xenopus oocytes and mammalian cells indicate that WNK4 inhibits NCC and PHAII-causing mutations relieve the inhibition	SIGNOR-264631
Q96TA1	P00533	0	phosphorylation	up-regulates activity	0.2	We demonstrate here that activated EGFR phosphorylates the Y593 residue of the protein known as family with sequence similarity 129, member B (FAM129B), which is overexpressed in many types of human cancer. FAM129B phosphorylation increased the interaction between FAM129B and Ras, resulting in reduced binding of p120-RasGAP to Ras.	SIGNOR-273637
O14733	P53779	1	phosphorylation	up-regulates	0.582	Two mapkks, sek1 and mkk7, synergistically activate jnk. Sek1 prefers the tyr-185 residue, and mkk7 prefers the thr-183 residue (17, 19).	SIGNOR-137609
Q9GZY8	O00429	1	relocalization	up-regulates activity	0.601	Mff functions as an essential factor in mitochondrial recruitment of Drp1.	SIGNOR-245957
P49715	Q16549	0	phosphorylation	down-regulates	0.2	Addition of active p38a induced phosphorylation of wild-type c/ebp_? (c/ebp_?WT) on serine 21	SIGNOR-186202
P46060	O75592	1	relocalization	down-regulates quantity by destabilization	0.315	SUMOylated RanGAP1 Inhibits MYCBP2 Activity and Mediates Its Transport to the Nucleus. Surprisingly, we did not find MYCBP2-dependent ubiquitylation of SUMOylated RanGAP1 but instead a strong inhibition of the ubiquitin ligase activity of MYCBP2 in the presence of SUMOylated RanGAP1, as determined by the presence of ubiquitylated proteins. this effect was specific for SUMOylated RanGAP1, because the unmodified form of RanGAP1 did not affect MYCBP2-dependent protein ubiquitylation. , SUMOylated RanGAP1 inhibited the ubiquitin ligase activity of MYCBP2, and it is tempting to speculate that SUMOylated RanGAP1 inhibits the ubiquitin ligase activity of MYCBP2 to ensure MYCBP2 silencing during its transport to the nucleus	SIGNOR-261203
O95747	Q13153	1	phosphorylation	down-regulates activity	0.382	OSR1 phosphorylated threonine 84 in the N-terminal regulatory domain of PAK1. phosphorylation of PAK1 by OSR1 desensitizes PAK1 to activation by small G proteins, providing a modulatory input to PAK1 activity.	SIGNOR-250210
Q96KB5	Q8TBB1	0	ubiquitination	down-regulates quantity by destabilization	0.375	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.	SIGNOR-272898
Q99986	Q9H4B4	0	phosphorylation	up-regulates	0.474	Vrk1 does not phosphorylate plk3, but plk3 phosphorylates the c-terminal region of vrk1 in ser342. Vrk1 with substitutions in s342 is catalytically active but blocks golgi fragmentation, indicating that its specific phosphorylation is necessary for this process.	SIGNOR-182858
P27361	P33076	1	phosphorylation	up-regulates	0.341	We found that in these cells, lipopolysaccharide stimulates the expression of mhc ii genes via the activation of erk1/2, which is mediated by toll-like receptor 4. Erk1/2 then phosphorylates the serine at position 357, which is located in a degron of ciita isoform 1 that leads to its monoubiquitylation.	SIGNOR-150545
Q8NFH5	P06493	0	phosphorylation	down-regulates activity	0.563	Collectively, these data show that mitotic hyperphosphorylation of Nup53 by CDK1 and PLK1 contributes to its removal from NPCs.\|The combined mutation of the CDK1 and PLK1 sites to phosphomimetic residues almost completely abolished NPC integration of Nup53, indicating that hyperphosphorylation of Nup53 might be incompatible with its NPC association.	SIGNOR-278917
P16949	O96013	0	phosphorylation	down-regulates activity	0.283	Indeed, we show here that inactivating phosphorylation of the endogenous stathmin on serine-16 is also induced by the active PAK4 in mitotic egg extract and is likely to participate in the observed stabilization of the MT asters ( xref , right).	SIGNOR-280058
P31749	Q06187	1	phosphorylation	down-regulates quantity by destabilization	0.296	The activated serine/threonine kinase Akt/protein kinase B (PKB) phosphorylated Btk on two sites prior to 14-3-3ζ binding. The interaction sites were mapped to phosphoserine pS51 in the pleckstrin homology domain and phosphothreonine pT495 in the kinase domain.	SIGNOR-276466
Q13153	Q15746	1	phosphorylation	down-regulates activity	0.556	P21-activated kinase 1 (PAK1) phosphorylates MLCK, resulting in decreased MLCK activity.	SIGNOR-250317
P45983	P04150	1	phosphorylation	down-regulates	0.638	Taken together, these findings suggest that jnk-mediated phosphorylation of the gr-ser226 enhances gr nuclear export and may contribute to termination of gr-mediated transcription.	SIGNOR-93558
P08243	P08047	0	transcriptional regulation	up-regulates quantity by expression	0.2	Sp1 and Sp3 Activate Transcription Driven by the AS Promoter	SIGNOR-268019
P11362	O15530	1	phosphorylation	up-regulates activity	0.2	Y105 phosphorylation of PKM2, which is involved in FGFR1-regulated PDHK1 expression, appears to be an upstream event that precedes FGFR1-dependent phosphorylation and activation of PDHK1 in cancer cell metabolism.	SIGNOR-279174
P09874	P78527	0	phosphorylation	down-regulates activity	0.525	Therefore, through its interaction with Ku70/80 in the presence of dsDNA , DNA-PK phosphorylated PARP-1 at its catalytic CTD.	SIGNOR-280093
Q9BZL6	Q9GZY8	1	phosphorylation	up-regulates activity	0.2	The mitochondrial fission factor (MFF), the main mitochondrial receptor for the Dynamin-related protein 1 (DRP1), is directly phosphorylated by Protein Kinase D (PKD) specifically during mitosis. PKD-dependent MFF phosphorylation is required and sufficient for mitochondrial fission in mitotic but not in interphasic cells.\|PKD directly phosphorylates MFF on serines 155, 172, and 275	SIGNOR-275947
Q03060	P06493	0	phosphorylation	down-regulates quantity by destabilization	0.296	The MAPKs extracellular signal-regulated kinases 1 and 2 physically interact with ICER and mediated the phosphorylation of ICER on a critical serine residue (Ser-41). A mutant form of ICER in which Ser-41 was substituted by alanine had a half-life 4-5 h longer than its wild-type counterpart. This alteration in stability was due to the inability of the Ser-41-mutant ICER to be efficiently ubiquitinated and degraded via the ubiquitin-proteasome pathway.	SIGNOR-275979
Q00535	P00519	0	phosphorylation	up-regulates activity	0.585	Phosphorylation of Cdk5 by c-Abl occurs on tyrosine 15 (Y15), which is stimulatory for p35/Cdk5 kinase activity.	SIGNOR-245288
P31749	O60343	1	phosphorylation	down-regulates	0.764	Recently, we identified a 160-kda protein in adipocytes, designated as160, that is phosphorylated by the insulin-activated kinase akt	SIGNOR-252594
Q15672	O14920	0	phosphorylation	down-regulates activity	0.332	Hence, our current study supports the pivotal role of beta-TRCP in IKKbeta mediated Twist degradation.\|More importantly, IKK\u03b2-dependent phosphorylation of Twist at T125 and S127 governs its nuclear localization.	SIGNOR-278404
P15374	P62987	1	cleavage	up-regulates quantity	0.801	Here we provide data suggesting that two of the four mammalian ubiquitin precursors, UBA52 and UBA80, are processed mostly post-translationally whereas the other two, UBB and UBC, probably undergo a combination of co- and post-translational processing. Using an unbiased biochemical approach we found that UCHL3, USP9X, USP7, USP5 and Otulin/Gumby/FAM105b are by far the most active DUBs acting on these precursors.	SIGNOR-270827
P04637	P11166	1	transcriptional regulation	down-regulates quantity by repression	0.597	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-267464
Q05655	P67775	0	dephosphorylation	down-regulates activity	0.377	PP2A(c) displayed the highest specific activity towards PKCdelta. The role of PP2A(c) in the dephosphorylation of PKCdelta in cells was supported by the demonstration that these proteins could be co-immunoprecipitated from NIH3T3 cells.\|In conclusion, the evidence here indicates that PKCdelta de-phosphorylation and hence inactivation is effected by PP2A with which it forms a complex	SIGNOR-248638
Q8N392	Q6P5Z2	0	phosphorylation	up-regulates activity	0.2	We present strong evidence that PKN3-ARHGAP18 interaction is increased upon ARHGAP18 phosphorylation and that the phosphorylation of ARHGAP18 by PKN3 enhances its GAP domain activity and contributes to negative regulation of active RhoA.\|These results support our data from phosphoproteomic screen and suggest that ARHGAP18 can be phosphorylated by PKN3 on Thr154, Ser156 and Thr158.	SIGNOR-264572
Q07955	P49761	0	phosphorylation	up-regulates activity	0.531	In vitro, Clk/Sty efficiently phosphorylated the SR family member ASF/SF2 on serine residues located within its serine/arginine-rich region (the RS domain). Overexpression of the active Clk/Sty kinase caused a redistribution of SR proteins within the nucleus. These results suggest that Clk/Sty kinase directly regulates the activity and compartmentalization of SR splicing factors.	SIGNOR-273859
Q9Y297	P30304	1	ubiquitination	up-regulates	0.494	Scfb-trcp has recently been shown to degrade phosphorylated cdc25a in the s and g2 phases.	SIGNOR-128436
Q96GD4	P04637	1	phosphorylation	down-regulates	0.719	We show that aurora b phosphorylates p53 at s183, t211, and s215 to accelerate the degradation of p53 through the polyubiquitination-proteasome pathway, thus functionally suppressing the expression of p53 target genes involved in cell cycle inhibition and apoptosis (e.g., p21 and puma).	SIGNOR-197598
P30305	P45983	0	phosphorylation	down-regulates quantity by destabilization	0.284	Recently, we showed that Cdc25B is degraded rapidly by non-genotoxic stimuli that activate stress-responsive MAPKs, such as Jun N-terminal kinase (JNK) and p38 (Uchida et al., 2009). Our results suggested that these kinases phosphorylate specific Ser residues in the N-terminal region (S101 and S103) to induce Cdc25B degradation.Here, we report that Cdc25B was ubiquitylated by SCF(βTrCP) E3 ligase upon phosphorylation at two Ser residues in the βTrCP-binding-motif-like sequence D(94)AGLCMDSPSP(104).	SIGNOR-276352
Q13153	O14965	1	phosphorylation	up-regulates	0.417	The upstream pak1 kinase can phosphorylate aurora a at t288, autophosphorylation appears to be the essential mode of activation. Our experiments suggest that phosphorylation of t288 is important for regulation of the aurora2 kinase both for its activity and its stability	SIGNOR-205110
O95147	Q15750	1	dephosphorylation	down-regulates activity	0.298	DUSP14 directly interacted with TGF-beta-activated kinase 1 (TAK1)-binding protein 1 (TAB1) and dephosphorylated TAB1 at Ser (438), leading to TAB1 and TAK1 complex inactivation in T cells.	SIGNOR-277147
Q16543	P19784	0	phosphorylation	up-regulates activity	0.489	Phosphorylation of serine 13 is required for the proper function of the Hsp90 co-chaperone, Cdc37. \| In this report, we demonstrate that mammalian Cdc37 is phosphorylated on Ser13 in situ in rabbit reticulocyte lysate and in cultured K562 cells and that casein kinase II is capable of quantitatively phosphorylating recombinant Cdc37 at this site.	SIGNOR-250982
P35568	P06213	0	phosphorylation	up-regulates activity	0.914	All known IRS proteins contain multiple YXXM motifs that upon phosphorylation by activated insulin receptors A previous study using phosphopeptides suggested that tyrosine-phosphorylated YXXM motifs at positions 608 and 939 in rat IRS-1 bind with high affinity to SH2 domains of p85, and motifs at positions 460 and 987 bind with lower affinity (10).	SIGNOR-235975
Q5FBB7	P0C0S8	0	relocalization	up-regulates activity	0.2	The complex between shugoshin and protein phosphatase 2A (Sgo1-PP2A) localizes to centromeres in mitosis, binds to cohesin in a reaction requiring Cdk-dependent phosphorylation of Sgo1, dephosphorylates cohesin-bound sororin, and protects a centromeric pool of cohesin from mitotic kinases and the cohesin inhibitor Wapl.\|The centromeric localization of Sgo1 requires histone H2A phosphorylation at T120 (H2A-pT120) by the kinase Bub1.	SIGNOR-265262
P06493	Q8NHV4	1	phosphorylation	up-regulates activity	0.585	Here we report that the function of Nedd1 is regulated by Cdk1 and Plk1. During mitosis, Nedd1 is firstly phosphorylated at T550 by Cdk1, which creates a binding site for the polo-box domain of Plk1. Then, Nedd1 is further phosphorylated by Plk1 at four sites: T382, S397, S637 and S426. The sequential phosphorylation of Nedd1 by Cdk1 and Plk1 promotes its interaction with gamma-tubulin for targeting the gammaTuRC to the centrosome and is important for spindle formation.	SIGNOR-272973
P00519	P43351	1	phosphorylation	up-regulates activity	0.685	C-Abl tyrosine kinase associates with and phosphorylates Rad52 on tyrosine 104. he functional significance of c-Abl-dependent phosphorylation of Rad52 is underscored by our findings that cells that express the phosphorylation-resistant Rad52 mutant, in which tyrosine 104 is replaced by phenylalanine, exhibit compromised nuclear foci formation in response to IR.	SIGNOR-251435
P25098	P30559	1	phosphorylation	down-regulates activity	0.2	Recent experiments in COS-7 cells transfected with OTR have demonstrated that a rapid GRK2-mediated phosphorylation of the agonist-occupied OTR is a key first step leading to its desensitization, and that it precedes and is required for β-arrestin-dependent internalization	SIGNOR-270329
Q99683	P46734	1	phosphorylation	up-regulates activity	0.599	Ask1 is a member of a mapkkk family and functions as an upstream kinase engaged in c-jun nh2-terminal kinase (jnk)/p38 signaling via the phosphorylation and activation of mapkks, such as mkk3, -4, -6, and -7	SIGNOR-161763
P49910	O15105	1	transcriptional regulation	down-regulates quantity by repression	0.2	ZNF165 drives the unrestrained activation of transforming growth factor β (TGFβ) signalling by directly inactivating the expression of negative feedback pathway regulators, SMURF2, SMAD7 and PMEPA1.	SIGNOR-266093
P54829	P06241	1	dephosphorylation	down-regulates	0.527	Wild-type step(61) dephosphorylates fyn at tyr(420) but not at tyr(531). These results suggest that step regulates the activity of fyn by specifically dephosphorylating the regulatory tyr(420) and may be one mechanism by which fyn activity is decreased within psds.	SIGNOR-86791
P35228	P42224	0	transcriptional regulation	up-regulates quantity by expression	0.428	STAT1 binds as a homodimer to cis elements known as gammaactivated sequences in the promoters of the genes encoding NOS2, the MHC class II transactivator (CIITA) and IL-12, among others.	SIGNOR-249497
P04637	Q16539	0	phosphorylation	up-regulates activity	0.773	P38 regulates p53, but also in p53-defective tumor cells rewire their checkpoint response and become dependent in the p38/mk2 pathway in mcf-7 cells, p38 kinase activated p53 more effectively than other members of the ras pathway. p53 and p38 kinase exist in the same physical complex, and co-expression of p38 stabilized p53 protein. In vitro, p38 kinase phosphorylated p53 at ser33 and ser46, a newly identified site.	SIGNOR-155246
P53778	Q16875	1	phosphorylation	up-regulates quantity	0.2	KRAS transformation and overexpression of p38gamma increased expression of PFKFB3 and glucose transporter GLUT2	SIGNOR-279539
O60341	P17252	0	phosphorylation	up-regulates activity	0.352	Together, these data indicate that LPS-induced LSD1 phosphorylation by PKC\u03b1 is required for its interaction with p65 in the nucleus.\|We have previously reported that LSD1 is phosphorylated by PKCalpha on serine 112 site, and knockin mice bearing phosphorylation defective Lsd1 SA/SA alleles show altered circadian rhythms and impaired phase resetting (Nam et al., 2014).	SIGNOR-279425

Q32MZ4

P43405

0

phosphorylation

up-regulates activity

0.2

However, this inhibitory activity TRIP can be reversed by the co-expression of Syk, which might inhibit the activity of cytoplasmic TRIP, sequester TRIP from important nucleolar targets or even counter TRIP 's inhibitory effects on TRAF and TNF signaling by regulating the activity of alternative components of the pathway.|Syk induces phosphorylation of TRIP on tyrosine.

SIGNOR-279297

P28482

P24723

0

phosphorylation

up-regulates activity

0.506

Protein kinase C-eta regulates Mcl-1 level via ERK1. knockdown of PKCη but not PKCα, -δ or -ε caused a significant decrease in ERK (extracellular signal-regulated kinase) phosphorylation. Knockdown of ERK1 but not ERK2 decreased Mcl-1 level, and the decrease in Mcl-1 caused by PKCη knockdown was restored by ERK1 overexpression. These results suggest that PKCη utilizes the ERK signaling pathway to protect against ubiquitin-mediated proteasomal degradation of Mcl-1.

SIGNOR-261910

Q04206

P11309

0

phosphorylation

up-regulates

0.2

In this study we show that phosphorylation of rela/p65 at ser276 prevents its degradation by ubiquitin-mediated proteolysis. importantly, we identify pim-1 as a further kinase responsible for the phosphorylation of rela/p65 at ser276.

SIGNOR-189125

Q13480

P27361

0

phosphorylation

up-regulates activity

0.633

Our results demonstrate that ERK1/2 phosphorylate Gab1 at six serine/threonine residues (T312, S381, S454, T476, S581, S597) in consensus motifs for MAP kinase phosphorylation. |serine and threonine phosphorylation are capable of modulating the initial signal

SIGNOR-249464

Q63HK5

Q13547

1

relocalization

up-regulates activity

0.2

We carried out yeast two-hybrid studies with a PTB domain of FE65, focusing on those genes that might be involved in nuclear signaling, and identified and validated Teashirt proteins as FE65 interacting proteins in neurons. Using reporter systems, we observed that FE65 could simultaneously recruit SET, a component of the inhibitor of acetyl transferase, and Teashirt, which in turn recruited histone deacetylases, to produce a powerful gene-silencing complex.Endogenous HDAC1 was co-immunoprecipitated with FE65 when both FE65 and Teashirt3 were co-transfected (lane 4), but not when Teashirt3 or FE65 was omitted (lane 5 and 6), confirming that the association of HDAC1 with FE65 is dependent on, and mediated, by Teashirt3.

SIGNOR-264814

P46937

Q4VCS5

0

relocalization

down-regulates

0.734

Yap/taz and angiomotin (amot) family proteins were shown to interact, resulting in yap/taz localization to tight junctions and inhibition through phosphorylation-dependent and -independent mechanisms.

SIGNOR-175779

P30305

P53350

0

phosphorylation

up-regulates activity

0.663

These data indicated that PLK1 phosphorylates CDC25B and that pre-phosphorylation of CDC25B by CDK1/CyclinB enhances its substrate properties for PLK1 in vitro

SIGNOR-267560

P24941

Q99728

1

phosphorylation

down-regulates activity

0.609

CDK2-cyclin A1/E1 and CDK1-cyclin B1 phosphorylate BARD1 on its NH(2) terminus in vivo and in vitro. 44999999="E1" 45999998="terminus"}|Here we show that the ubiquitin ligase activity of BRCA1-BARD1 is down-regulated by CDK2.

SIGNOR-280211

Q05655

Q16658

1

phosphorylation

down-regulates activity

0.324

Phosphorylation of human fascin inhibits its actin binding and bundling activities.

SIGNOR-248944

Q9Y5A7

Q00987

0

ubiquitination

up-regulates activity

0.276

Our results rather suggest that Mdm2 specifically ubiquitinates NUB1 on lysine 159 and that this modification is required for NUB1 functions.|We conclude that Mdm2 acts as a positive regulator of NUB1 function, by modulating NUB1 ubiquitination on lysine 159.

SIGNOR-278556

P17275

P49841

0

phosphorylation

down-regulates quantity by destabilization

0.2

Thus, JunB phosphorylation at S251 and T255 by GSK3β is primed by phosphorylation at S259 by a yet to-be-identified kinase.Phosphorylation at S251, T255 and S259 is required for JunB degradation.

SIGNOR-276417

Q9UDY8

Q5T447

0

polyubiquitination

up-regulates quantity by stabilization

0.366

HECTD3 promotes MALT1 ubiquitination with nondegradative polyubiquitin chains by direct interacting with the MALT1 through its N-terminal destruction of cyclin domain. HECTD3 does not target MALT1 for degradation but stabilize it.

SIGNOR-272096

Q9HCE7

Q13243

1

ubiquitination

down-regulates quantity by destabilization

0.262

K125 was also the major site of SRSF5 ubiquitylation mediated by Smurf1.|Smurf1 targets SRSF5 for degradation upon low glucose

SIGNOR-278665

Q13547

Q01543

1

deacetylation

up-regulates

0.2

Hdac1 interacts with fli1 and mediates its deacetylation / our previous studies have shown that pcaf-dependent acetylation of fli1 at lysine 380 decreases its protein stability / p300 promotes the interaction of fli1 with hdac1 and increases the dna binding ability of fli1 through deacetylation of lysine 380

SIGNOR-202689

Q01344

O60674

1

phosphorylation

up-regulates activity

0.602

Jak 2 is physically associated with the IL-5b receptor. The binding of IL-5 to its receptor results in tyrosine phosphorylation and activation of Jak 2 tyrosine kinase within 1 to 3 min.

SIGNOR-254352

Q13485

O14980

0

relocalization

down-regulates

0.3

We demonstrate that inhibition of crm1-mediated nuclear export by treatment of cells with leptomycin b results in endogenous smad4 accumulating very rapidly in the nucleus.

SIGNOR-84247

Q13131

P26358

1

phosphorylation

down-regulates activity

0.2

Together, these results indicate that AMPK phosphorylated DNMT1-Ser730, RBBP7-Ser314, and HAT1-Ser190|AMPK decreased DNMT1 activity

SIGNOR-264783

Q06187

Q9UN19

1

phosphorylation

up-regulates activity

0.672

We present a number of lines of evidence that in vivo, Src-type tyrosine kinases are responsible for the phosphorylation of tyrosine 139 in DAPP-1. | Although Btk appears to phosphorylate DAPP-1 relatively efficiently both in Sf9 cells and in vitro, we find no evidence that in either B cells or PAE cells Btk family kinases phosphorylate DAPP-1.

SIGNOR-250602

P59594

P07711

0

cleavage

up-regulates activity

0.2

A cell-free membrane-fusion system demonstrates that engagement of receptor followed by proteolysis is required for SARS-CoV membrane fusion and indicates that cathepsin L is sufficient to activate membrane fusion by SARS-CoV S. These results suggest that SARS-CoV infection results from a unique, three-step process: receptor binding and induced conformational changes in S glycoprotein followed by cathepsin L proteolysis within endosomes. The requirement for cathepsin L proteolysis identifies a previously uncharacterized class of inhibitor for SARS-CoV infection.

SIGNOR-260218

P53350

Q13315

0

phosphorylation

down-regulates activity

0.429

Indeed Chk2 mediates the degradation of Cdc25A to activate the S-phase checkpoint [5\u20137,18] , whereas ATM phosphorylates and inactivates Plk1, consolidating the delay in the entry into M phase [5\u201319] .|Indeed Chk2 mediates the degradation of Cdc25A to activate the S-phase checkpoint [5-7,18], whereas ATM phosphorylates and inactivates Plk1, consolidating the delay in the entry into M phase [5-19].

SIGNOR-279793

P05771

P68104

1

phosphorylation

up-regulates activity

0.2

PKCβI phosphorylates eEF1A at Ser53.our proteomics exploration of cPKC signaling in the nuclei of C2C12 cells demonstrated that the up-regulation of eEF1A intranuclear content, evoked by insulin, is associated with an increase in the phosphorylation of the Ser53 residue of the protein.

SIGNOR-263167

O95180

P17612

0

phosphorylation

down-regulates activity

0.2

Here, we identify protein kinase A (PKA) as a molecular switch that allows Gbeta(2)gammax dimers to effect voltage-independent inhibition of Ca(v)3.2 channels. Inhibition requires phosphorylation of Ser(1107), a critical serine residue on the II-III loop of the channel pore protein. S1107A prevents inhibition of unitary currents by recombinant Gbeta(2)gamma(2) dimers but does not disrupt dimer binding nor change its specificity.

SIGNOR-263110

P06493

P15531

1

phosphorylation

up-regulates

0.266

Application of this approach to the discovery of cdk1-cyclin b substrates yielded identification of >70 substrates and phosphorylation sites. Many of these sites are known to be phosphorylated in vivo, but most of the proteins have not been characterized as cdk1-cyclin b substrates.

SIGNOR-160493

Q15797

P49336

0

phosphorylation

down-regulates

0.383

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

SIGNOR-161626

P15336

P45983

0

phosphorylation

up-regulates

0.78

Activating transcription factor-2 (atf2) was found to be a target of the jnk signal transduction pathway. Atf2 was phosphorylated by jnk on two closely spaced threonine residues within the nh2-terminal activation domain.

SIGNOR-33914

O00141

O43524

1

phosphorylation

down-regulates activity

0.794

We show here that sgk1, like akt, promotes cell survival and that it does so in part by phosphorylating and inactivating fkhrl1. However, sgk and akt display differences with respect to the efficacy with which they phosphorylate the three regulatory sites on fkhrl1. While both kinases can phosphorylate thr-32, sgk displays a marked preference for ser-315 whereas akt favors ser-253.

SIGNOR-236607

Q96AX9

Q13546

1

ubiquitination

down-regulates quantity by destabilization

0.295

These data suggest that after binding, MIB2 inhibits RIPK1 through a mechanism that is dependent on the E3 ligase activity of MIB2.|Whereas MIB2 readily ubiquitylated wild-type RIPK1, mutating K377 to R significantly reduced MIB2 mediated ubiquitylation of RIPK1 (XREF_SUPPLEMENTARY A).

SIGNOR-278633

Q04206

O14757

0

phosphorylation

up-regulates activity

0.454

Here we demonstrate that ARF induces the ATR- and Chk1-dependent phosphorylation of the RelA transactivation domain at threonine 505, a site required for ARF-dependent repression of RelA transcriptional activity.

SIGNOR-280225

P11217

Q16816

0

phosphorylation

up-regulates activity

0.684

It is well-characterized that GP is activated by PhK-mediated serine phosphorylation at Ser-15

SIGNOR-267398

O75874

P36888

0

phosphorylation

up-regulates activity

0.424

Moreover, in an in vitro kinase assay, purified recombinant FLT3 (rFLT3) phosphorylated recombinant IDH2 R140Q mutant but did not alter its catalytic activity (Figure 1C), whereas rFLT3 phosphorylated mIDH1 protein and enhanced its catalytic activity

SIGNOR-267630

Q9UKV8

P18031

0

dephosphorylation

down-regulates activity

0.2

Taken together, our results indicate that Tyr 393 of AGO2 is hyperphosphorylated in response to PTP1B inactivation and may contribute to H-RAS V12 -induced development of senescence.|We identified phospho-Tyr 393 of argonaute 2 (AGO2) as a direct substrate of PTP1B.

SIGNOR-277120

Q14847

Q13976

0

phosphorylation

down-regulates activity

0.359

Studies with human lasp mutants identified serine 146 as a specific phosphorylation site for cgk and cak in vivo. Lasp is an actin-binding protein, and the phospho-lasp-mimicking mutant s146d showed reduced binding affinity for f-actin in cosedimentation experiments.

SIGNOR-97946

Q9NP71

Q9H5J4

1

transcriptional regulation

up-regulates quantity by expression

0.398

In this study, we clearly show that mouse and human Elovl6 are direct targets of ChREBP.

SIGNOR-267945

P10636

O15264

0

phosphorylation

down-regulates activity

0.531

Phosphorylation of tau by SAPK3 and SAPK4 resulted in a marked reduction in the ability of tau to promote microtubule assembly.

SIGNOR-278313

P06213

Q9HD43

0

dephosphorylation

down-regulates

0.27

These results, combined with secondary dephosphorylation tests, confirm and extend earlier findings that ptp-1b and t-cell ptp are physiological enzymes for the insulin receptor kinase

SIGNOR-76072

P12544

Q01105

1

cleavage

down-regulates

0.711

Gzma cleaved the nucleosome assembly protein set after lys176 and disrupted its nucleosome assembly activity.

SIGNOR-110462

Q05655

P49840

1

phosphorylation

down-regulates

0.342

Convergence of multiple signaling cascades at glycogen synthase kinase 3: edg receptor-mediated phosphorylation and inactivation by lysophosphatidic acid through a protein kinase c-dependent intracellular pathway.

SIGNOR-115722

Q9Y2R2

P20963

1

dephosphorylation

down-regulates activity

0.447

In vitro experiments with purified recombinant proteins demonstrated that PTPN22-D195A/C227S interacted directly with activated Lck, Zap70, and TCRzeta, confirming the initial substrate trap results. Native PTPN22 dephosphorylated Lck and Zap70 at their activating tyrosine residues Tyr-394 and Tyr-493, respectively, but not at the regulatory tyrosines Tyr-505 (Lck) or Tyr-319 (Zap70). Native PTPN22 also dephosphorylated TCRzeta in vitro and in cells, and its substrate trap variant co-immunoprecipitated with TCRzeta when both were coexpressed in 293T cells, establishing TCRzeta as a direct substrate of PTPN22.

SIGNOR-248837

Q14761

P68400

0

phosphorylation

up-regulates quantity by stabilization

0.2

We demonstrated for the first time that LPAP is a substrate for protein kinase CK2 that phosphorylates it at Ser153, presumably ensuring LPAP resistance to degradation.

SIGNOR-273629

Q04206

P08581

1

transcriptional regulation

up-regulates quantity

0.25

Together, these results indicate that the Met gene is a direct target of NFkappaB and that Met participates in NFkappaB-mediated cell survival.

SIGNOR-241929

Q13882

Q05397

1

phosphorylation

up-regulates activity

0.264

B. PTK6 phosphorylates FAK at tyrosine residue 861.|Knockdown of PTK6 in the PC3 human prostate cancer cell line disrupts FAK and AKT activation and promotes anoikis, which can be rescued by exogenous expression of FAK.

SIGNOR-278428

Q9Y4K3

Q99538

1

polyubiquitination

up-regulates quantity by stabilization

0.307

We demonstrate that TRAF6 ubiquitinates the proform of AEP through K63-linked polyubiquitin, reversible by USP17, and forms a complex with HSP90α to subsequently promote pro-AEP intracellular stability as well as secretion. We now present evidence that AEP is a substrate for TRAF6 ubiquitination, resulting in AEP/TRAF6/HSP90α complex formation.

SIGNOR-272853

P17252

Q15121

1

phosphorylation

down-regulates

0.384

Pea-15 is phosphorylated on two ser residues, ser104 and ser116. Protein kinase c (pkc) phosphorylates ser104 / we report that phosphorylation of pea-15 blocks its interaction with erk1/2 in vitro and in vivo and that phosphorylation of both ser104 and ser116 is required for this effect.

SIGNOR-137841

P37231

Q00535

0

phosphorylation

down-regulates activity

0.574

CDK5 in turn phosphorylates PPARgamma at Ser273 and prevents the transcription of specific PPARgamma target genes that have anti-diabetic effects .

SIGNOR-278189

Q13131

Q92538

1

phosphorylation

down-regulates

0.2

These results indicate that gbf1 is a novel ampk substrate and that the ampk-mediated phosphorylation of gbf1 at thr(1337) has a critical role, presumably by attenuating the function of gbf1, in the disassembly of the golgi apparatus induced under stress conditions that lower the intracellular atp concentration.

SIGNOR-159639

P53667

Q13464

0

phosphorylation

up-regulates activity

0.617

Rho-associated kinase rock activates lim-kinase 1 by phosphorylation at threonine 508 within the activation loop.

SIGNOR-74569

Q15418

Q05195

1

phosphorylation

down-regulates

0.315

In this study, we showed that mad1 is a substrate of p90 ribosomal kinase (rsk) and p70 s6 kinase (s6k). Both rsk and s6k phosphorylate serine 145 of mad1 upon serum or insulin stimulation. Ser-145 phosphorylation of mad1 accelerates the ubiquitination and degradation of mad1 through the 26s proteasome pathway

SIGNOR-178586

Q9NQT8

Q7KZI7

0

phosphorylation

down-regulates activity

0.415

We report here the identification of GAKIN/KIF13B as a novel in vivo substrate for Par1b and present evidence that GAKIN/KIF13B plays a critical role in axon formation in neurons, which is negatively regulated by Par1b-mediated phosphorylation. Par1b phosphorylates GAKIN/KIF13B at both Ser1381 and Ser1410.

SIGNOR-262956

Q92769

P00519

0

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

P12004

Q14527

0

ubiquitination

up-regulates activity

0.78

HLTF promotes the Lys-63-linked polyubiquitination of proliferating cell nuclear antigen (PCNA) that is required for maintaining genomic stability.

SIGNOR-278608

P06493

Q8N884

1

phosphorylation

down-regulates activity

0.2

The major mitotic kinase CDK1-cyclin B complex phosphorylates human cGAS at S305 or mouse cGAS at S291, which inhibits its ability to synthesize cGAMP upon mitotic entry.

SIGNOR-276526

Q15722

P43250

0

phosphorylation

down-regulates activity

0.474

Thr(308) is a major residue involved in GRK6-mediated desensitization of BLT1 signaling.

SIGNOR-251213

Q9UHR4

P12931

0

phosphorylation

up-regulates activity

0.389

Here, we report that overexpression of IRTKS increases the speed of wound closure of HT1080 cells in a Src-dependent manner. Active Src phosphorylates IRTKS in vivo and in vitro. Deletion mapping and mutation analysis revealed that six tyrosine residues (Y37, Y156, Y163, Y274, Y293 and Y439) were Src-stimulated phosphorylation sites on IRTKS. Disruption of Src-stimulated IRTKS phosphorylation abolished the effect of IRTKS on wound closure. Collectively, these data suggest Src-stimulated IRTKS phosphorylation is essential for its function in cell motility.

SIGNOR-263041

Q12778

Q99576

0

relocalization

down-regulates activity

0.301

GILZ inhibits FOXO1, FOXO3, and FOXO4 transcriptional activities measured with natural or synthetic FOXO-responsive promoters in HL-60 cells.

SIGNOR-256146

Q96J92

P55017

1

phosphorylation

up-regulates activity

0.579

Threonine 48 was identified as the WNK4 phosphorylation site at mouse NCC|. Thus, WNK4 stimulates NCC in three ways: (1) direct phosphorylation and in turn increasing NCC protein abundance; (2) facilitating the phosphorylation of NCC by SPAK/OSR1 indirectly, and (3) phosphorylating and activating SPAK/OSR1.|Evidences from early studies using Xenopus oocytes and mammalian cells indicate that WNK4 inhibits NCC and PHAII-causing mutations relieve the inhibition

SIGNOR-264631

Q96TA1

P00533

0

phosphorylation

up-regulates activity

0.2

We demonstrate here that activated EGFR phosphorylates the Y593 residue of the protein known as family with sequence similarity 129, member B (FAM129B), which is overexpressed in many types of human cancer. FAM129B phosphorylation increased the interaction between FAM129B and Ras, resulting in reduced binding of p120-RasGAP to Ras.

SIGNOR-273637

O14733

P53779

1

phosphorylation

up-regulates

0.582

Two mapkks, sek1 and mkk7, synergistically activate jnk. Sek1 prefers the tyr-185 residue, and mkk7 prefers the thr-183 residue (17, 19).

SIGNOR-137609

Q9GZY8

O00429

1

relocalization

up-regulates activity

0.601

Mff functions as an essential factor in mitochondrial recruitment of Drp1.

SIGNOR-245957

P49715

Q16549

0

phosphorylation

down-regulates

0.2

Addition of active p38a induced phosphorylation of wild-type c/ebp_? (c/ebp_?WT) on serine 21

SIGNOR-186202

P46060

O75592

1

relocalization

down-regulates quantity by destabilization

0.315

SUMOylated RanGAP1 Inhibits MYCBP2 Activity and Mediates Its Transport to the Nucleus. Surprisingly, we did not find MYCBP2-dependent ubiquitylation of SUMOylated RanGAP1 but instead a strong inhibition of the ubiquitin ligase activity of MYCBP2 in the presence of SUMOylated RanGAP1, as determined by the presence of ubiquitylated proteins. this effect was specific for SUMOylated RanGAP1, because the unmodified form of RanGAP1 did not affect MYCBP2-dependent protein ubiquitylation. , SUMOylated RanGAP1 inhibited the ubiquitin ligase activity of MYCBP2, and it is tempting to speculate that SUMOylated RanGAP1 inhibits the ubiquitin ligase activity of MYCBP2 to ensure MYCBP2 silencing during its transport to the nucleus

SIGNOR-261203

O95747

Q13153

1

phosphorylation

down-regulates activity

0.382

OSR1 phosphorylated threonine 84 in the N-terminal regulatory domain of PAK1. phosphorylation of PAK1 by OSR1 desensitizes PAK1 to activation by small G proteins, providing a modulatory input to PAK1 activity.

SIGNOR-250210

Q96KB5

Q8TBB1

0

ubiquitination

down-regulates quantity by destabilization

0.375

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.

SIGNOR-272898

Q99986

Q9H4B4

0

phosphorylation

up-regulates

0.474

Vrk1 does not phosphorylate plk3, but plk3 phosphorylates the c-terminal region of vrk1 in ser342. Vrk1 with substitutions in s342 is catalytically active but blocks golgi fragmentation, indicating that its specific phosphorylation is necessary for this process.

SIGNOR-182858

P27361

P33076

1

phosphorylation

up-regulates

0.341

We found that in these cells, lipopolysaccharide stimulates the expression of mhc ii genes via the activation of erk1/2, which is mediated by toll-like receptor 4. Erk1/2 then phosphorylates the serine at position 357, which is located in a degron of ciita isoform 1 that leads to its monoubiquitylation.

SIGNOR-150545

Q8NFH5

P06493

0

phosphorylation

down-regulates activity

0.563

Collectively, these data show that mitotic hyperphosphorylation of Nup53 by CDK1 and PLK1 contributes to its removal from NPCs.|The combined mutation of the CDK1 and PLK1 sites to phosphomimetic residues almost completely abolished NPC integration of Nup53, indicating that hyperphosphorylation of Nup53 might be incompatible with its NPC association.

SIGNOR-278917

P16949

O96013

0

phosphorylation

down-regulates activity

0.283

Indeed, we show here that inactivating phosphorylation of the endogenous stathmin on serine-16 is also induced by the active PAK4 in mitotic egg extract and is likely to participate in the observed stabilization of the MT asters ( xref , right).

SIGNOR-280058

P31749

Q06187

1

phosphorylation

down-regulates quantity by destabilization

0.296

The activated serine/threonine kinase Akt/protein kinase B (PKB) phosphorylated Btk on two sites prior to 14-3-3ζ binding. The interaction sites were mapped to phosphoserine pS51 in the pleckstrin homology domain and phosphothreonine pT495 in the kinase domain.

SIGNOR-276466

Q13153

Q15746

1

phosphorylation

down-regulates activity

0.556

P21-activated kinase 1 (PAK1) phosphorylates MLCK, resulting in decreased MLCK activity.

SIGNOR-250317

P45983

P04150

1

phosphorylation

down-regulates

0.638

Taken together, these findings suggest that jnk-mediated phosphorylation of the gr-ser226 enhances gr nuclear export and may contribute to termination of gr-mediated transcription.

SIGNOR-93558

P08243

P08047

0

transcriptional regulation

up-regulates quantity by expression

0.2

Sp1 and Sp3 Activate Transcription Driven by the AS Promoter

SIGNOR-268019

P11362

O15530

1

phosphorylation

up-regulates activity

0.2

Y105 phosphorylation of PKM2, which is involved in FGFR1-regulated PDHK1 expression, appears to be an upstream event that precedes FGFR1-dependent phosphorylation and activation of PDHK1 in cancer cell metabolism.

SIGNOR-279174

P09874

P78527

0

phosphorylation

down-regulates activity

0.525

Therefore, through its interaction with Ku70/80 in the presence of dsDNA , DNA-PK phosphorylated PARP-1 at its catalytic CTD.

SIGNOR-280093

Q9BZL6

Q9GZY8

1

phosphorylation

up-regulates activity

0.2

The mitochondrial fission factor (MFF), the main mitochondrial receptor for the Dynamin-related protein 1 (DRP1), is directly phosphorylated by Protein Kinase D (PKD) specifically during mitosis. PKD-dependent MFF phosphorylation is required and sufficient for mitochondrial fission in mitotic but not in interphasic cells.|PKD directly phosphorylates MFF on serines 155, 172, and 275

SIGNOR-275947

Q03060

P06493

0

phosphorylation

down-regulates quantity by destabilization

0.296

The MAPKs extracellular signal-regulated kinases 1 and 2 physically interact with ICER and mediated the phosphorylation of ICER on a critical serine residue (Ser-41). A mutant form of ICER in which Ser-41 was substituted by alanine had a half-life 4-5 h longer than its wild-type counterpart. This alteration in stability was due to the inability of the Ser-41-mutant ICER to be efficiently ubiquitinated and degraded via the ubiquitin-proteasome pathway.

SIGNOR-275979

Q00535

P00519

0

phosphorylation

up-regulates activity

0.585

Phosphorylation of Cdk5 by c-Abl occurs on tyrosine 15 (Y15), which is stimulatory for p35/Cdk5 kinase activity.

SIGNOR-245288

P31749

O60343

1

phosphorylation

down-regulates

0.764

Recently, we identified a 160-kda protein in adipocytes, designated as160, that is phosphorylated by the insulin-activated kinase akt

SIGNOR-252594

Q15672

O14920

0

phosphorylation

down-regulates activity

0.332

Hence, our current study supports the pivotal role of beta-TRCP in IKKbeta mediated Twist degradation.|More importantly, IKK\u03b2-dependent phosphorylation of Twist at T125 and S127 governs its nuclear localization.

SIGNOR-278404

P15374

P62987

1

cleavage

up-regulates quantity

0.801

Here we provide data suggesting that two of the four mammalian ubiquitin precursors, UBA52 and UBA80, are processed mostly post-translationally whereas the other two, UBB and UBC, probably undergo a combination of co- and post-translational processing. Using an unbiased biochemical approach we found that UCHL3, USP9X, USP7, USP5 and Otulin/Gumby/FAM105b are by far the most active DUBs acting on these precursors.

SIGNOR-270827

P04637

P11166

1

transcriptional regulation

down-regulates quantity by repression

0.597

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-267464

Q05655

P67775

0

dephosphorylation

down-regulates activity

0.377

PP2A(c) displayed the highest specific activity towards PKCdelta. The role of PP2A(c) in the dephosphorylation of PKCdelta in cells was supported by the demonstration that these proteins could be co-immunoprecipitated from NIH3T3 cells.|In conclusion, the evidence here indicates that PKCdelta de-phosphorylation and hence inactivation is effected by PP2A with which it forms a complex

SIGNOR-248638

Q8N392

Q6P5Z2

0

phosphorylation

up-regulates activity

0.2

We present strong evidence that PKN3-ARHGAP18 interaction is increased upon ARHGAP18 phosphorylation and that the phosphorylation of ARHGAP18 by PKN3 enhances its GAP domain activity and contributes to negative regulation of active RhoA.|These results support our data from phosphoproteomic screen and suggest that ARHGAP18 can be phosphorylated by PKN3 on Thr154, Ser156 and Thr158.

SIGNOR-264572

Q07955

P49761

0

phosphorylation

up-regulates activity

0.531

In vitro, Clk/Sty efficiently phosphorylated the SR family member ASF/SF2 on serine residues located within its serine/arginine-rich region (the RS domain). Overexpression of the active Clk/Sty kinase caused a redistribution of SR proteins within the nucleus. These results suggest that Clk/Sty kinase directly regulates the activity and compartmentalization of SR splicing factors.

SIGNOR-273859

Q9Y297

P30304

1

ubiquitination

up-regulates

0.494

Scfb-trcp has recently been shown to degrade phosphorylated cdc25a in the s and g2 phases.

SIGNOR-128436

Q96GD4

P04637

1

phosphorylation

down-regulates

0.719

We show that aurora b phosphorylates p53 at s183, t211, and s215 to accelerate the degradation of p53 through the polyubiquitination-proteasome pathway, thus functionally suppressing the expression of p53 target genes involved in cell cycle inhibition and apoptosis (e.g., p21 and puma).

SIGNOR-197598

P30305

P45983

0

phosphorylation

down-regulates quantity by destabilization

0.284

Recently, we showed that Cdc25B is degraded rapidly by non-genotoxic stimuli that activate stress-responsive MAPKs, such as Jun N-terminal kinase (JNK) and p38 (Uchida et al., 2009). Our results suggested that these kinases phosphorylate specific Ser residues in the N-terminal region (S101 and S103) to induce Cdc25B degradation.Here, we report that Cdc25B was ubiquitylated by SCF(βTrCP) E3 ligase upon phosphorylation at two Ser residues in the βTrCP-binding-motif-like sequence D(94)AGLCMDSPSP(104).

SIGNOR-276352

Q13153

O14965

1

phosphorylation

up-regulates

0.417

The upstream pak1 kinase can phosphorylate aurora a at t288, autophosphorylation appears to be the essential mode of activation. Our experiments suggest that phosphorylation of t288 is important for regulation of the aurora2 kinase both for its activity and its stability

SIGNOR-205110

O95147

Q15750

1

dephosphorylation

down-regulates activity

0.298

DUSP14 directly interacted with TGF-beta-activated kinase 1 (TAK1)-binding protein 1 (TAB1) and dephosphorylated TAB1 at Ser (438), leading to TAB1 and TAK1 complex inactivation in T cells.

SIGNOR-277147

Q16543

P19784

0

phosphorylation

up-regulates activity

0.489

Phosphorylation of serine 13 is required for the proper function of the Hsp90 co-chaperone, Cdc37. | In this report, we demonstrate that mammalian Cdc37 is phosphorylated on Ser13 in situ in rabbit reticulocyte lysate and in cultured K562 cells and that casein kinase II is capable of quantitatively phosphorylating recombinant Cdc37 at this site.

SIGNOR-250982

P35568

P06213

0

phosphorylation

up-regulates activity

0.914

All known IRS proteins contain multiple YXXM motifs that upon phosphorylation by activated insulin receptors A previous study using phosphopeptides suggested that tyrosine-phosphorylated YXXM motifs at positions 608 and 939 in rat IRS-1 bind with high affinity to SH2 domains of p85, and motifs at positions 460 and 987 bind with lower affinity (10).

SIGNOR-235975

Q5FBB7

P0C0S8

0

relocalization

up-regulates activity

0.2

The complex between shugoshin and protein phosphatase 2A (Sgo1-PP2A) localizes to centromeres in mitosis, binds to cohesin in a reaction requiring Cdk-dependent phosphorylation of Sgo1, dephosphorylates cohesin-bound sororin, and protects a centromeric pool of cohesin from mitotic kinases and the cohesin inhibitor Wapl.|The centromeric localization of Sgo1 requires histone H2A phosphorylation at T120 (H2A-pT120) by the kinase Bub1.

SIGNOR-265262

P06493

Q8NHV4

1

phosphorylation

up-regulates activity

0.585

Here we report that the function of Nedd1 is regulated by Cdk1 and Plk1. During mitosis, Nedd1 is firstly phosphorylated at T550 by Cdk1, which creates a binding site for the polo-box domain of Plk1. Then, Nedd1 is further phosphorylated by Plk1 at four sites: T382, S397, S637 and S426. The sequential phosphorylation of Nedd1 by Cdk1 and Plk1 promotes its interaction with gamma-tubulin for targeting the gammaTuRC to the centrosome and is important for spindle formation.

SIGNOR-272973

P00519

P43351

1

phosphorylation

up-regulates activity

0.685

C-Abl tyrosine kinase associates with and phosphorylates Rad52 on tyrosine 104. he functional significance of c-Abl-dependent phosphorylation of Rad52 is underscored by our findings that cells that express the phosphorylation-resistant Rad52 mutant, in which tyrosine 104 is replaced by phenylalanine, exhibit compromised nuclear foci formation in response to IR.

SIGNOR-251435

P25098

P30559

1

phosphorylation

down-regulates activity

0.2

Recent experiments in COS-7 cells transfected with OTR have demonstrated that a rapid GRK2-mediated phosphorylation of the agonist-occupied OTR is a key first step leading to its desensitization, and that it precedes and is required for β-arrestin-dependent internalization

SIGNOR-270329

Q99683

P46734

1

phosphorylation

up-regulates activity

0.599

Ask1 is a member of a mapkkk family and functions as an upstream kinase engaged in c-jun nh2-terminal kinase (jnk)/p38 signaling via the phosphorylation and activation of mapkks, such as mkk3, -4, -6, and -7

SIGNOR-161763

P49910

O15105

1

transcriptional regulation

down-regulates quantity by repression

0.2

ZNF165 drives the unrestrained activation of transforming growth factor β (TGFβ) signalling by directly inactivating the expression of negative feedback pathway regulators, SMURF2, SMAD7 and PMEPA1.

SIGNOR-266093

P54829

P06241

1

dephosphorylation

down-regulates

0.527

Wild-type step(61) dephosphorylates fyn at tyr(420) but not at tyr(531). These results suggest that step regulates the activity of fyn by specifically dephosphorylating the regulatory tyr(420) and may be one mechanism by which fyn activity is decreased within psds.

SIGNOR-86791

P35228

P42224

0

transcriptional regulation

up-regulates quantity by expression

0.428

STAT1 binds as a homodimer to cis elements known as gammaactivated sequences in the promoters of the genes encoding NOS2, the MHC class II transactivator (CIITA) and IL-12, among others.

SIGNOR-249497

P04637

Q16539

0

phosphorylation

up-regulates activity

0.773

P38 regulates p53, but also in p53-defective tumor cells rewire their checkpoint response and become dependent in the p38/mk2 pathway in mcf-7 cells, p38 kinase activated p53 more effectively than other members of the ras pathway. p53 and p38 kinase exist in the same physical complex, and co-expression of p38 stabilized p53 protein. In vitro, p38 kinase phosphorylated p53 at ser33 and ser46, a newly identified site.

SIGNOR-155246

P53778

Q16875

1

phosphorylation

up-regulates quantity

0.2

KRAS transformation and overexpression of p38gamma increased expression of PFKFB3 and glucose transporter GLUT2

SIGNOR-279539

O60341

P17252

0

phosphorylation

up-regulates activity

0.352

Together, these data indicate that LPS-induced LSD1 phosphorylation by PKC\u03b1 is required for its interaction with p65 in the nucleus.|We have previously reported that LSD1 is phosphorylated by PKCalpha on serine 112 site, and knockin mice bearing phosphorylation defective Lsd1 SA/SA alleles show altered circadian rhythms and impaired phase resetting (Nam et al., 2014).

SIGNOR-279425