GleghornLab/Signor_2class · Datasets at Hugging Face

IdA string	IdB string	labels int64	mechanism string	effect string	score float64	sentence string	signor_id string
Q9NPD5	P42229	0	transcriptional regulation	up-regulates quantity by expression	0.2	PRL enhanced the binding of Stat5a to the OATP1B3 promoter and DNA-protein binding was inhibited in competition assays by excess OATP1B3 and Stat5 consensus oligomers but not by mutant Stat5 oligomers.\|PRL and GH induction of Oatp1b2 and OATP1B3 promoter activity required cotransfection of Stat5a and PRLRL or GHR.	SIGNOR-268990
Q969V4	Q92949	0	transcriptional regulation	up-regulates quantity by expression	0.364	FOXJ1 expression in basal cells induced the expression of a panel of cilia-associated genes, including centrin 2 (CETN2); dynein, axonemal, heavy chain 11 (DNAH11); dynein, axonemal, intermediate chain 1 (DNAI1); dynein, axonemal, light intermediate chain 1 (DNALI1); EF-hand domain, C-terminal, containing 1 (EFHC1); sperm associated antigen 6 (SPAG6); tektin 1 (TEKT1), TEKT2 and tubulin, alpha 1a (TUBA1A; Figure 3C and Additional file 2: Table S1).	SIGNOR-266936
O14965	P00352	1	phosphorylation	up-regulates activity	0.372	AURKA phosphorylates ALDH1A1 at three critical residues which exert a multifaceted regulation over its level, enzymatic activity, and quaternary structure. While all three phosphorylation sites contribute to its increased stability, T267 phosphorylation primarily regulates ALDH1A1 activity. AURKA-mediated phosphorylation rapidly dissociates tetrameric ALDH1A1 into a highly active monomeric species.	SIGNOR-276748
P04626	P17612	0	phosphorylation	up-regulates	0.405	Pka directly phosphorylated erbb2 on thr-686, a highly conserved intracellular regulatory site that was required for the pka-mediated synergistic enhancement of neuregulin-induced erbb2-erbb3 activation and proliferation in scs.	SIGNOR-181191
O14965	Q49MG5	1	phosphorylation	up-regulates	0.326	Asap is a novel substrate of the oncogenic mitotic kinase aurora-a: phosphorylation on ser625 is essential to spindle formation and mitosis.	SIGNOR-158210
P68400	Q9UNN5	1	phosphorylation	down-regulates activity	0.326	We previously identified the Fas-associated factor FAF1 as an in vitro substrate of protein kinase CK2 and determined Ser289 and Ser291 as phosphorylation sites.\|Therefore we assume that CK2‐mediated FAF1 phosphorylation influences the nuclear localization of FAF1 \| it implies that the major function of FAF1 might not be in the cytoplasm as an interacting partner of Fas.	SIGNOR-250864
O15350	Q9H4B4	0	phosphorylation	down-regulates activity	0.41	In this study, we found that Plk3 inhibits pro-apoptotic activity of p73 through physical interaction and phosphorylation.\|Plk3 inhibits pro-apoptotic activity of p73 through physical interaction and phosphorylation.	SIGNOR-279647
P27986	Q9H0K1	0	phosphorylation	up-regulates activity	0.322	The Regulatory Subunit of PI3K Is a Direct Catalytic Target of SIK2. These data confirm that p85α is a direct catalytic substrate of SIK2 and that SIK2 S154 phosphorylation significantly increases the activity of the PI3K/AKT pathway in ovarian cancer cells.	SIGNOR-277269
Q13363	P31749	0	phosphorylation	down-regulates quantity	0.483	Co-expression of Pc2 and Akt1 results in both phosphorylation and ubiquitylation of CtBP1, thereby targeting CtBP1 for degradation.\|CtBP1 phosphorylation by Akt1 appears to both decrease dimerization and induce ubiquitylation.	SIGNOR-278304
P53355	P04637	1	phosphorylation	up-regulates	0.558	Dna damage-activated protein kinases like chk1/2 modify the box-i domain of p53 at thr18 and ser20 (46) by an allosteric mechanism (10).	SIGNOR-153491
O95644	Q13627	0	phosphorylation	up-regulates activity	0.429	DYRK1A phosphorylation of NFATc1 and alphaA at S261, S278, S403 and S409 interfered with NFATc1 ubiquitination and ubiquitin-proteasome degradation.\|Here, we demonstrated that DYRK1A increased NFATc1 (NFATc1 and alphaA isoform) protein stability, in contrast to the decrease of NFATc2 protein stability by DYRK1A.	SIGNOR-278278
P45983	P49023	1	phosphorylation	up-regulates activity	0.676	JNK1 phosphorylates serine 178 on paxillin, a focal adhesion adaptor, both in vitro and in intact cells. NBT-II cells expressing the Ser 178 --> Ala mutant of paxillin (Pax(S178A)) formed focal adhesions and exhibited the limited movement associated with such contacts in both single-cell-migration and wound-healing assays. In contrast, cells expressing wild-type paxillin moved rapidly and retained close contacts as the predominant adhesion.	SIGNOR-250129
P28482	Q9H9Z2	1	phosphorylation	down-regulates activity	0.262	Here we show that Lin28a is directly phosphorylated by ERK1/2 kinases at Ser-200.	SIGNOR-277338
P04637	Q68DV7	0	ubiquitination	down-regulates quantity by destabilization	0.451	Moreover, RNF43 polyubiquitinates p53 which further leads to its destabilization resulting in a decrease in induction of the p53 apoptotic pathway, a hitherto unknown process targeted by NP for p53 stabilization and accumulation.	SIGNOR-278714
Q01094	Q13315	0	phosphorylation	up-regulates quantity by stabilization	0.679	Selective induction of e2f1 in response to dna damage, mediated by atm-dependent phosphorylation. We identify a site for atm/atr phosphorylation in the amino terminus of e2f1 and we show that this site is required for atm-mediated stabilization of e2f1. Finally, we also show that e2f1 is required for dna damaged induced apoptosis in mouse thymocytes.	SIGNOR-109416
Q9Y6I3	P00533	1	relocalization	down-regulates	0.596	Epsin 1 is involved in recruitment of ubiquitinated egf receptors into clathrin-coated pits this supports the contention that epsin 1 promotes endocytosis of the ubiquitinated egfr.	SIGNOR-182562
P17612	Q14978	1	phosphorylation	up-regulates	0.307	Here we demonstrate that protein kinase a (pka)-dependent phosphorylation of nopp140 at ser 627, together with c/ebpbeta, induces agp gene expression synergistically.	SIGNOR-91186
P51452	P43405	0	phosphorylation	up-regulates activity	0.363	ZAP-70 and Syk also tyrosine-phosphorylated VHR in COS-1 cells (Fig. 2d), whereas other kinases (Csk, Lck, Fyn, Jak2, Bcr-Abl and Itk) had little effect. Finally, recombinant ZAP-70 readily phosphorylated VHR in vitro (Fig. 2f).	SIGNOR-275999
Q6PJ69	Q9NRY4	1	polyubiquitination	down-regulates quantity by destabilization	0.2	Ubiquitin ligase TRIM65 promotes colorectal cancer metastasis by targeting ARHGAP35 for protein degradation	SIGNOR-272256
Q00987	O94992	1	ubiquitination	up-regulates activity	0.465	Here we report that human double minute-2 protein (HDM2), a p53-specific E3 ubiquitin ligase, specifically ubiquitinates HEXIM1 through the lysine residues located within the basic region of HEXIM1.\|However, the HDM2-induced HEXIM1 ubiquitination does not lead to proteasome-mediated protein degradation.	SIGNOR-278701
Q9UK32	Q09472	1	phosphorylation	down-regulates activity	0.253	Figure 2G shows that Ser89 phosphorylation of p300, an event that inhibits p300’s acetyltransferase activity (13), was decreased in RSK4-silenced A549 and T24 cells. Consequently, RSK4 may regulate the activity of the NFκB pathway by direct phosphorylation of p300, as recombinant RSK4 phosphorylates p300 on Ser89 in vitro	SIGNOR-275796
O43561	Q13043	0	phosphorylation	up-regulates activity	0.2	MST kinase phosphorylates and activates LATS kinase.	SIGNOR-279661
P19174	P04629	0	phosphorylation	up-regulates	0.652	The nerve growth factor (ngf) receptor/trk associated with and phosphorylated phospholipase c gamma (plc gamma)	SIGNOR-38538
P08670	P53350	0	phosphorylation	up-regulates	0.2	We observed that plk1 phosphorylates vimentin on ser82, which in turn regulates cell surface levels of 1 integrin.	SIGNOR-159386
P20701	O60674	0	phosphorylation	up-regulates activity	0.268	PTKs of the JAK and SRC families have a regulatory role in LFA-1 affinity triggering, with JAKs showing a positive role (3), whereas SRCs possibly have a negative role.	SIGNOR-254739
P21754	Q5JUK2	0	transcriptional regulation	up-regulates quantity by expression	0.378	Cotransfection of a mouse Sohlh1 expression vector with E box-containing promoter regions of mouse Lhx8, Zp1, and Zp3 fused to luciferase resulted in significant transactivation . Mutation of the E box sequences abolished SOHLH1-dependent stimulation. Thus, Lhx8, Zp1, and Zp3 are likely direct downstream target genes of SOHLH1 through the E box elements in their promoters.	SIGNOR-266078
P62136	Q70Z35	1	dephosphorylation	up-regulates activity	0.2	PREX2 is dephosphorylated by PP1α and PP2A.PAK-mediated phosphorylation of PREX2 reduced GEF activity toward Rac1 by inhibiting PREX2 binding to PIP3 and Gβγ.	SIGNOR-277183
Q86YD1	Q96BR1	0	phosphorylation	down-regulates quantity by destabilization	0.2	In this study, we find that the understudied serum and glucocorticoid-induced kinase-2 (SGK2) phosphorylates PTOV1 at S36.	SIGNOR-279283
Q13315	P17096	1	phosphorylation	up-regulates activity	0.2	21 As shown in Fig. 2 b, ATM was able to phosphorylate in vitro the C-terminal peptide of HMGA1.	SIGNOR-279493
Q8IUQ4	P49757	1	ubiquitination	down-regulates	0.4	We report that siah-1 interacts directly with and promotes the degradation of the cell fate regulator numb.	SIGNOR-113469
O95714	Q96JN8	1	polyubiquitination	down-regulates quantity by destabilization	0.456	NEURL4 is a substrate of HERC2, and together these results indicate that the NEURL4-HERC2 complex participates in the ubiquitin-dependent regulation of centrosome architecture.	SIGNOR-272921
P35790	Q00987	1	phosphorylation	down-regulates quantity by destabilization	0.274	The data presented here provides evidence for a molecular mechanism by which CKI-dependent phosphorylation of Mdm2 at multiple sites triggers SCF \u03b2-TRCP -mediated Mdm2 destruction ( xref ).	SIGNOR-279606
Q00653	O15111	0	phosphorylation	up-regulates activity	0.791	Ikkalfa phosphorylates p100, leading to its proteasomal processing to p52.	SIGNOR-124230
P15172	Q14469	0	transcriptional regulation	down-regulates activity	0.294	Notch signaling up-regulated HES1 mRNA expression within 1 h and subsequently reduced expression of MyoD mRNA	SIGNOR-243181
O95863	Q9NRM7	0	phosphorylation	up-regulates	0.528	Lats2 kinase potentiates snail1 activity by promoting nuclear retention upon phosphorylation. during tgf_-induced emt lats2 is activated and snail1 phosphorylated at t203.	SIGNOR-176647
P06493	P33991	1	phosphorylation	down-regulates activity	0.592	We report here that human mcm4, a subunit of the putative dna replicative helicase, is extensively phosphorylated in hela cells when they are incubated in the presence of inhibitors of dna synthesis or are exposed to uv irradiation. The data presented here indicate that the consecutive actions of atr-chk1 and cdk2 kinases are involved in this phosphorylation in the presence of hydroxyurea. Phosphorylation of t19 correlates with lowered level of dna helicase activity of the purified mcm4,6,7 complex.	SIGNOR-100877
Q8IXH7	P12931	0	phosphorylation	down-regulates activity	0.336	Here we show that c-Src interacts with TH1 by GST-pull down assay, coimmunoprecipitation and confocal microscopy assay. The interaction leads to phosphorylation of TH1 at Tyr-6 in vivo and in vitro. Phosphorylation of TH1 decreases its association with A-Raf and PAK1.	SIGNOR-276402
P49841	P25054	1	phosphorylation	up-regulates	0.758	Gsk-3beta-dependent phosphorylation of apc.	SIGNOR-75366
P50553	Q9HCK8	0	transcriptional regulation	down-regulates quantity	0.2	Many of the most significantly up-regulated genes in Chd8+/− and Chd8−/− NPCs are involved in later stages of neuronal development, including Ascl1 [a central driver of neural reprogramming (29)], Dcx, Map2, Nefm, Neurod4, and Neurog1 (Fig. 2 E and F). Additionally, we found that Sox3 is derepressed in both Chd8+/− and Chd8−/− NPCs, and several other Sox TF members (Sox2, Sox7, and Sox11) became derepressed in the Chd8−/− cells	SIGNOR-268914
P01106	P30304	1	transcriptional regulation	up-regulates quantity by expression	0.627	Expression of Cdc25A is transcriptionally regulated by Myc and E2F-1 , both of which are expressed in MCF-7 cells in response to estrogen	SIGNOR-245465
P07814	Q00535	0	phosphorylation	down-regulates	0.2	Ser(886) phosphorylation is required for the interaction of nsap1, which blocks eprs binding to target mrnas. The same phosphorylation event induces subsequent binding of ribosomal protein l13a and gapdh and restores mrna binding. Ifn-_ activates cdk5 to phosphorylate ser(886) in the linker domain of glutamyl-prolyl trna synthetase (eprs), the initial event in assembly of the gait complex. Cdk5/p35 also induces, albeit indirectly via a distinct kinase, phosphorylation of ser(999), the second essential event in gait pathway activation	SIGNOR-187383
Q9UQM7	Q05682	1	phosphorylation	down-regulates	0.2	Smooth muscle caldesmon was phosphorylated by smooth muscle calmodulin-dependent protein kinase. Ii	SIGNOR-22635
Q15910	Q9P275	0	deubiquitination	up-regulates quantity by stabilization	0.2	We observed a MELK-mediated increase of EZH2 S220 phosphorylation along with a concomitant loss of EZH2 K222 ubiquitination, suggesting a phosphorylation-dependent regulation of EZH2 ubiquitination. Furthermore, we identify USP36 as the deubiquitinating enzyme that deubiquitinates EZH2 at K222.	SIGNOR-277481
P46531	P49336	0	phosphorylation	down-regulates	0.552	Purified recombinant cycc:cdk8 phosphorylates the notch icd within the tad and pest domains, and expression of cycc:cdk8 strongly enhances notch icd hyperphosphorylation and pest-dependent degradation by the fbw7/sel10 ubiquitin ligase in vivo.	SIGNOR-130640
O14757	P30305	1	phosphorylation	down-regulates activity	0.785	Here, we show that cdc25b is phosphorylated by chk1 in vitro on multiple residues, including s230 and s563.We show that the s230-phosphorylated form of cdc25b is located at the centrosome from early s phase until mitosis. Furthermore, mutation of s230 to alanine increases the mitotic-inducing activity of cdc25b	SIGNOR-149898
Q9NSC5	Q9UQM7	0	phosphorylation	down-regulates activity	0.2	Homer3 is phosphorylated at Ser120, Ser159, and Ser176 by CaMKII in vitro. Homer3 phosphorylation reduces its affinity for target molecules and modulates the Ca2+ signaling patterns induced by mGluR1α activation	SIGNOR-262685
Q9Y4K3	Q9BQ95	1	ubiquitination	down-regulates activity	0.79	Here we demonstrate that engagement of a subset of Toll-like receptors (TLR1, TLR2 and TLR4) results in the recruitment of mitochondria to macrophage phagosomes and augments mROS production. This response involves translocation of a TLR signalling adaptor, tumour necrosis factor receptor-associated factor 6 (TRAF6), to mitochondria, where it engages the protein ECSIT (evolutionarily conserved signalling intermediate in Toll pathways), which is implicated in mitochondrial respiratory chain assembly. Interaction with TRAF6 leads to ECSIT ubiquitination and enrichment at the mitochondrial periphery, resulting in increased mitochondrial and cellular ROS generation	SIGNOR-260370
Q96FI4	Q12899	0	ubiquitination	down-regulates quantity	0.247	Mule and TRIM26 ubiquitylate NEIL1 in vitro within C-terminal lysine residues.\|Similar to these previous results, we again demonstrate that a knockdown of Mule or TRIM26 causes an elevation in the protein stability of NEIL1 in comparison to non-targeting siRNA, unirradiated control (Figure and ; compare lanes 1 and 2).	SIGNOR-278647
P51784	P68104	1	deubiquitination	up-regulates activity	0.2	USP11 interacted with and deubiquitinated eEF1A1 on Lys439, thereby inhibiting its ubiquitin-mediated degradation. Subsequently, the elevated expression of eEF1A1 resulted in its binding to SP1, which in turn drove the binding of SP1 to its target HGF gene promoter to increase its transcription	SIGNOR-278107
O14920	P23396	1	phosphorylation	up-regulates activity	0.332	IKKbeta overexpression activated NF-kappaB measured by luciferase assays , and also induced the nuclear translocation of wild-type, but not S209A, RPS3 (XREF_FIG).\|Therefore, RPS3 S209 phosphorylation by IKK\u03b2 is apparently required for RPS3 in directing NF-\u03baB to a specific subset of target genes.	SIGNOR-278360
P49336	P42224	1	phosphorylation	up-regulates activity	0.392	We previously demonstrated that Mediator kinase inhibitor cortistatin A (CA) reduced proliferation of JAK2-mutant AML in vitro and in vivo and also suppressed CDK8-dependent phosphorylation of STAT1 at serine 727. Here we report that phosphorylation of STAT1 S727 promotes the proliferation of AML cells with JAK-STAT pathway activation.	SIGNOR-273179
Q9NR28	O15033	0	ubiquitination	down-regulates quantity by destabilization	0.377	AREL1 ubiquitinated SMAC, primarily on Lys62 and Lys191 \|E701A substitution in the AREL1 HECT domain substantially increased its autopolyubiquitination and SMAC ubiquitination activity, whereas deletion of the last three amino acids at the C terminus completely abrogated AREL1 autoubiquitination and reduced SMAC ubiquitination.	SIGNOR-267672
P17252	P48730	1	phosphorylation	up-regulates activity	0.2	In the present study we analyzed the CK1δ kinase domain for phosphorylation sites targeted by PKCα. Several phosphorylation sites were identified in vitro by initially using GST-CK1δ wild type and phosphorylation-site mutant protein fragments originating from the CK1δ kinase domain. Residues S53, T176, and S181 could finally be confirmed as targets for PKCα. Determination of kinetic parameters of full-length wild type and mutant GST-CK1δ-mediated substrate phosphorylation revealed that integrity of residue T176 is crucial for maintaining CK1δ kinase activity.	SIGNOR-277452
P68400	Q9UD71	1	phosphorylation	up-regulates activity	0.34	Study of [Plphosphate release during manual Edman degradation confirmed that the phosphorylated residues in rat DARPP-32 were Ser45 and Ser102. \| Phosphorylation by casein kinase II did not affect the potency of DARPP-32 as an inhibitor of protein phosphatase-1, which depended only on phosphorylation of Thr34 by cAMP-dependent protein kinase. However, phosphorylation of DARPP-32 by casein kinase II facilitated phosphorylation of Thr34 by cAMP-dependent protein kinase	SIGNOR-250927
P68431	Q92831	0	acetylation	down-regulates activity	0.2	The HAT module within the SAGA and ADA complexes acetylates histone H3, mainly on residues K9 and K14.	SIGNOR-269611
Q16695	Q9C0A6	0	methylation	up-regulates activity	0.2	SETD5 Exhibits Intrinsic Methyltransferase Activity on H3K36. This assay showed that SETD5 has specific histone methyltransferase activity toward K36 but not for other residues such as K4 and K27 (Figure 8B). we revealed that SETD5 is endowed with H3K36 methyltransferase, which is necessary for RNA elongation and processing and, ultimately, correct gene transcription.	SIGNOR-264621
O95476	Q14693	1	dephosphorylation	up-regulates activity	0.78	Dullard significantly dephosphorylates mouse lipin 1b only in BHK cells (Fig. 5A). This is most clearly seen by using the antibody prepared against the phosphorylation site Ser-106.\|Dephosphorylation of lipin results in its translocation to the nuclear envelope and endoplasmic reticulum membranes from the cytosol and generation of diacylglycerol	SIGNOR-248346
Q04759	Q9Y4G8	1	phosphorylation	up-regulates	0.2	After t-cell activation, the direct phosphorylation of rapgef2 at ser960 by pkc- theta regulates rap1 activation as well as lfa-1 adhesiveness to icam-1. Pkc- theta and its effector rapgef2 are critical factors in tcr signaling to rap1	SIGNOR-181186
Q04759	Q8IV61	1	phosphorylation	up-regulates	0.328	Activation of rasgrp3 by phosphorylation of thr-133 is required for b cell receptor-mediated ras activation. our data suggest that pkc, after being activated by diacylglycerol, phosphorylates rasgrp3, thereby contributing to its full activation.	SIGNOR-130490
P46531	Q13627	0	phosphorylation	down-regulates	0.396	Dyrk1a physically interacts with the nicd inducing its phosphorylation in the ankyrin domain, thereby attenuating notch .	SIGNOR-185494
P35968	P62993	1	relocalization	up-regulates activity	0.686	In a similar fashion, KDR associates with Grb2 and Nck in a ligand-dependent fashion, suggesting Shc, Grb2, and Nck as potential candidates involved in the regulation of endothelial function.	SIGNOR-261948
P46020	P17612	0	phosphorylation	up-regulates activity	0.432	Phosphorylation of the alpha and beta subunits by the 3',5'-cyclic adenosine monophosphate (cAMP)-dependent protein kinase (PKA) also relieves inhibition of the gamma subunit and thereby activates the enzyme.	SIGNOR-267411
P05412	P68400	0	phosphorylation	down-regulates	0.592	Casein kinase ii is a negative regulator of c-jun dna binding and ap-1 activitywe show that two of these sites, thr-231 and ser-249, are phosphorylated by casein kinase ii (ckii).	SIGNOR-19607
Q6ZVD8	P23443	1	dephosphorylation	down-regulates activity	0.49	We show that PHLPP preferentially dephosphorylates the hydrophobic motif T389 site in S6K1 in vitro	SIGNOR-248247
P21802	P62993	1	phosphorylation	up-regulates	0.773	Inhibition of basal fgf receptor signaling by dimeric grb2.	SIGNOR-197980
P53355	P98161	1	phosphorylation	up-regulates activity	0.2	In addition, the tumor suppressor death-associated protein kinase phosphorylates and activates PKD1 in response to oxidative damage ( xref ).	SIGNOR-279985
Q8IVM0	P00533	0	phosphorylation	down-regulates activity	0.415	We also detected tyrosine phosphorylation of Ymer by EGF stimulation as previously reported (Fig. 1A). Furthermore, we verified that EGF receptor-mediated tyrosine phosphorylation of Ymer is inhibited by AG1478, which is known as an EGF receptor tyrosine kinase inhibitor (Fig. 1B). A luciferase reporter assay showed that mutation of tyrosines on Ymer (YmerY217/279/304F) results in loss of the inhibitory activity for NF-kappaB signaling.	SIGNOR-262851
Q05639	P45983	0	phosphorylation	down-regulates quantity by destabilization	0.374	Ribosome-associated JNK phosphorylates the eukaryotic translation elongation factor 1A isoform 2 (eEF1A2) on serines 205 and 358 to promote degradation of NSPs by the proteasome.	SIGNOR-276492
Q9HAT8	Q96P20	1	ubiquitination	up-regulates activity	0.2	Pellino2 promotes ubiquitination of NLRP3.\|We now demonstrate that Pellino2 can promote increased production of mature bioactive IL-1beta by facilitating activation of the NLRP3 inflammasome.	SIGNOR-278525
P25116	P00747	0	cleavage	down-regulates activity	0.624	Plasmin mediates the lysis of fibrin clots and could in different studies activate platelets or inhibit the responses induced by thrombin (41-43). Our study favors a net inactivating effect on PAR1 despite minor cleavage at Arg41, on the basis of preferential cleavage at positions Arg70 and Lys76, COOH-terminal to the Arg41-Ser42 activation site.	SIGNOR-263572
Q16611	Q9NR28	1	relocalization	up-regulates	0.522	Bax and/or bak-mediated release of pro-apoptotic mediators including smac/diablo and omi	SIGNOR-118905
P46934	Q9Y4G8	1	ubiquitination	down-regulates quantity	0.401	In line with the previous result (XREF_FIG), overexpression of NEDD4-1 reduced the level of CNrasGEF significantly (XREF_FIG).\|NEDD4-1 ubiquitinates CNrasGEF in glioma cells.	SIGNOR-278705
Q12800	P28482	0	phosphorylation	down-regulates	0.335	We previously established that phosphorylation of lsf in early g1 at ser-291 and ser-309 inhibits its transcriptional activity and that dephosphorylation later in g1 is required for its reactivation. At the peak activities of erk and cyclin c/cdk2 in early g1, lsf is efficiently phosphorylated on ser-291 and ser-309.	SIGNOR-184168
P49327	P19474	0	ubiquitination	down-regulates quantity by destabilization	0.2	FASN acetylation enhanced its association with the E3 ubiquitin ligase TRIM21. Acetylation destabilized FASN and resulted in decreased de novo lipogenesis and tumor cell growth. FASN acetylation was frequently reduced in human hepatocellular carcinoma samples, which correlated with increased HDAC3 expression and FASN protein levels.	SIGNOR-267368
Q13163	P10912	0	phosphorylation	up-regulates activity	0.2	The MEK5-dependent activation of ERK5 promotes binding of the transcription factor SP1 to the promoter of the genes encoding the transcription factors Klf2 and Klf4, leading to their increased abundance. Subsequently, Klf2 and Klf4 bind to the Npnt promoter and induce the production of nephronectin during myoblast fusion	SIGNOR-255452
Q13459	P61586	1	gtpase-activating protein	down-regulates activity	0.774	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-260509
P41208	Q92949	0	transcriptional regulation	up-regulates quantity by expression	0.353	FOXJ1 expression in basal cells induced the expression of a panel of cilia-associated genes, including centrin 2 (CETN2); dynein, axonemal, heavy chain 11 (DNAH11); dynein, axonemal, intermediate chain 1 (DNAI1); dynein, axonemal, light intermediate chain 1 (DNALI1); EF-hand domain, C-terminal, containing 1 (EFHC1); sperm associated antigen 6 (SPAG6); tektin 1 (TEKT1), TEKT2 and tubulin, alpha 1a (TUBA1A; Figure 3C and Additional file 2: Table S1).	SIGNOR-266930
Q9NS23	Q13315	0	phosphorylation	up-regulates	0.549	We show that, upon dna damage, rassf1a is phosphorylated by atm on ser131 and is involved in the activation of both mst2 and lats1, leading to the stabilization of p73.	SIGNOR-161934
Q13315	P06748	1	phosphorylation	up-regulates activity	0.352	In addition to Serine 125, ATM may also phosphorylate other sites on NPM.	SIGNOR-280182
Q13153	P53667	1	phosphorylation	up-regulates activity	0.614	Activation of lim-kinase by pak1 couplesp21-activated kinase (pak1) phosphorylates lim-kinase at threonine residue 508 within lim-kinase's activation loop	SIGNOR-72142
P49327	Q5VWC8	0	chemical activation	up-regulates activity	0.2	Very long-chain fatty acids are produced through a four-step cycle. However, the 3-hydroxyacyl-CoA dehydratase catalyzing the third step in mammals has remained unidentified. Mammals have four candidates, HACD1-4, based on sequence similarities to the recently identified yeast Phs1, although HACD3 and HACD4 share relatively weak similarity. We demonstrate that all four of these human proteins are indeed 3-hydroxyacyl-CoA dehydratases,	SIGNOR-267763
Q13627	P53805	1	phosphorylation	up-regulates	0.562	In the present study, dyrk1a is shown to directly interact with and phosphorylate rcan1 at ser112 and thr192 residues. Dyrk1a-mediated phosphorylation of rcan1 at ser112 primes the protein for the gsk3_-mediated phosphorylation of ser108.	SIGNOR-102290
P46940	P17252	0	phosphorylation	up-regulates	0.258	Using a mass spectrometry-based assay, we show that egf induces phosphorylation of iqgap1 ser(1443), a residue known to be phosphorylated by pkcthe nonphosphorylatable iqgap1 s1441a/s1443a had no effect. In contrast, the s1441e/s1443d mutation markedly enhanced the ability of iqgap1 to induce neurite outgrowth.	SIGNOR-128714
Q05516	P24941	0	phosphorylation	down-regulates	0.282	Here we show that the main cyclin-dependent kinase involved at the g(1) to s transition (cdk2) phosphorylates plzf at two consensus sites found within pest domains present in the hinge region of the protein. This phosphorylation triggers the ubiquitination and subsequent degradation of plzf, which impairs plzf transcriptional repression ability and antagonizes its growth inhibitory effects.	SIGNOR-160630
Q00535	Q8N5V2	1	phosphorylation	up-regulates activity	0.42	Importantly, ephexin1, a Rho GEF, is phosphorylated by Cdk5 in vivo .	SIGNOR-279021
P15336	Q9H4B4	0	phosphorylation	up-regulates	0.2	Phosphorylation of thr-69 by mapk14 and mapk11, and at thr-71 by mapk1/erk2, mapk3/erk1, mapk11, mapk12 and mapk14 in response to external stimulus like insulin causes increased transcriptional activity.	SIGNOR-163274
P17612	Q2Q1W2	1	phosphorylation	up-regulates quantity by stabilization	0.2	These observations suggested that LINK-A expression potentially inhibits PKA phosphorylation/activity and PKA-mediated phosphorylation of TRIM71 at Ser3.	SIGNOR-277454
P12931	Q9H7P9	1	phosphorylation	up-regulates activity	0.2	Through deletion and base substitution mutagenesis we have identified Tyr489 of PLEKHG2 as the site phosphorylated by cSrc.The interaction between PLEKHG2 and the full-length of PIK3R3, but not ABL1, occurs in a tyrosine-phosphorylation-dependent manner.	SIGNOR-273808
Q14289	P29474	1	phosphorylation	down-regulates	0.309	We found that fluid shear stress induces the association of enos with the proline-rich tyrosine kinase 2 (pyk2) in endothelial cells and that the enos immunoprecipitated from enos- and pyk2-overexpressing hek293 cells was tyrosine-phosphorylated on tyr657.	SIGNOR-161824
P15498	P00519	0	phosphorylation	up-regulates	0.401	Thus, the c-terminal tail of vav serves as a direct substrate of bcr-abl in vitro.	SIGNOR-114091
Q05655	P23396	1	phosphorylation	up-regulates activity	0.2	Here we show that PKCδ phosphorylates rpS3 resulting in its mobilization in the nucleus to repair damaged DNA	SIGNOR-260895
Q9HB09	P49841	0	phosphorylation	up-regulates	0.338	Gsk3b phosphorylates bcl2l12 at s156. Ectopic expression of gfp-fused bcl2l12 or bcl2l12a in u87mg cells leads to repression of apoptotic markers and protects against staurosporine (sts) insults, indicating an antiapoptotic role for both bcl2l12 and bcl2l12a. In contrast, no anti-apoptotic ability was seen in bcl2l12(s156a)	SIGNOR-195512
P53778	P04637	1	phosphorylation	up-regulates activity	0.474	Furthermore, upon activation by oncogenic ras, p38gamma stimulated the transcriptional activity of p53 by phosphorylating p53 at Ser(33), suggesting that the ability of p38gamma to mediate senescence is at least partly achieved through p53.	SIGNOR-280026
Q9H4B4	P16104	1	phosphorylation	up-regulates activity	0.2	Phosphorylation of H2AX at serine 139 was catalyzed by hyperosmotic stress-induced activation of Plk3.\|Osmotic stress induced phosphorylation of H2AX by polo like kinase 3 affects cell cycle progression in human corneal epithelial cells.\|Our results for the first time reveal that hyperosmotic stress-activated Plk3 elicited \u03b3H2AX.	SIGNOR-280073
P13807	P17612	0	phosphorylation	down-regulates activity	0.508	The results presented in this paper show that the phosphorylation of glycogen synthetase a by cyclic AMP-dependent protein kinase results in the phosphorylation of two distinct serines termed site-l and site-2, which account for 90% of the total phosphorylation	SIGNOR-253009
P16591	Q05397	1	phosphorylation	up-regulates activity	0.251	The Fer mediated phosphorylation of specific tyrosine residues of FAK was abolished by cotransfection of shRNA against Fer (i.e., shFer), but not by control shRNA, indicating that the phosphorylation of Tyr577, 861, or 925 of FAK in suspended cells was indeed caused by Fer.	SIGNOR-279409
Q15811	P60953	1	guanine nucleotide exchange factor	up-regulates activity	0.848	Significantly, here we identify the long isoform of ITSN-1, which has Cdc42 GEF activity\| We propose that GCC88 recruits ITSN-1-L to the TGN, which in turn activates Cdc42 at the trans-face of the Golgi (Figure 9A).	SIGNOR-260612
P35790	Q14693	1	phosphorylation	down-regulates activity	0.273	Because CKI is a constitutively active kinase and ubiquitously distributed in many cell types, high mTORC1 activity depending on nutritional status may be a physiological cue for Lipin1 degradation mediated by CKI and beta-TRCP.\|Thus, we propose that mTORC1 may function as a priming kinase for CKI to promote the phosphorylation of the degron motif in Lipin1.	SIGNOR-280228
Q13794	P30679	1	phosphorylation	up-regulates activity	0.2	Ga16 is phosphorylated in vivo by PMA and by TRH receptor stimulation	SIGNOR-278131
Q7L7X3	P46734	1	phosphorylation	up-regulates activity	0.578	The activation of and binding to MEK3 by TAO1 implicates TAO1 in the regulation of the p38-containing stress-responsive MAP kinase pathway	SIGNOR-60818

Q9NPD5

P42229

0

transcriptional regulation

up-regulates quantity by expression

0.2

PRL enhanced the binding of Stat5a to the OATP1B3 promoter and DNA-protein binding was inhibited in competition assays by excess OATP1B3 and Stat5 consensus oligomers but not by mutant Stat5 oligomers.|PRL and GH induction of Oatp1b2 and OATP1B3 promoter activity required cotransfection of Stat5a and PRLRL or GHR.

SIGNOR-268990

Q969V4

Q92949

0

transcriptional regulation

up-regulates quantity by expression

0.364

FOXJ1 expression in basal cells induced the expression of a panel of cilia-associated genes, including centrin 2 (CETN2); dynein, axonemal, heavy chain 11 (DNAH11); dynein, axonemal, intermediate chain 1 (DNAI1); dynein, axonemal, light intermediate chain 1 (DNALI1); EF-hand domain, C-terminal, containing 1 (EFHC1); sperm associated antigen 6 (SPAG6); tektin 1 (TEKT1), TEKT2 and tubulin, alpha 1a (TUBA1A; Figure 3C and Additional file 2: Table S1).

SIGNOR-266936

O14965

P00352

1

phosphorylation

up-regulates activity

0.372

AURKA phosphorylates ALDH1A1 at three critical residues which exert a multifaceted regulation over its level, enzymatic activity, and quaternary structure. While all three phosphorylation sites contribute to its increased stability, T267 phosphorylation primarily regulates ALDH1A1 activity. AURKA-mediated phosphorylation rapidly dissociates tetrameric ALDH1A1 into a highly active monomeric species.

SIGNOR-276748

P04626

P17612

0

phosphorylation

up-regulates

0.405

Pka directly phosphorylated erbb2 on thr-686, a highly conserved intracellular regulatory site that was required for the pka-mediated synergistic enhancement of neuregulin-induced erbb2-erbb3 activation and proliferation in scs.

SIGNOR-181191

O14965

Q49MG5

1

phosphorylation

up-regulates

0.326

Asap is a novel substrate of the oncogenic mitotic kinase aurora-a: phosphorylation on ser625 is essential to spindle formation and mitosis.

SIGNOR-158210

P68400

Q9UNN5

1

phosphorylation

down-regulates activity

0.326

We previously identified the Fas-associated factor FAF1 as an in vitro substrate of protein kinase CK2 and determined Ser289 and Ser291 as phosphorylation sites.|Therefore we assume that CK2‐mediated FAF1 phosphorylation influences the nuclear localization of FAF1 | it implies that the major function of FAF1 might not be in the cytoplasm as an interacting partner of Fas.

SIGNOR-250864

O15350

Q9H4B4

0

phosphorylation

down-regulates activity

0.41

In this study, we found that Plk3 inhibits pro-apoptotic activity of p73 through physical interaction and phosphorylation.|Plk3 inhibits pro-apoptotic activity of p73 through physical interaction and phosphorylation.

SIGNOR-279647

P27986

Q9H0K1

0

phosphorylation

up-regulates activity

0.322

The Regulatory Subunit of PI3K Is a Direct Catalytic Target of SIK2. These data confirm that p85α is a direct catalytic substrate of SIK2 and that SIK2 S154 phosphorylation significantly increases the activity of the PI3K/AKT pathway in ovarian cancer cells.

SIGNOR-277269

Q13363

P31749

0

phosphorylation

down-regulates quantity

0.483

Co-expression of Pc2 and Akt1 results in both phosphorylation and ubiquitylation of CtBP1, thereby targeting CtBP1 for degradation.|CtBP1 phosphorylation by Akt1 appears to both decrease dimerization and induce ubiquitylation.

SIGNOR-278304

P53355

P04637

1

phosphorylation

up-regulates

0.558

Dna damage-activated protein kinases like chk1/2 modify the box-i domain of p53 at thr18 and ser20 (46) by an allosteric mechanism (10).

SIGNOR-153491

O95644

Q13627

0

phosphorylation

up-regulates activity

0.429

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

SIGNOR-278278

P45983

P49023

1

phosphorylation

up-regulates activity

0.676

JNK1 phosphorylates serine 178 on paxillin, a focal adhesion adaptor, both in vitro and in intact cells. NBT-II cells expressing the Ser 178 --> Ala mutant of paxillin (Pax(S178A)) formed focal adhesions and exhibited the limited movement associated with such contacts in both single-cell-migration and wound-healing assays. In contrast, cells expressing wild-type paxillin moved rapidly and retained close contacts as the predominant adhesion.

SIGNOR-250129

P28482

Q9H9Z2

1

phosphorylation

down-regulates activity

0.262

Here we show that Lin28a is directly phosphorylated by ERK1/2 kinases at Ser-200.

SIGNOR-277338

P04637

Q68DV7

0

ubiquitination

down-regulates quantity by destabilization

0.451

Moreover, RNF43 polyubiquitinates p53 which further leads to its destabilization resulting in a decrease in induction of the p53 apoptotic pathway, a hitherto unknown process targeted by NP for p53 stabilization and accumulation.

SIGNOR-278714

Q01094

Q13315

0

phosphorylation

up-regulates quantity by stabilization

0.679

Selective induction of e2f1 in response to dna damage, mediated by atm-dependent phosphorylation. We identify a site for atm/atr phosphorylation in the amino terminus of e2f1 and we show that this site is required for atm-mediated stabilization of e2f1. Finally, we also show that e2f1 is required for dna damaged induced apoptosis in mouse thymocytes.

SIGNOR-109416

Q9Y6I3

P00533

1

relocalization

down-regulates

0.596

Epsin 1 is involved in recruitment of ubiquitinated egf receptors into clathrin-coated pits this supports the contention that epsin 1 promotes endocytosis of the ubiquitinated egfr.

SIGNOR-182562

P17612

Q14978

1

phosphorylation

up-regulates

0.307

Here we demonstrate that protein kinase a (pka)-dependent phosphorylation of nopp140 at ser 627, together with c/ebpbeta, induces agp gene expression synergistically.

SIGNOR-91186

P51452

P43405

0

phosphorylation

up-regulates activity

0.363

ZAP-70 and Syk also tyrosine-phosphorylated VHR in COS-1 cells (Fig. 2d), whereas other kinases (Csk, Lck, Fyn, Jak2, Bcr-Abl and Itk) had little effect. Finally, recombinant ZAP-70 readily phosphorylated VHR in vitro (Fig. 2f).

SIGNOR-275999

Q6PJ69

Q9NRY4

1

polyubiquitination

down-regulates quantity by destabilization

0.2

Ubiquitin ligase TRIM65 promotes colorectal cancer metastasis by targeting ARHGAP35 for protein degradation

SIGNOR-272256

Q00987

O94992

1

ubiquitination

up-regulates activity

0.465

Here we report that human double minute-2 protein (HDM2), a p53-specific E3 ubiquitin ligase, specifically ubiquitinates HEXIM1 through the lysine residues located within the basic region of HEXIM1.|However, the HDM2-induced HEXIM1 ubiquitination does not lead to proteasome-mediated protein degradation.

SIGNOR-278701

Q9UK32

Q09472

1

phosphorylation

down-regulates activity

0.253

Figure 2G shows that Ser89 phosphorylation of p300, an event that inhibits p300’s acetyltransferase activity (13), was decreased in RSK4-silenced A549 and T24 cells. Consequently, RSK4 may regulate the activity of the NFκB pathway by direct phosphorylation of p300, as recombinant RSK4 phosphorylates p300 on Ser89 in vitro

SIGNOR-275796

O43561

Q13043

0

phosphorylation

up-regulates activity

0.2

MST kinase phosphorylates and activates LATS kinase.

SIGNOR-279661

P19174

P04629

0

phosphorylation

up-regulates

0.652

The nerve growth factor (ngf) receptor/trk associated with and phosphorylated phospholipase c gamma (plc gamma)

SIGNOR-38538

P08670

P53350

0

phosphorylation

up-regulates

0.2

We observed that plk1 phosphorylates vimentin on ser82, which in turn regulates cell surface levels of 1 integrin.

SIGNOR-159386

P20701

O60674

0

phosphorylation

up-regulates activity

0.268

PTKs of the JAK and SRC families have a regulatory role in LFA-1 affinity triggering, with JAKs showing a positive role (3), whereas SRCs possibly have a negative role.

SIGNOR-254739

P21754

Q5JUK2

0

transcriptional regulation

up-regulates quantity by expression

0.378

Cotransfection of a mouse Sohlh1 expression vector with E box-containing promoter regions of mouse Lhx8, Zp1, and Zp3 fused to luciferase resulted in significant transactivation . Mutation of the E box sequences abolished SOHLH1-dependent stimulation. Thus, Lhx8, Zp1, and Zp3 are likely direct downstream target genes of SOHLH1 through the E box elements in their promoters.

SIGNOR-266078

P62136

Q70Z35

1

dephosphorylation

up-regulates activity

0.2

PREX2 is dephosphorylated by PP1α and PP2A.PAK-mediated phosphorylation of PREX2 reduced GEF activity toward Rac1 by inhibiting PREX2 binding to PIP3 and Gβγ.

SIGNOR-277183

Q86YD1

Q96BR1

0

phosphorylation

down-regulates quantity by destabilization

0.2

In this study, we find that the understudied serum and glucocorticoid-induced kinase-2 (SGK2) phosphorylates PTOV1 at S36.

SIGNOR-279283

Q13315

P17096

1

phosphorylation

up-regulates activity

0.2

21 As shown in Fig. 2 b, ATM was able to phosphorylate in vitro the C-terminal peptide of HMGA1.

SIGNOR-279493

Q8IUQ4

P49757

1

ubiquitination

down-regulates

0.4

We report that siah-1 interacts directly with and promotes the degradation of the cell fate regulator numb.

SIGNOR-113469

O95714

Q96JN8

1

polyubiquitination

down-regulates quantity by destabilization

0.456

NEURL4 is a substrate of HERC2, and together these results indicate that the NEURL4-HERC2 complex participates in the ubiquitin-dependent regulation of centrosome architecture.

SIGNOR-272921

P35790

Q00987

1

phosphorylation

down-regulates quantity by destabilization

0.274

The data presented here provides evidence for a molecular mechanism by which CKI-dependent phosphorylation of Mdm2 at multiple sites triggers SCF \u03b2-TRCP -mediated Mdm2 destruction ( xref ).

SIGNOR-279606

Q00653

O15111

0

phosphorylation

up-regulates activity

0.791

Ikkalfa phosphorylates p100, leading to its proteasomal processing to p52.

SIGNOR-124230

P15172

Q14469

0

transcriptional regulation

down-regulates activity

0.294

Notch signaling up-regulated HES1 mRNA expression within 1 h and subsequently reduced expression of MyoD mRNA

SIGNOR-243181

O95863

Q9NRM7

0

phosphorylation

up-regulates

0.528

Lats2 kinase potentiates snail1 activity by promoting nuclear retention upon phosphorylation. during tgf_-induced emt lats2 is activated and snail1 phosphorylated at t203.

SIGNOR-176647

P06493

P33991

1

phosphorylation

down-regulates activity

0.592

We report here that human mcm4, a subunit of the putative dna replicative helicase, is extensively phosphorylated in hela cells when they are incubated in the presence of inhibitors of dna synthesis or are exposed to uv irradiation. The data presented here indicate that the consecutive actions of atr-chk1 and cdk2 kinases are involved in this phosphorylation in the presence of hydroxyurea. Phosphorylation of t19 correlates with lowered level of dna helicase activity of the purified mcm4,6,7 complex.

SIGNOR-100877

Q8IXH7

P12931

0

phosphorylation

down-regulates activity

0.336

Here we show that c-Src interacts with TH1 by GST-pull down assay, coimmunoprecipitation and confocal microscopy assay. The interaction leads to phosphorylation of TH1 at Tyr-6 in vivo and in vitro. Phosphorylation of TH1 decreases its association with A-Raf and PAK1.

SIGNOR-276402

P49841

P25054

1

phosphorylation

up-regulates

0.758

Gsk-3beta-dependent phosphorylation of apc.

SIGNOR-75366

P50553

Q9HCK8

0

transcriptional regulation

down-regulates quantity

0.2

Many of the most significantly up-regulated genes in Chd8+/− and Chd8−/− NPCs are involved in later stages of neuronal development, including Ascl1 [a central driver of neural reprogramming (29)], Dcx, Map2, Nefm, Neurod4, and Neurog1 (Fig. 2 E and F). Additionally, we found that Sox3 is derepressed in both Chd8+/− and Chd8−/− NPCs, and several other Sox TF members (Sox2, Sox7, and Sox11) became derepressed in the Chd8−/− cells

SIGNOR-268914

P01106

P30304

1

transcriptional regulation

up-regulates quantity by expression

0.627

Expression of Cdc25A is transcriptionally regulated by Myc and E2F-1 , both of which are expressed in MCF-7 cells in response to estrogen

SIGNOR-245465

P07814

Q00535

0

phosphorylation

down-regulates

0.2

Ser(886) phosphorylation is required for the interaction of nsap1, which blocks eprs binding to target mrnas. The same phosphorylation event induces subsequent binding of ribosomal protein l13a and gapdh and restores mrna binding. Ifn-_ activates cdk5 to phosphorylate ser(886) in the linker domain of glutamyl-prolyl trna synthetase (eprs), the initial event in assembly of the gait complex. Cdk5/p35 also induces, albeit indirectly via a distinct kinase, phosphorylation of ser(999), the second essential event in gait pathway activation

SIGNOR-187383

Q9UQM7

Q05682

1

phosphorylation

down-regulates

0.2

Smooth muscle caldesmon was phosphorylated by smooth muscle calmodulin-dependent protein kinase. Ii

SIGNOR-22635

Q15910

Q9P275

0

deubiquitination

up-regulates quantity by stabilization

0.2

We observed a MELK-mediated increase of EZH2 S220 phosphorylation along with a concomitant loss of EZH2 K222 ubiquitination, suggesting a phosphorylation-dependent regulation of EZH2 ubiquitination. Furthermore, we identify USP36 as the deubiquitinating enzyme that deubiquitinates EZH2 at K222.

SIGNOR-277481

P46531

P49336

0

phosphorylation

down-regulates

0.552

Purified recombinant cycc:cdk8 phosphorylates the notch icd within the tad and pest domains, and expression of cycc:cdk8 strongly enhances notch icd hyperphosphorylation and pest-dependent degradation by the fbw7/sel10 ubiquitin ligase in vivo.

SIGNOR-130640

O14757

P30305

1

phosphorylation

down-regulates activity

0.785

Here, we show that cdc25b is phosphorylated by chk1 in vitro on multiple residues, including s230 and s563.We show that the s230-phosphorylated form of cdc25b is located at the centrosome from early s phase until mitosis. Furthermore, mutation of s230 to alanine increases the mitotic-inducing activity of cdc25b

SIGNOR-149898

Q9NSC5

Q9UQM7

0

phosphorylation

down-regulates activity

0.2

Homer3 is phosphorylated at Ser120, Ser159, and Ser176 by CaMKII in vitro. Homer3 phosphorylation reduces its affinity for target molecules and modulates the Ca2+ signaling patterns induced by mGluR1α activation

SIGNOR-262685

Q9Y4K3

Q9BQ95

1

ubiquitination

down-regulates activity

0.79

Here we demonstrate that engagement of a subset of Toll-like receptors (TLR1, TLR2 and TLR4) results in the recruitment of mitochondria to macrophage phagosomes and augments mROS production. This response involves translocation of a TLR signalling adaptor, tumour necrosis factor receptor-associated factor 6 (TRAF6), to mitochondria, where it engages the protein ECSIT (evolutionarily conserved signalling intermediate in Toll pathways), which is implicated in mitochondrial respiratory chain assembly. Interaction with TRAF6 leads to ECSIT ubiquitination and enrichment at the mitochondrial periphery, resulting in increased mitochondrial and cellular ROS generation

SIGNOR-260370

Q96FI4

Q12899

0

ubiquitination

down-regulates quantity

0.247

Mule and TRIM26 ubiquitylate NEIL1 in vitro within C-terminal lysine residues.|Similar to these previous results, we again demonstrate that a knockdown of Mule or TRIM26 causes an elevation in the protein stability of NEIL1 in comparison to non-targeting siRNA, unirradiated control (Figure and ; compare lanes 1 and 2).

SIGNOR-278647

P51784

P68104

1

deubiquitination

up-regulates activity

0.2

USP11 interacted with and deubiquitinated eEF1A1 on Lys439, thereby inhibiting its ubiquitin-mediated degradation. Subsequently, the elevated expression of eEF1A1 resulted in its binding to SP1, which in turn drove the binding of SP1 to its target HGF gene promoter to increase its transcription

SIGNOR-278107

O14920

P23396

1

phosphorylation

up-regulates activity

0.332

IKKbeta overexpression activated NF-kappaB measured by luciferase assays , and also induced the nuclear translocation of wild-type, but not S209A, RPS3 (XREF_FIG).|Therefore, RPS3 S209 phosphorylation by IKK\u03b2 is apparently required for RPS3 in directing NF-\u03baB to a specific subset of target genes.

SIGNOR-278360

P49336

P42224

1

phosphorylation

up-regulates activity

0.392

We previously demonstrated that Mediator kinase inhibitor cortistatin A (CA) reduced proliferation of JAK2-mutant AML in vitro and in vivo and also suppressed CDK8-dependent phosphorylation of STAT1 at serine 727. Here we report that phosphorylation of STAT1 S727 promotes the proliferation of AML cells with JAK-STAT pathway activation.

SIGNOR-273179

Q9NR28

O15033

0

ubiquitination

down-regulates quantity by destabilization

0.377

AREL1 ubiquitinated SMAC, primarily on Lys62 and Lys191 |E701A substitution in the AREL1 HECT domain substantially increased its autopolyubiquitination and SMAC ubiquitination activity, whereas deletion of the last three amino acids at the C terminus completely abrogated AREL1 autoubiquitination and reduced SMAC ubiquitination.

SIGNOR-267672

P17252

P48730

1

phosphorylation

up-regulates activity

0.2

In the present study we analyzed the CK1δ kinase domain for phosphorylation sites targeted by PKCα. Several phosphorylation sites were identified in vitro by initially using GST-CK1δ wild type and phosphorylation-site mutant protein fragments originating from the CK1δ kinase domain. Residues S53, T176, and S181 could finally be confirmed as targets for PKCα. Determination of kinetic parameters of full-length wild type and mutant GST-CK1δ-mediated substrate phosphorylation revealed that integrity of residue T176 is crucial for maintaining CK1δ kinase activity.

SIGNOR-277452

P68400

Q9UD71

1

phosphorylation

up-regulates activity

0.34

Study of [Plphosphate release during manual Edman degradation confirmed that the phosphorylated residues in rat DARPP-32 were Ser45 and Ser102. | Phosphorylation by casein kinase II did not affect the potency of DARPP-32 as an inhibitor of protein phosphatase-1, which depended only on phosphorylation of Thr34 by cAMP-dependent protein kinase. However, phosphorylation of DARPP-32 by casein kinase II facilitated phosphorylation of Thr34 by cAMP-dependent protein kinase

SIGNOR-250927

P68431

Q92831

0

acetylation

down-regulates activity

0.2

The HAT module within the SAGA and ADA complexes acetylates histone H3, mainly on residues K9 and K14.

SIGNOR-269611

Q16695

Q9C0A6

0

methylation

up-regulates activity

0.2

SETD5 Exhibits Intrinsic Methyltransferase Activity on H3K36. This assay showed that SETD5 has specific histone methyltransferase activity toward K36 but not for other residues such as K4 and K27 (Figure 8B). we revealed that SETD5 is endowed with H3K36 methyltransferase, which is necessary for RNA elongation and processing and, ultimately, correct gene transcription.

SIGNOR-264621

O95476

Q14693

1

dephosphorylation

up-regulates activity

0.78

Dullard significantly dephosphorylates mouse lipin 1b only in BHK cells (Fig. 5A). This is most clearly seen by using the antibody prepared against the phosphorylation site Ser-106.|Dephosphorylation of lipin results in its translocation to the nuclear envelope and endoplasmic reticulum membranes from the cytosol and generation of diacylglycerol

SIGNOR-248346

Q04759

Q9Y4G8

1

phosphorylation

up-regulates

0.2

After t-cell activation, the direct phosphorylation of rapgef2 at ser960 by pkc- theta regulates rap1 activation as well as lfa-1 adhesiveness to icam-1. Pkc- theta and its effector rapgef2 are critical factors in tcr signaling to rap1

SIGNOR-181186

Q04759

Q8IV61

1

phosphorylation

up-regulates

0.328

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

SIGNOR-130490

P46531

Q13627

0

phosphorylation

down-regulates

0.396

Dyrk1a physically interacts with the nicd inducing its phosphorylation in the ankyrin domain, thereby attenuating notch .

SIGNOR-185494

P35968

P62993

1

relocalization

up-regulates activity

0.686

In a similar fashion, KDR associates with Grb2 and Nck in a ligand-dependent fashion, suggesting Shc, Grb2, and Nck as potential candidates involved in the regulation of endothelial function.

SIGNOR-261948

P46020

P17612

0

phosphorylation

up-regulates activity

0.432

Phosphorylation of the alpha and beta subunits by the 3',5'-cyclic adenosine monophosphate (cAMP)-dependent protein kinase (PKA) also relieves inhibition of the gamma subunit and thereby activates the enzyme.

SIGNOR-267411

P05412

P68400

0

phosphorylation

down-regulates

0.592

Casein kinase ii is a negative regulator of c-jun dna binding and ap-1 activitywe show that two of these sites, thr-231 and ser-249, are phosphorylated by casein kinase ii (ckii).

SIGNOR-19607

Q6ZVD8

P23443

1

dephosphorylation

down-regulates activity

0.49

We show that PHLPP preferentially dephosphorylates the hydrophobic motif T389 site in S6K1 in vitro

SIGNOR-248247

P21802

P62993

1

phosphorylation

up-regulates

0.773

Inhibition of basal fgf receptor signaling by dimeric grb2.

SIGNOR-197980

P53355

P98161

1

phosphorylation

up-regulates activity

0.2

In addition, the tumor suppressor death-associated protein kinase phosphorylates and activates PKD1 in response to oxidative damage ( xref ).

SIGNOR-279985

Q8IVM0

P00533

0

phosphorylation

down-regulates activity

0.415

We also detected tyrosine phosphorylation of Ymer by EGF stimulation as previously reported (Fig. 1A). Furthermore, we verified that EGF receptor-mediated tyrosine phosphorylation of Ymer is inhibited by AG1478, which is known as an EGF receptor tyrosine kinase inhibitor (Fig. 1B). A luciferase reporter assay showed that mutation of tyrosines on Ymer (YmerY217/279/304F) results in loss of the inhibitory activity for NF-kappaB signaling.

SIGNOR-262851

Q05639

P45983

0

phosphorylation

down-regulates quantity by destabilization

0.374

Ribosome-associated JNK phosphorylates the eukaryotic translation elongation factor 1A isoform 2 (eEF1A2) on serines 205 and 358 to promote degradation of NSPs by the proteasome.

SIGNOR-276492

Q9HAT8

Q96P20

1

ubiquitination

up-regulates activity

0.2

Pellino2 promotes ubiquitination of NLRP3.|We now demonstrate that Pellino2 can promote increased production of mature bioactive IL-1beta by facilitating activation of the NLRP3 inflammasome.

SIGNOR-278525

P25116

P00747

0

cleavage

down-regulates activity

0.624

Plasmin mediates the lysis of fibrin clots and could in different studies activate platelets or inhibit the responses induced by thrombin (41-43). Our study favors a net inactivating effect on PAR1 despite minor cleavage at Arg41, on the basis of preferential cleavage at positions Arg70 and Lys76, COOH-terminal to the Arg41-Ser42 activation site.

SIGNOR-263572

Q16611

Q9NR28

1

relocalization

up-regulates

0.522

Bax and/or bak-mediated release of pro-apoptotic mediators including smac/diablo and omi

SIGNOR-118905

P46934

Q9Y4G8

1

ubiquitination

down-regulates quantity

0.401

In line with the previous result (XREF_FIG), overexpression of NEDD4-1 reduced the level of CNrasGEF significantly (XREF_FIG).|NEDD4-1 ubiquitinates CNrasGEF in glioma cells.

SIGNOR-278705

Q12800

P28482

0

phosphorylation

down-regulates

0.335

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

SIGNOR-184168

P49327

P19474

0

ubiquitination

down-regulates quantity by destabilization

0.2

FASN acetylation enhanced its association with the E3 ubiquitin ligase TRIM21. Acetylation destabilized FASN and resulted in decreased de novo lipogenesis and tumor cell growth. FASN acetylation was frequently reduced in human hepatocellular carcinoma samples, which correlated with increased HDAC3 expression and FASN protein levels.

SIGNOR-267368

Q13163

P10912

0

phosphorylation

up-regulates activity

0.2

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

SIGNOR-255452

Q13459

P61586

1

gtpase-activating protein

down-regulates activity

0.774

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-260509

P41208

Q92949

0

transcriptional regulation

up-regulates quantity by expression

0.353

FOXJ1 expression in basal cells induced the expression of a panel of cilia-associated genes, including centrin 2 (CETN2); dynein, axonemal, heavy chain 11 (DNAH11); dynein, axonemal, intermediate chain 1 (DNAI1); dynein, axonemal, light intermediate chain 1 (DNALI1); EF-hand domain, C-terminal, containing 1 (EFHC1); sperm associated antigen 6 (SPAG6); tektin 1 (TEKT1), TEKT2 and tubulin, alpha 1a (TUBA1A; Figure 3C and Additional file 2: Table S1).

SIGNOR-266930

Q9NS23

Q13315

0

phosphorylation

up-regulates

0.549

We show that, upon dna damage, rassf1a is phosphorylated by atm on ser131 and is involved in the activation of both mst2 and lats1, leading to the stabilization of p73.

SIGNOR-161934

Q13315

P06748

1

phosphorylation

up-regulates activity

0.352

In addition to Serine 125, ATM may also phosphorylate other sites on NPM.

SIGNOR-280182

Q13153

P53667

1

phosphorylation

up-regulates activity

0.614

Activation of lim-kinase by pak1 couplesp21-activated kinase (pak1) phosphorylates lim-kinase at threonine residue 508 within lim-kinase's activation loop

SIGNOR-72142

P49327

Q5VWC8

0

chemical activation

up-regulates activity

0.2

Very long-chain fatty acids are produced through a four-step cycle. However, the 3-hydroxyacyl-CoA dehydratase catalyzing the third step in mammals has remained unidentified. Mammals have four candidates, HACD1-4, based on sequence similarities to the recently identified yeast Phs1, although HACD3 and HACD4 share relatively weak similarity. We demonstrate that all four of these human proteins are indeed 3-hydroxyacyl-CoA dehydratases,

SIGNOR-267763

Q13627

P53805

1

phosphorylation

up-regulates

0.562

In the present study, dyrk1a is shown to directly interact with and phosphorylate rcan1 at ser112 and thr192 residues. Dyrk1a-mediated phosphorylation of rcan1 at ser112 primes the protein for the gsk3_-mediated phosphorylation of ser108.

SIGNOR-102290

P46940

P17252

0

phosphorylation

up-regulates

0.258

Using a mass spectrometry-based assay, we show that egf induces phosphorylation of iqgap1 ser(1443), a residue known to be phosphorylated by pkcthe nonphosphorylatable iqgap1 s1441a/s1443a had no effect. In contrast, the s1441e/s1443d mutation markedly enhanced the ability of iqgap1 to induce neurite outgrowth.

SIGNOR-128714

Q05516

P24941

0

phosphorylation

down-regulates

0.282

Here we show that the main cyclin-dependent kinase involved at the g(1) to s transition (cdk2) phosphorylates plzf at two consensus sites found within pest domains present in the hinge region of the protein. This phosphorylation triggers the ubiquitination and subsequent degradation of plzf, which impairs plzf transcriptional repression ability and antagonizes its growth inhibitory effects.

SIGNOR-160630

Q00535

Q8N5V2

1

phosphorylation

up-regulates activity

0.42

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

SIGNOR-279021

P15336

Q9H4B4

0

phosphorylation

up-regulates

0.2

Phosphorylation of thr-69 by mapk14 and mapk11, and at thr-71 by mapk1/erk2, mapk3/erk1, mapk11, mapk12 and mapk14 in response to external stimulus like insulin causes increased transcriptional activity.

SIGNOR-163274

P17612

Q2Q1W2

1

phosphorylation

up-regulates quantity by stabilization

0.2

These observations suggested that LINK-A expression potentially inhibits PKA phosphorylation/activity and PKA-mediated phosphorylation of TRIM71 at Ser3.

SIGNOR-277454

P12931

Q9H7P9

1

phosphorylation

up-regulates activity

0.2

Through deletion and base substitution mutagenesis we have identified Tyr489 of PLEKHG2 as the site phosphorylated by cSrc.The interaction between PLEKHG2 and the full-length of PIK3R3, but not ABL1, occurs in a tyrosine-phosphorylation-dependent manner.

SIGNOR-273808

Q14289

P29474

1

phosphorylation

down-regulates

0.309

We found that fluid shear stress induces the association of enos with the proline-rich tyrosine kinase 2 (pyk2) in endothelial cells and that the enos immunoprecipitated from enos- and pyk2-overexpressing hek293 cells was tyrosine-phosphorylated on tyr657.

SIGNOR-161824

P15498

P00519

0

phosphorylation

up-regulates

0.401

Thus, the c-terminal tail of vav serves as a direct substrate of bcr-abl in vitro.

SIGNOR-114091

Q05655

P23396

1

phosphorylation

up-regulates activity

0.2

Here we show that PKCδ phosphorylates rpS3 resulting in its mobilization in the nucleus to repair damaged DNA

SIGNOR-260895

Q9HB09

P49841

0

phosphorylation

up-regulates

0.338

Gsk3b phosphorylates bcl2l12 at s156. Ectopic expression of gfp-fused bcl2l12 or bcl2l12a in u87mg cells leads to repression of apoptotic markers and protects against staurosporine (sts) insults, indicating an antiapoptotic role for both bcl2l12 and bcl2l12a. In contrast, no anti-apoptotic ability was seen in bcl2l12(s156a)

SIGNOR-195512

P53778

P04637

1

phosphorylation

up-regulates activity

0.474

Furthermore, upon activation by oncogenic ras, p38gamma stimulated the transcriptional activity of p53 by phosphorylating p53 at Ser(33), suggesting that the ability of p38gamma to mediate senescence is at least partly achieved through p53.

SIGNOR-280026

Q9H4B4

P16104

1

phosphorylation

up-regulates activity

0.2

Phosphorylation of H2AX at serine 139 was catalyzed by hyperosmotic stress-induced activation of Plk3.|Osmotic stress induced phosphorylation of H2AX by polo like kinase 3 affects cell cycle progression in human corneal epithelial cells.|Our results for the first time reveal that hyperosmotic stress-activated Plk3 elicited \u03b3H2AX.

SIGNOR-280073

P13807

P17612

0

phosphorylation

down-regulates activity

0.508

The results presented in this paper show that the phosphorylation of glycogen synthetase a by cyclic AMP-dependent protein kinase results in the phosphorylation of two distinct serines termed site-l and site-2, which account for 90% of the total phosphorylation

SIGNOR-253009

P16591

Q05397

1

phosphorylation

up-regulates activity

0.251

The Fer mediated phosphorylation of specific tyrosine residues of FAK was abolished by cotransfection of shRNA against Fer (i.e., shFer), but not by control shRNA, indicating that the phosphorylation of Tyr577, 861, or 925 of FAK in suspended cells was indeed caused by Fer.

SIGNOR-279409

Q15811

P60953

1

guanine nucleotide exchange factor

up-regulates activity

0.848

Significantly, here we identify the long isoform of ITSN-1, which has Cdc42 GEF activity| We propose that GCC88 recruits ITSN-1-L to the TGN, which in turn activates Cdc42 at the trans-face of the Golgi (Figure 9A).

SIGNOR-260612

P35790

Q14693

1

phosphorylation

down-regulates activity

0.273

Because CKI is a constitutively active kinase and ubiquitously distributed in many cell types, high mTORC1 activity depending on nutritional status may be a physiological cue for Lipin1 degradation mediated by CKI and beta-TRCP.|Thus, we propose that mTORC1 may function as a priming kinase for CKI to promote the phosphorylation of the degron motif in Lipin1.

SIGNOR-280228

Q13794

P30679

1

phosphorylation

up-regulates activity

0.2

Ga16 is phosphorylated in vivo by PMA and by TRH receptor stimulation

SIGNOR-278131

Q7L7X3

P46734

1

phosphorylation

up-regulates activity

0.578

The activation of and binding to MEK3 by TAO1 implicates TAO1 in the regulation of the p38-containing stress-responsive MAP kinase pathway

SIGNOR-60818