GleghornLab/Signor_2class · Datasets at Hugging Face

IdA string	IdB string	labels int64	mechanism string	effect string	score float64	sentence string	signor_id string
O00308	P60484	1	ubiquitination	down-regulates quantity by destabilization	0.632	We have shown that WWP2 interacts with and ubiquitylates PTEN, promoting its degradation.	SIGNOR-278650
Q14676	P68400	0	phosphorylation	up-regulates	0.346	The mdc1-nbs1 interaction occurs through a specific region (residues 200-420) of mdc1, which contains multiple consensus casein kinase 2 (ck2) phosphorylation sites.	SIGNOR-179887
P49757	Q2M2I8	0	phosphorylation	up-regulates	0.459	Collectively, these observations demonstrate that numb endocytic activity is regulated by aak1 and that phosphorylation may be a critical step in promoting coated pit maturation.	SIGNOR-179606
P25490	P53350	0	phosphorylation	up-regulates	0.392	More recently, we identified and mapped multiple phosphorylation sites in yy1, including, threonine 39, serine 118, serine 247, threonine 348 and threonine 378. The first kinase proven to phosphorylate yy1 in vivo was plk1, which phosphorylates threonine 39 during g2/m stage of the cell cycle [25]. Ck2_ is another kinase identified as constitutively phosphorylating yy1 at serine 118. This modification protects yy1 cleavage by caspase 7 during apoptosis	SIGNOR-200087
P28482	Q05682	1	phosphorylation	down-regulates	0.539	Extracellular signal-regulated kinases (erks) phosphorylate the high molecular mass isoform of the actin-binding protein caldesmon (h-cad) at two sites (ser(759) and ser(789)) during smooth muscle stimulation. Nmr spectroscopy shows that the actin binding properties of the minimal inhibitory region of caldesmon, residues 750-779, alter upon map kinase phosphorylation of ser-759, a residue not involved in actin binding. This phosphorylation leads to markedly diminished actin affinity as a result of the loss of interaction at one of the two sites that bind to f-actin.	SIGNOR-71037
Q15078	Q9H0K1	0	phosphorylation	down-regulates	0.331	Sik2 phosphorylates p35 at ser 91, to trigger its ubiquitylation by pja2 and promote insulin secretion. _-cell knockout of sik2 leads to accumulation of p35 and impaired secretion	SIGNOR-204648
Q13115	P27361	1	dephosphorylation	down-regulates activity	0.709	Dephosphorylation and Inactivation of ERKs\|ERK1 phosphorylated on either threonine (ERK1Y204F) or tyrosine alone (ERK1T202A) was utilized as a substrate for HVH2. Threonine 202 and tyrosine 204 in ERK1 (53) correspond to threonine 183 and tyrosine 185 in ERK2 which are the activation-phosphorylation sites by MEK(14, 15, 16). ERK1, a kinase-deficient mutant, was phosphorylated on both threonine and tyrosine by MEK2 (Fig. 3B). ERK1T202A, having threonine 202 substituted by an alanine, was phosphorylated only on tyrosine while ERK1Y204F, having tyrosine 204 substituted by a phenylalanine, was phosphorylated only on threonine (Fig. 3B). GST-HVH2 dephosphorylated all three ERK1 mutants (Fig. 3A), suggesting that double phosphorylations of adjacent threonine and tyrosine were not a prerequisite for HVH2 recognition. However, HVH2 dephosphorylated ERK1* and ERK1T202A more efficiently than ERK1Y204F (Fig. 3A), indicating that HVH2 preferred phosphotyrosine over phosphothreonine. Interestingly, MEK also phosphorylated tyrosine residues more efficiently than threonine residues of ERK	SIGNOR-248716
Q00987	Q13761	1	ubiquitination	down-regulates quantity by destabilization	0.579	RUNX3 protein is ubiquitinated by MDM2 at Lys-94 and Lys-148.\|RUNX3 protein is ubiquitinated by MDM2 at Lys 94 and Lys 148.\|MDM2 suppresses the transcriptional activity of RUNX3.	SIGNOR-278557
Q9UGP5	Q7Z6Z7	0	polyubiquitination	down-regulates quantity by destabilization	0.309	We found that Pol λ can be ubiquitinated by the E3 ligase Mule in vitro and in vivo and that this interaction is functionally connected to the phosphorylation-dependent stabilization of Pol λ by Cdk2/cyclinA.	SIGNOR-272904
P35222	Q5VWQ8	0	relocalization	down-regulates quantity	0.299	DAB2IP prevents β-catenin nuclear translocation.	SIGNOR-254755
Q8N726	Q14669	0	ubiquitination	down-regulates quantity by destabilization	0.582	ULF interacts with ARF both in vitro and in vivo and promotes the lysine-independent ubiquitylation and degradation of ARF.	SIGNOR-266781
P10070	Q9Y297	0	ubiquitination	down-regulates quantity by destabilization	0.651	The phosphorylated gli2 protein interacts with beta-trcp, and is ubiquitinated and degraded by the proteasome	SIGNOR-146109
Q15759	P30281	1	phosphorylation	down-regulates quantity by destabilization	0.2	P38SAPK2 phosphorylates cyclin D3 at Thr-283 and targets it for proteasomal degradation.	SIGNOR-280023
Q86U70	Q9NVW2	0	polyubiquitination	down-regulates quantity by destabilization	0.566	Here we identify RLIM as a ubiquitin protein ligase that is able to target CLIM cofactors for degradation through the 26S proteasome pathway.	SIGNOR-272617
O43318	Q15797	1	phosphorylation	up-regulates activity	0.373	This analysis showed that phosphorylation of Smad1 at the C-terminal serines S463 and S465 was increased by co-expression of constitutively active TAK1.	SIGNOR-279419
Q15910	P49841	0	phosphorylation	down-regulates activity	0.33	GSK3beta phosphorylates EZH2 at Ser363 and Thr367 in vitro, and activating GSK3beta upregulates Thr367 phosphorylationin vivo.	SIGNOR-278176
Q13085	Q13131	0	phosphorylation	down-regulates activity	0.7	We have isolated and purified from rat livers a novel kinase that phosphorylates and inactivates the carboxylase Ser1200 isphosphorylated by both CAMP-dependent protein kinase and AMP-activated protein kinase	SIGNOR-250400
Q7L591	P07948	0	phosphorylation	up-regulates activity	0.409	An adaptor protein Dok-3 mediates the suppressive function of LYN. The Dok-3 phosphorylated by LYN upon BCR stimulation forms a complex with GRB2, which allows it to enter into the signalosome and associate with activation of SHIP protein. This translocation facilitates the efficient inhibition of PLCc2 and SYK from activation, subsequently resulting in the suppression of downstream Ca2+ signaling.	SIGNOR-268447
P50281	Q13443	1	cleavage	down-regulates quantity by destabilization	0.341	Here we show that MT1-MMP forms a complex with FGFR2 and ADAM9 in osteoblasts and proteolytically inactivates ADAM9\|Western blotting using antibodies against ectodomain of ADAM9 detected a fragment (around 26 kDa) of ADAM9 in the conditioned culture medium from cells cotransfected with wild-type MT1-MMP, but not in that with catalytic activity-dead MT1-MMP (Figure 6A, top).	SIGNOR-260301
P02511	Q92481	0	transcriptional regulation	up-regulates quantity by expression	0.2	Aberrant expression of CRYAB has been shown to be associated with several neurological diseases and malignant neoplasms. To identify transcriptional regulators of CRYAB expression, we examined its promoter for binding sites of transcription factors and identified four potential AP-2 binding sites in addition to a p53 binding site reported previously\|Taken together, our results indicate that AP-2_ up-regulates the transcription of the CRYAB gene through stabilizing p53	SIGNOR-253637
P06239	P20138	1	phosphorylation	up-regulates	0.271	Human cd33 has two tyrosine residues in its cytoplasmic domain (y340 and y358). When phosphorylated, these tyrosines could function as docking sites for the phosphatases, shp-1 and/or shp-2, enabling cd33 to function as an inhibitory receptor. Lck is effective at phosphorylating y340	SIGNOR-78960
P11309	Q04206	1	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
O15392	Q8IWT3	0	ubiquitination	down-regulates quantity	0.489	CUL9 promotes the ubiquitylation and degradation of survivin and is inhibited by CUL7.\|Together, these results demonstrate the specificity of survivin ubiquitylation by CUL9 E3 ligase complex.	SIGNOR-278808
Q15796	Q96PU5	0	ubiquitination	down-regulates activity	0.781	Through its ww domain, nedd4l specifically recognizes a tgf-beta-induced phosphothr-protyr motif in the linker region, resulting in smad2/3 polyubiquitination and degradation	SIGNOR-217622
P19174	Q16620	0	phosphorylation	up-regulates activity	0.647	Both Shc and PLCgamma1 are phosphorylated by TrkB, thereby initiating Shc/Ras/MAP kinase and PLCgamma1 signaling respectively.\|We conclude that activation of pY783 PLCgamma1 is due mainly to TrkB activation in these models and that TrkB induced PLCgamma1 signaling promotes limbic epileptogenesis.	SIGNOR-279241
O75531	P60510	0	dephosphorylation	up-regulates	0.2	Herein, we demonstrate we demonstrate that phosphorylation of ser4 and/or thr2/thr3 abrogates the interaction of baf with dna and reduces its interaction with the lem domain. We have identified the major phosphatase responsible for dephosphorylation of ser-4 to be protein phosphatase 4 catalytic subunit.	SIGNOR-203281
Q13263	Q05655	0	phosphorylation	down-regulates	0.2	This work demonstrates that tif1beta is phosphorylated on ser473, the alteration of which is dynamically associated with cell cycle progression and functionally linked to transcriptional regulation. Phosphorylation of tif1beta/ser473 is mediated by the pkcdelta pathway and is closely linked to cell proliferation. Phosphorylation of tif1beta/ser473 coincides with the induction of cell cycle gene cyclin a2 at the s-phase. Promoter of cyclin a2 gene is occupied by tif1beta and such occupancy is inversely correlated with ser473 phosphorylation. Non-phosphorylated tif1beta/ser473 allowed greater tif1beta association with the regulatory regions and the consequent repression of these genes.	SIGNOR-179250
P17612	P12931	1	phosphorylation	up-regulates activity	0.361	PKA activated Src both in vitro and in vivo by phosphorylating Src on serine 17 within its amino terminus	SIGNOR-247988
Q13485	P49841	0	phosphorylation	down-regulates quantity by destabilization	0.398	In the presence of FGF, Wnt potentiates TGF-β signaling by preventing Smad4 GSK3 phosphorylations that inhibit a transcriptional activation domain located in the linker region.	SIGNOR-276440
P08151	Q96J02	0	ubiquitination	down-regulates	0.578	The consequent activation of_ itch, together with the recruitment of gli1 through direct binding with_ numb, allows gli1 to enter into the complex, resulting in gli1 ubiquitination and degradation. we demonstrate that the hedgehog transcription factor gli1 is targeted by numb for itch-dependent ubiquitination, which suppresses hedgehog signals, thus arresting growth and promoting cell differentiation	SIGNOR-150847
Q13043	O43561	1	phosphorylation	up-regulates activity	0.2	MST kinase phosphorylates and activates LATS kinase.	SIGNOR-279661
Q9NWQ8	P06241	0	phosphorylation	up-regulates activity	0.703	Thus, Fyn mediates Csk-binding protein-Csk interaction and recruits Csk to rafts by phosphorylating Csk-binding protein.	SIGNOR-279987
P08246	P55085	1	cleavage	down-regulates activity	0.395	PAR1E and PAR2E (10 microM) were incubated in the presence of the different proteases \| The enzymes were used at the following concentrations: 0.5 unit/mL thrombin, 2.5 nM trypsin, 20 nM plasmin, 20 nM cathepsin G, 20 nM elastase, 20 nM proteinase 3, and 2 units/mL calpain I and II\|Protease-activated receptors (PARs) mediate cell activation after proteolytic cleavage of their extracellular amino terminus.\|Mass spectrometry studies of PAR2E predicted activation of PAR2 by trypsin through cleavage at the Arg36-Ser37 site, no effect of thrombin, and inactivation of the receptor by plasmin, calpain and leukocyte elastase, cathepsin G, and proteinase 3	SIGNOR-263588
P63000	Q13459	0	gtpase-activating protein	down-regulates activity	0.541	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-260510
Q9H0B6	Q13131	0	phosphorylation	up-regulates	0.2	Consistent with phosphorylation of both ser545 and ser582 of klc2 contributing to its 14-3-3 binding, a ser545ala mutant of klc2 could be phosphorylated in vitro by ampk on ser582	SIGNOR-174681
P01106	P15884	0	transcriptional regulation	up-regulates quantity by expression	0.371	Association of c-Jun, β-catenin, and TCF4 specifically with the downstream enhancer underlies mitogen stimulation of c-Myc transcription.	SIGNOR-253324
P28482	P49795	1	phosphorylation	up-regulates	0.474	Phosphorylation of gaip by erk2 were abrogated when serine at position 151 in the rgs domain was substituted by an alanine residue using site-directed mutagenesis. Furthermore, the lysosomal-autophagic pathway was not stimulated in s151a-gaip mutant-expressing cells when compared with wild-type gaip-expressing cells. These results demonstrate that the gtpase-activating protein activity of gaip is stimulated by erk2 phosphorylation.	SIGNOR-129883
P23528	Q8TE77	0	dephosphorylation	up-regulates activity	0.717	Differential activities, subcellular distribution and tissue expression patterns of three members of Slingshot family phosphatases that dephosphorylate cofilin.\|Cofilin, a key regulator of actin filament dynamics, is inactivated by phosphorylation at Ser-3 by LIM-kinases and is reactivated by dephosphorylation by a family of protein phosphatases, termed Slingshot (SSH).	SIGNOR-248759
Q13002	P17612	0	phosphorylation	up-regulates activity	0.2	GluR6 glutamate receptor, transiently expressed in mammalian cells, is directly phosphorylated by PKA, and that intracellularly applied PKA increases the amplitude of the glutamate response. Site-specific mutagenesis of the serine residue (Ser 684) representing a PKA consensus site completely eliminates PKA-mediated phosphorylation of this site as well as the potentiation of the glutamate response.	SIGNOR-250315
O60516	P42345	0	phosphorylation	up-regulates	0.358	While promoting initiation of protein translation through mtor, eukaryoticinitiation factor 4e, and the ribosomal p70-s6 kinase.	SIGNOR-122035
Q92934	P48454	0	dephosphorylation	up-regulates activity	0.399	Ca2+-induced apoptosis through calcineurin dephosphorylation of BAD\|Calcineurin was found to dephosphorylate BAD, a pro-apoptotic member of the Bcl-2 family, thus enhancing BAD heterodimerization with Bcl-xL and promoting apoptosis.	SIGNOR-248529
Q09472	Q13950	1	acetylation	up-regulates quantity	0.453	Bmp-induced non-smad erk signaling pathway cooperatively regulates osteoblast differentiation, in part, through increasing the stability and transcriptional activity of runx2 or increasing runx2 acetylation by p300.	SIGNOR-195579
P35222	P24385	1	transcriptional regulation	up-regulates quantity by expression	0.801	One of the most well studied activators of CCND1 transcription is β-catenin, which could be actived by AKT signalling to inducing G1/S transition. When β-catenin is translocated from the cytoplasm to the nucleus, it forms a complex with the ternary complex factor (TCF) and/or lymphoid enhancer-binding factor (LEF) and stimulates cyclin D1 gene transcription (Fig. 4C).In agreement with the data described above, a chromatin immunoprecipitation (ChIP) assay confirmed that TNC regulates the binding of β-catenin to the TCF/LEF-binding site in the CCND1 promoter (Fig. 4C). Additionally, the β-cateninbinding activity with respect to the CCND1 promoter was much higher in TNC-overexpression PANC-1 cells than in the vector controls.	SIGNOR-277738
Q5S007	Q9UJV3	0	ubiquitination	down-regulates quantity by destabilization	0.2	The E3 ligase TRIM1 ubiquitinates LRRK2 and controls its localization, degradation, and toxicity.	SIGNOR-278763
Q16566	Q9UQL6	1	phosphorylation	down-regulates	0.51	Recently, camkiv, a calcium-calmodulindependent protein kinase, was also shown to activate mef2s by dissociating class ii histone deacetylases (e.g., Hdac5) from mef2s, thus relieving the transcriptional repressive effect of hdacs.	SIGNOR-236571
Q8IZP0	P28482	0	phosphorylation	up-regulates	0.445	Our mass spectrometry also identified abi1 s183 and s225 on abi1 (numbering corresponds to abi1 isoform 1) as sites phosphorylated on endogenous protein and in the wildtype erk-dependent in vitro phosphorylated sample. these data indicate erk phosphorylation of abi1 is required for basal and egf-induced wrc interaction with the wrp2/3 complex.	SIGNOR-172873
O95819	Q16584	1	phosphorylation	up-regulates activity	0.304	The MAP4K4 and MLK3 associates with each other, and MAP4K4 phosphorylates MLK3 on Thr738 and increases MLK3 kinase activity and downstream signaling.	SIGNOR-277571
P42768	P08631	0	phosphorylation	up-regulates activity	0.555	Hck induces tyrosine phosphorylation of WASp. Here we show that the Src family kinase Hck induces phosphorylation of WASp-Tyr(291) independently of Cdc42 and that this causes a shift in the mobility of WASp upon SDS-PAGE. A phospho-mimicking mutant, WASp-Y291E, exhibited an enhanced ability to stimulate actin polymerization in a cell-free system and when microinjected into primary macrophages induced extensive filopodium formation with greater efficiency than wild-type WASp or a Y291F mutant. We propose that phosphorylation of Tyr(291) directly regulates WASp function.	SIGNOR-273957
Q6VAB6	P16298	0	dephosphorylation	up-regulates activity	0.259	These findings indicate that calcineurin modulates the phosphorylation state of KSR2, but not KSR1, and identifies S198, T287, and the S310 14-3-3 binding site as the KSR2 residues targeted by calcineurin.\|the negative regulators 14-3-3	SIGNOR-248381
Q9UN19	P07948	0	phosphorylation	up-regulates activity	0.625	Src family kinases mediate receptor-stimulated, phosphoinositide 3-kinase-dependent, tyrosine phosphorylation of dual adaptor for phosphotyrosine and 3-phosphoinositides-1 in endothelial and B cell lines\|yrosine phosphorylation of DAPP-1 appears important for appropriate intracellular targeting and creates a potential binding site for Src homology 2 domain-containing proteins.	SIGNOR-249378
O75582	P68431	1	phosphorylation	down-regulates activity	0.2	Phosphorylation at ser-11 (h3s10ph) by rps6ka4 and rps6ka5 is important during interphase because it enables the transcription of genes following external stimulation, like mitogens, stress, growth factors or uv irradiation and result in the activation of genes, such as c-fos and c-jun.	SIGNOR-138483
P68400	P13349	1	phosphorylation	up-regulates activity	0.307	Here, we report that Myf-5 protein constitutes a substrate for phosphorylation in vitro by protein kinase CK2. We identified two potential phosphorylation sites at serine49 and serine133, both of which seem to be necessary for Myf-5 activity.	SIGNOR-250922
Q93045	P53779	0	phosphorylation	down-regulates	0.444	We demonstrate that purified scg10 can be phosphorylated by two subclasses of mitogen-activated protein (map) kinases, c-jun n-terminal/stress-activated protein kinase (jnk/sapk) and p38 map kinase;jnk3/sapkbeta phosphorylation occurs at ser-62 and ser-73, residues that result in reduced microtubule-destabilizing activity for scg10.	SIGNOR-112114
P01375	Q00839	0	post transcriptional regulation	up-regulates quantity by stabilization	0.2	In the present study, we show that hnRNP-U specifically enhances the expression of tumor necrosis factor alpha mRNA by increasing its stability, possibly through binding to the 3' untranslated region. We also show that hnRNP-U enhances the expression of several other genes as well, including GADD45A, HEXIM1, HOXA2, IER3, NHLH2, and ZFY, by binding to and stabilizing these mRNAs.	SIGNOR-262281
Q13464	P08670	1	phosphorylation	down-regulates activity	0.367	We found that vimentin, the most widely expressed intermediate filament protein, served as an excellent substrate for Rho-associated kinase (Rho-kinase) and that vimentin phosphorylated by Rho-kinase lost its ability to form filaments in vitro. Two amino-terminal sites on vimentin, Ser38 and Ser71, were identified as the major phosphorylation sites for Rho-kinase, and Ser71 was the most favored and unique phosphorylation site for Rho-kinase in vitro.	SIGNOR-248998
O96013	P03372	1	phosphorylation	up-regulates activity	0.277	Further, PAK4 phosphorylated ER\u03b1-Ser305, a phosphorylation event needed for the PAK4 activation of ER\u03b1-dependent transcription.\|Further, PAK4 phosphorylated ERalpha-Ser305, a phosphorylation event needed for the PAK4 activation of ERalpha dependent transcription.	SIGNOR-279472
Q93008	Q13485	1	deubiquitination	up-regulates	0.648	Smad4 is monoubiquitinated in lysine 519 in vivo, a modification that inhibits smad4 by impeding association with phospho-smad2. Fam reverts this negative modification, re-empowering smad4 function;control of smad4 is a good way to regulate bone formation. Fam and ectodermin/tif1gamma (ecto) were reported to respectively regulate the de-ubiquitination and ubiquitination of smad4.	SIGNOR-236855
P12931	Q9UHR4	1	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
O00141	O15111	1	phosphorylation	up-regulates activity	0.26	SGK1 directly phosphorylates IKKalpha at Thr 23 and indirectly activates IKKalpha at Ser 180.\|SGK1 directly phosphorylates IKKalpha at Thr-23 and indirectly activates IKKalpha at Ser-180.	SIGNOR-278987
Q15139	P63167	1	phosphorylation	down-regulates activity	0.2	We now provide evidence that PKD phosphorylates an additional site in DLC1, namely serine 807 within the GAP domain, adding another layer of complexity to PKD-mediated negative regulation of the DLC1 tumor suppressor protein.\|We previously reported that PKD inhibits DLC1 cellular function through phosphorylation of serines 327 and 431 [10].	SIGNOR-279265
P46937	Q05397	0	phosphorylation	up-regulates activity	0.284	Then, FAK phosphorylates and activates YAP, leading to the activation and nuclear translocation of YAP/TAZ transcription factor, which is known to be involved in such cellular mechanoresponses [ xref , xref ].	SIGNOR-280099
P36969	Q16236	0	transcriptional regulation	up-regulates quantity by expression	0.383	NFE2L2 is stabilized and translocates to the nucleus, where it dimerizes with sMAF proteins. This complex binds to AREs to mediate the transcription of genes involved in iron metabolism, GSH metabolism, and ROS detoxification.GPX4 stands out within the GPX family due to its unique ability to reduce lipid hydroperoxides directly within cell membranes, thereby safeguarding cells from lipid peroxidation and ferroptosis.	SIGNOR-279874
P53350	Q08050	1	phosphorylation	up-regulates	0.705	It has been reported that plk1 could directly phosphorylate foxm1 at ser-715 and ser-724 for full activation and proper mitotic progression	SIGNOR-187892
P35222	Q9NQU5	0	phosphorylation	down-regulates quantity	0.2	Moreover, we find that \u03b2-catenin is also localized with PAK6 in cell-cell junctions and is a novel PAK6 substrate.\|PAK6 binds to and phosphorylates beta-catenin.	SIGNOR-279546
Q9GZM8	P28482	0	phosphorylation	up-regulates activity	0.287	In this case, only NudelS2 and NudelS5 were phosphorylated. Therefore, T219, S242, and T245 of Nudel were phosphorylation sites of Cdc2 in vitro. In contrast, Erk2 only phosphorylated T219 and T245. These two sites, with surrounding sequences such as PATP from residues 217 to 220 and PLTP from 243 to 246, respectively, are indeed typical MAPK sites	SIGNOR-274076
P17612	P10636	1	phosphorylation	down-regulates	0.433	However, other kinases, such as cdk5, p38 and pka, also phosphorylate tau at t231tau phosphorylation at t231, s235 and s262 also contributes to the dissociation of tau from microtubules	SIGNOR-171066
Q9UJV3	Q96R06	1	ubiquitination	down-regulates quantity by destabilization	0.309	These data indicated that Mid2 was ubiquitinating Astrin at K409 and targeting Astrin for degradation during cytokinesis.	SIGNOR-278549
Q13131	P49815	1	phosphorylation	up-regulates activity	0.682	However, AMP-activated protein kinase (AMPK), an essential cellular energy sensor, phosphorylates and activates TSC2 [ xref ].	SIGNOR-278981
Q05397	P46937	1	phosphorylation	up-regulates activity	0.284	Then, FAK phosphorylates and activates YAP, leading to the activation and nuclear translocation of YAP/TAZ transcription factor, which is known to be involved in such cellular mechanoresponses [ xref , xref ].	SIGNOR-280099
O75581	P48730	0	phosphorylation	up-regulates activity	0.2	Central to WNT signalosome formation is phosphorylation of LRP6 at multiple sites, with GSK3β phosphorylating LRP6 at S1490 and CK1 family members phosphorylating LRP6 at T1479 and T1493	SIGNOR-275402
Q02750	P00540	0	phosphorylation	up-regulates activity	0.485	Our data indicate that Mos activated MEK1 in vitro as well as in vivo by phosphorylating Ser 222.	SIGNOR-260920
O75150	Q13315	0	phosphorylation	up-regulates	0.443	E3 ubiquitin ligase, a heterodimeric complex of the ringfinger rfn20/rfn40 is phosphorylated by atm.	SIGNOR-175003
Q13315	O43504	1	phosphorylation	up-regulates activity	0.336	Strikingly, we found that the kinase ataxia telangiectasia mutated (ATM) phosphorylated HBXIP at Ser (108).\|The knockdown of ATM by siRNA remarkably decreased the levels of serine phosphorylation and blocked the nuclear import of HBXIP.	SIGNOR-279791
P29353	P43403	0	phosphorylation	up-regulates	0.677	The syk-family kinases (syk and zap-70) were able to phosphorylate the y239 and y240 sites, and less efficiently the y317 site on shc1 (iso2).	SIGNOR-59659
O15530	P08069	0	phosphorylation	up-regulates	0.341	Previous studies indicate that optimal activation of PDK1 requires phosphorylation of Tyr373/376 (11, 12, 14, 17), and growth factor receptor activation leads to PDK1 recruitment to the plasma membrane, followed by sequential phosphorylation of Tyr9 and then Tyr373/376	SIGNOR-166710
Q16539	Q9UBK2	1	phosphorylation	up-regulates	0.586	Cytokine stimulation of energy expenditure through p38 map kinase activation of ppargamma coactivator-1we show here that many cytokines activate the transcriptional ppar gamma coactivator-1 (pgc-1) through phosphorylation by p38 kinase, resulting in stabilization and activation of pgc-1 proteinp38 mapk directly phosphorylates pgc-1 on residues threonine 262, serine 265, and threonine 298	SIGNOR-112774
P78352	Q9NZJ5	0	phosphorylation	up-regulates activity	0.268	To elucidate the molecular mechanism, we found that activated PERK phosphorylates CAMP response element binding protein (CREB) and PSD95 directly at the S129 and T19 residues, respectively.	SIGNOR-280004
P16885	P06241	0	phosphorylation	up-regulates activity	0.575	The phosphorylation of purified phospholipase C-gamma 1 (PLC-gamma 1) and PLC-gamma 2 by src-family-protein tyrosine kinases (PTKs) P56lck, p53/56lyn, p59hck, p59fyn, and p60src was studied in vitro. All five PTKs phosphorylated PLC-gamma 1 and PLC-gamma 2, suggesting that both PLC-gamma isozymes can be phosphorylated in cells by any of the src-family PTKs in response to the activation of cell surface receptors.	SIGNOR-249340
Q9Y281	Q15569	0	phosphorylation	down-regulates activity	0.321	Like TESK1, TESK2 phosphorylated cofilin specifically at Ser-3 and induced formation of actin stress fibers and focal adhesionsExpression of cofilin or S3A-cofilin into HeLa cells induced marked decreases in rhodamine-phalloidin staining due to the actin binding and -depolymerizing activity of cofilin	SIGNOR-246719
P23769	P01222	1	transcriptional regulation	up-regulates quantity by expression	0.39	Pit-1, is necessary but not sufficient to allow basal transcription of the mTSHβ gene.The analysis of the mTSHβ gene described in this report provides evidence for the participation of a zinc finger factor, GATA-2, with a POU homeodomain partner, Pit-1, on a such a composite element.In summary, we have shown the requirement for at least two different classes of transcription factors to regulate mTSHβ gene expression. Both GATA-2 and Pit-1 can bind independently to the P1 region of the promoter, form a heteromeric complex with DNA, and functionally synergize to activate TSHβ promoter activity.	SIGNOR-267253
P11309	Q99683	1	phosphorylation	down-regulates	0.28	Pim1 phosphorylates and negatively regulates ask1-mediated apoptosispim1 phosphorylation of ask1 on ser83 inhibited ask1-mediated c-jun n-terminal kinase phosphorylation	SIGNOR-187905
Q13315	Q14738	1	phosphorylation	up-regulates activity	0.297	In the present study, we demonstrate that ataxia-telangiectasia mutated (ATM) directly phosphorylates and specifically regulates B56γ3, B56γ2 and B56δ, after DNA damage. We further show that phosphorylation of B56γ3 at Ser510 leads to an increase in B56γ3-PP2A complexes, and direction of PP2A phosphatase activity toward the substrate p53, activating its tumor-suppressive functions. we show that Ser510 phosphorylation significantly enhances the ability of B56γ3 to inhibit cell proliferation and anchorage-independent growth.	SIGNOR-276319
O95382	Q16539	1	phosphorylation	up-regulates activity	0.2	These data indicate that MKK6 phosphorylates p38 MAP kinase on Thr-180 and Tyr-182, the sites of phosphorylation that activate p38 MAP kinase	SIGNOR-260916
P03186	Q9Y6K9	1	deubiquitination	down-regulates activity	0.2	In the current study, we have found that BPLF1 interferes with innate immune activation by targeting multiple intermediates along the TLR signal transduction pathway, including TRAF6, NEMO, and IκBα. BPLF1 can remove ubiquitin tags from proteins in the TLR signaling cascade. This inhibits TLR signaling and decreases the expression of immune response genes.	SIGNOR-266743
P08047	P24821	1	transcriptional regulation	up-regulates quantity by expression	0.2	Sp1 and Ets1 are potent transactivators of the TN-C promoter.	SIGNOR-261600
Q16581	P25098	0	phosphorylation	down-regulates activity	0.2	These findings indicated that agonist-induced C3aR phosphorylation by GRK2 promotes C3aR desensitization.	SIGNOR-279044
Q15811	Q96CN9	0	relocalization	up-regulates activity	0.2	GFP-GCC88 was immunoprecipitated by both the short and long form of ITSN-1 but not with FLAG-Rheb (Figure 4A). These data demonstrate that both GCC88 and ITSN-1 are part of a complex. 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-260600
Q96T23	P53350	0	phosphorylation	up-regulates activity	0.352	Moreover, CDK1 phosphorylates RSF1 at Ser1375, and this phosphorylation is necessary for PLK1 recruitment. Subsequently, PLK1 phosphorylates RSF1 at Ser1359, stabilizing PLK1 deposition.	SIGNOR-273590
P16284	P06239	0	phosphorylation	up-regulates activity	0.588	We demonstrated that phosphorylation of PECAM-1 by Src or Csk family kinases was sufficient to trigger its association with SHP-2. Moreover, it was able to promote binding of PECAM-1 to SHP-1, a SHP-2-related protein-tyrosine phosphatase expressed in hemopoietic cells. Taken together, these findings indicated that the Src and Csk families of kinases are strong candidates for mediating tyrosine phosphorylation of PECAM-1 and triggering its association with SH2 domain-containing phosphatases under physiological circumstances.	SIGNOR-262742
Q15831	Q14680	1	phosphorylation	up-regulates	0.2	Site-directed mutagenesis indicated that thr167 and ser171, located between the dfg and ape motifs in the activation loop or t-loop, need to be autophosphorylated for melk to be active as a protein kinase (fig. 5). These sites are conserved in all other ampk-related protein kinases (fig. 4a), and the site corresponding to thr167 has been shown to be phosphorylated by protein kinase lkb1 (5).	SIGNOR-141038
P51955	Q5FBB7	1	phosphorylation	up-regulates	0.2	Here we show that nek2a phosphorylates human sgo1 and such phosphorylation is essential for faithful chromosome congression in mitosis. phosphorylation sites were mapped to ser(14) and ser(507)	SIGNOR-156882
P53350	O94901	1	phosphorylation	down-regulates activity	0.453	Here, we show that SUN1, located in the INM, undergoes mitosis-specific phosphorylation on at least 3 sites within its nucleoplasmic N-terminus. We further identify Cdk1 as the kinase responsible for serine 48 and 333 phosphorylation, while serine 138 is phosphorylated by Plk1. Together, these data support a model whereby mitotic phosphorylation of SUN1 disrupts interactions with nucleoplasmic binding partners, promoting disassembly of the nuclear lamina and, potentially, its chromatin interactions.	SIGNOR-263098
Q9Y478	Q13586	1	phosphorylation	down-regulates activity	0.2	STIM1 is a novel exercise‐regulated AMPK substrate. Phosphorylation of STIM1 by AMPK suppresses SOCE	SIGNOR-277298
Q9UHI6	P41162	0	transcriptional regulation	down-regulates quantity by repression	0.739	ETV3 target genes including etv3, ddx20, and dusp6 provide negative feedback regulation of ETV3 production and activity. Negative feedback along with constitutive instability may serve to tightly regulate ETV3 abundance. Our date suggest that phosphorylation by ERK2 relieves repression by ETV3, allowing activation of cell cycle control genes including myc, components of the NF-κB pathway, and genes required form RNA processing and translation.	SIGNOR-262779
O75592	P10275	1	ubiquitination	down-regulates quantity by destabilization	0.2	We identified several E3 ligases as strong candidates responsible for AR and MYC protein loss as HECTD4, MYCBP2, and TRIM49. HECTD4 and MYCBP2 target AR and MYC for degradation while TRIM49 appears to promote AR and MYC stability. We have shown that these E3 ligases in turn are directly regulated by MYC. MYC in turn represses the expression of ubiquitin ligases, HECTD4 and MYCBP2 that promote AR and MYC protein degradation, further suppressing MYC and AR in a feed forward loop.	SIGNOR-267149
P04150	Q13886	1	transcriptional regulation	up-regulates quantity by expression	0.321	We show that in addition, DEX-bound GR directly promotes the expression of adipogenic TFs, including C/EBPβ, Klf5, Klf9, and C/EBPα	SIGNOR-256119
O15550	P68431	1	demethylation	down-regulates activity	0.2	Ubiquitously Transcribed Tetratricopeptide Repeat on chromosome X (UTX) and Jumonji D3 (JMJD3) as novel histone demethylases that catalyze the removal of di- and trimethyl groups on histone H3 lysine 27, thereby promoting target gene activation.	SIGNOR-260017
O60814	Q14493	0	translation regulation	up-regulates quantity by expression	0.2	Synthesis of mature histone mRNA requires only a single processing reaction: an endonucleolytic cleavage between a conserved stem-loop and a purine-rich downstream element to form the 3' end. The stem-loop binding protein (SLBP) is required for processing, and following processing, histone mRNA is transported to the cytoplasm, where SLBP participates in translation of the histone mRNA\|We used radiolabeled probes generated by PCR targeting the open reading frame (ORF) to detect histones H2A, H2B, H3, H4, and H1 and used 7SK snRNA as a loading control (Fig. 2A). The abundance of histone H2A, H2B, H3, and H4 mRNAs is reduced to 37% to 70% of control levels in the SLBP knockdown cells when compared to the C2 control.	SIGNOR-265383
Q9UPN9	P35222	1	ubiquitination	down-regulates quantity by destabilization	0.457	TRIM33 ubiquitylates nuclear beta-catenin.\|Tumour suppressor TRIM33 targets nuclear beta-catenin degradation.	SIGNOR-278578
Q96PE2	P33981	0	phosphorylation	down-regulates activity	0.2	Because Mps1 also phosphorylates ARHGEF17, the Mps1\u2013ARHGEF17 complex is short lived and promotes its own dissociation, which in turn releases Mps1 and ARHGEF17 from the kinetochore.\|ARHGEF17 and Mps1 interact during mitosis and Mps1 phosphorylates ARHGEF17.	SIGNOR-279352

O00308

P60484

1

ubiquitination

down-regulates quantity by destabilization

0.632

We have shown that WWP2 interacts with and ubiquitylates PTEN, promoting its degradation.

SIGNOR-278650

Q14676

P68400

0

phosphorylation

up-regulates

0.346

The mdc1-nbs1 interaction occurs through a specific region (residues 200-420) of mdc1, which contains multiple consensus casein kinase 2 (ck2) phosphorylation sites.

SIGNOR-179887

P49757

Q2M2I8

0

phosphorylation

up-regulates

0.459

Collectively, these observations demonstrate that numb endocytic activity is regulated by aak1 and that phosphorylation may be a critical step in promoting coated pit maturation.

SIGNOR-179606

P25490

P53350

0

phosphorylation

up-regulates

0.392

More recently, we identified and mapped multiple phosphorylation sites in yy1, including, threonine 39, serine 118, serine 247, threonine 348 and threonine 378. The first kinase proven to phosphorylate yy1 in vivo was plk1, which phosphorylates threonine 39 during g2/m stage of the cell cycle [25]. Ck2_ is another kinase identified as constitutively phosphorylating yy1 at serine 118. This modification protects yy1 cleavage by caspase 7 during apoptosis

SIGNOR-200087

P28482

Q05682

1

phosphorylation

down-regulates

0.539

Extracellular signal-regulated kinases (erks) phosphorylate the high molecular mass isoform of the actin-binding protein caldesmon (h-cad) at two sites (ser(759) and ser(789)) during smooth muscle stimulation. Nmr spectroscopy shows that the actin binding properties of the minimal inhibitory region of caldesmon, residues 750-779, alter upon map kinase phosphorylation of ser-759, a residue not involved in actin binding. This phosphorylation leads to markedly diminished actin affinity as a result of the loss of interaction at one of the two sites that bind to f-actin.

SIGNOR-71037

Q15078

Q9H0K1

0

phosphorylation

down-regulates

0.331

Sik2 phosphorylates p35 at ser 91, to trigger its ubiquitylation by pja2 and promote insulin secretion. _-cell knockout of sik2 leads to accumulation of p35 and impaired secretion

SIGNOR-204648

Q13115

P27361

1

dephosphorylation

down-regulates activity

0.709

Dephosphorylation and Inactivation of ERKs|ERK1 phosphorylated on either threonine (ERK1*Y204F) or tyrosine alone (ERK1*T202A) was utilized as a substrate for HVH2. Threonine 202 and tyrosine 204 in ERK1 (53) correspond to threonine 183 and tyrosine 185 in ERK2 which are the activation-phosphorylation sites by MEK(14, 15, 16). ERK1*, a kinase-deficient mutant, was phosphorylated on both threonine and tyrosine by MEK2 (Fig. 3B). ERK1*T202A, having threonine 202 substituted by an alanine, was phosphorylated only on tyrosine while ERK1*Y204F, having tyrosine 204 substituted by a phenylalanine, was phosphorylated only on threonine (Fig. 3B). GST-HVH2 dephosphorylated all three ERK1* mutants (Fig. 3A), suggesting that double phosphorylations of adjacent threonine and tyrosine were not a prerequisite for HVH2 recognition. However, HVH2 dephosphorylated ERK1* and ERK1*T202A more efficiently than ERK1*Y204F (Fig. 3A), indicating that HVH2 preferred phosphotyrosine over phosphothreonine. Interestingly, MEK also phosphorylated tyrosine residues more efficiently than threonine residues of ERK

SIGNOR-248716

Q00987

Q13761

1

ubiquitination

down-regulates quantity by destabilization

0.579

RUNX3 protein is ubiquitinated by MDM2 at Lys-94 and Lys-148.|RUNX3 protein is ubiquitinated by MDM2 at Lys 94 and Lys 148.|MDM2 suppresses the transcriptional activity of RUNX3.

SIGNOR-278557

Q9UGP5

Q7Z6Z7

0

polyubiquitination

down-regulates quantity by destabilization

0.309

We found that Pol λ can be ubiquitinated by the E3 ligase Mule in vitro and in vivo and that this interaction is functionally connected to the phosphorylation-dependent stabilization of Pol λ by Cdk2/cyclinA.

SIGNOR-272904

P35222

Q5VWQ8

0

relocalization

down-regulates quantity

0.299

DAB2IP prevents β-catenin nuclear translocation.

SIGNOR-254755

Q8N726

Q14669

0

ubiquitination

down-regulates quantity by destabilization

0.582

ULF interacts with ARF both in vitro and in vivo and promotes the lysine-independent ubiquitylation and degradation of ARF.

SIGNOR-266781

P10070

Q9Y297

0

ubiquitination

down-regulates quantity by destabilization

0.651

The phosphorylated gli2 protein interacts with beta-trcp, and is ubiquitinated and degraded by the proteasome

SIGNOR-146109

Q15759

P30281

1

phosphorylation

down-regulates quantity by destabilization

0.2

P38SAPK2 phosphorylates cyclin D3 at Thr-283 and targets it for proteasomal degradation.

SIGNOR-280023

Q86U70

Q9NVW2

0

polyubiquitination

down-regulates quantity by destabilization

0.566

Here we identify RLIM as a ubiquitin protein ligase that is able to target CLIM cofactors for degradation through the 26S proteasome pathway.

SIGNOR-272617

O43318

Q15797

1

phosphorylation

up-regulates activity

0.373

This analysis showed that phosphorylation of Smad1 at the C-terminal serines S463 and S465 was increased by co-expression of constitutively active TAK1.

SIGNOR-279419

Q15910

P49841

0

phosphorylation

down-regulates activity

0.33

GSK3beta phosphorylates EZH2 at Ser363 and Thr367 in vitro, and activating GSK3beta upregulates Thr367 phosphorylationin vivo.

SIGNOR-278176

Q13085

Q13131

0

phosphorylation

down-regulates activity

0.7

We have isolated and purified from rat livers a novel kinase that phosphorylates and inactivates the carboxylase Ser1200 isphosphorylated by both CAMP-dependent protein kinase and AMP-activated protein kinase

SIGNOR-250400

Q7L591

P07948

0

phosphorylation

up-regulates activity

0.409

An adaptor protein Dok-3 mediates the suppressive function of LYN. The Dok-3 phosphorylated by LYN upon BCR stimulation forms a complex with GRB2, which allows it to enter into the signalosome and associate with activation of SHIP protein. This translocation facilitates the efficient inhibition of PLCc2 and SYK from activation, subsequently resulting in the suppression of downstream Ca2+ signaling.

SIGNOR-268447

P50281

Q13443

1

cleavage

down-regulates quantity by destabilization

0.341

Here we show that MT1-MMP forms a complex with FGFR2 and ADAM9 in osteoblasts and proteolytically inactivates ADAM9|Western blotting using antibodies against ectodomain of ADAM9 detected a fragment (around 26 kDa) of ADAM9 in the conditioned culture medium from cells cotransfected with wild-type MT1-MMP, but not in that with catalytic activity-dead MT1-MMP (Figure 6A, top).

SIGNOR-260301

P02511

Q92481

0

transcriptional regulation

up-regulates quantity by expression

0.2

Aberrant expression of CRYAB has been shown to be associated with several neurological diseases and malignant neoplasms. To identify transcriptional regulators of CRYAB expression, we examined its promoter for binding sites of transcription factors and identified four potential AP-2 binding sites in addition to a p53 binding site reported previously|Taken together, our results indicate that AP-2_ up-regulates the transcription of the CRYAB gene through stabilizing p53

SIGNOR-253637

P06239

P20138

1

phosphorylation

up-regulates

0.271

Human cd33 has two tyrosine residues in its cytoplasmic domain (y340 and y358). When phosphorylated, these tyrosines could function as docking sites for the phosphatases, shp-1 and/or shp-2, enabling cd33 to function as an inhibitory receptor. Lck is effective at phosphorylating y340

SIGNOR-78960

P11309

Q04206

1

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

O15392

Q8IWT3

0

ubiquitination

down-regulates quantity

0.489

CUL9 promotes the ubiquitylation and degradation of survivin and is inhibited by CUL7.|Together, these results demonstrate the specificity of survivin ubiquitylation by CUL9 E3 ligase complex.

SIGNOR-278808

Q15796

Q96PU5

0

ubiquitination

down-regulates activity

0.781

Through its ww domain, nedd4l specifically recognizes a tgf-beta-induced phosphothr-protyr motif in the linker region, resulting in smad2/3 polyubiquitination and degradation

SIGNOR-217622

P19174

Q16620

0

phosphorylation

up-regulates activity

0.647

Both Shc and PLCgamma1 are phosphorylated by TrkB, thereby initiating Shc/Ras/MAP kinase and PLCgamma1 signaling respectively.|We conclude that activation of pY783 PLCgamma1 is due mainly to TrkB activation in these models and that TrkB induced PLCgamma1 signaling promotes limbic epileptogenesis.

SIGNOR-279241

O75531

P60510

0

dephosphorylation

up-regulates

0.2

Herein, we demonstrate we demonstrate that phosphorylation of ser4 and/or thr2/thr3 abrogates the interaction of baf with dna and reduces its interaction with the lem domain. We have identified the major phosphatase responsible for dephosphorylation of ser-4 to be protein phosphatase 4 catalytic subunit.

SIGNOR-203281

Q13263

Q05655

0

phosphorylation

down-regulates

0.2

This work demonstrates that tif1beta is phosphorylated on ser473, the alteration of which is dynamically associated with cell cycle progression and functionally linked to transcriptional regulation. Phosphorylation of tif1beta/ser473 is mediated by the pkcdelta pathway and is closely linked to cell proliferation. Phosphorylation of tif1beta/ser473 coincides with the induction of cell cycle gene cyclin a2 at the s-phase. Promoter of cyclin a2 gene is occupied by tif1beta and such occupancy is inversely correlated with ser473 phosphorylation. Non-phosphorylated tif1beta/ser473 allowed greater tif1beta association with the regulatory regions and the consequent repression of these genes.

SIGNOR-179250

P17612

P12931

1

phosphorylation

up-regulates activity

0.361

PKA activated Src both in vitro and in vivo by phosphorylating Src on serine 17 within its amino terminus

SIGNOR-247988

Q13485

P49841

0

phosphorylation

down-regulates quantity by destabilization

0.398

In the presence of FGF, Wnt potentiates TGF-β signaling by preventing Smad4 GSK3 phosphorylations that inhibit a transcriptional activation domain located in the linker region.

SIGNOR-276440

P08151

Q96J02

0

ubiquitination

down-regulates

0.578

The consequent activation of_ itch, together with the recruitment of gli1 through direct binding with_ numb, allows gli1 to enter into the complex, resulting in gli1 ubiquitination and degradation. we demonstrate that the hedgehog transcription factor gli1 is targeted by numb for itch-dependent ubiquitination, which suppresses hedgehog signals, thus arresting growth and promoting cell differentiation

SIGNOR-150847

Q13043

O43561

1

phosphorylation

up-regulates activity

0.2

MST kinase phosphorylates and activates LATS kinase.

SIGNOR-279661

Q9NWQ8

P06241

0

phosphorylation

up-regulates activity

0.703

Thus, Fyn mediates Csk-binding protein-Csk interaction and recruits Csk to rafts by phosphorylating Csk-binding protein.

SIGNOR-279987

P08246

P55085

1

cleavage

down-regulates activity

0.395

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

SIGNOR-263588

P63000

Q13459

0

gtpase-activating protein

down-regulates activity

0.541

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-260510

Q9H0B6

Q13131

0

phosphorylation

up-regulates

0.2

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

SIGNOR-174681

P01106

P15884

0

transcriptional regulation

up-regulates quantity by expression

0.371

Association of c-Jun, β-catenin, and TCF4 specifically with the downstream enhancer underlies mitogen stimulation of c-Myc transcription.

SIGNOR-253324

P28482

P49795

1

phosphorylation

up-regulates

0.474

Phosphorylation of gaip by erk2 were abrogated when serine at position 151 in the rgs domain was substituted by an alanine residue using site-directed mutagenesis. Furthermore, the lysosomal-autophagic pathway was not stimulated in s151a-gaip mutant-expressing cells when compared with wild-type gaip-expressing cells. These results demonstrate that the gtpase-activating protein activity of gaip is stimulated by erk2 phosphorylation.

SIGNOR-129883

P23528

Q8TE77

0

dephosphorylation

up-regulates activity

0.717

Differential activities, subcellular distribution and tissue expression patterns of three members of Slingshot family phosphatases that dephosphorylate cofilin.|Cofilin, a key regulator of actin filament dynamics, is inactivated by phosphorylation at Ser-3 by LIM-kinases and is reactivated by dephosphorylation by a family of protein phosphatases, termed Slingshot (SSH).

SIGNOR-248759

Q13002

P17612

0

phosphorylation

up-regulates activity

0.2

GluR6 glutamate receptor, transiently expressed in mammalian cells, is directly phosphorylated by PKA, and that intracellularly applied PKA increases the amplitude of the glutamate response. Site-specific mutagenesis of the serine residue (Ser 684) representing a PKA consensus site completely eliminates PKA-mediated phosphorylation of this site as well as the potentiation of the glutamate response.

SIGNOR-250315

O60516

P42345

0

phosphorylation

up-regulates

0.358

While promoting initiation of protein translation through mtor, eukaryoticinitiation factor 4e, and the ribosomal p70-s6 kinase.

SIGNOR-122035

Q92934

P48454

0

dephosphorylation

up-regulates activity

0.399

Ca2+-induced apoptosis through calcineurin dephosphorylation of BAD|Calcineurin was found to dephosphorylate BAD, a pro-apoptotic member of the Bcl-2 family, thus enhancing BAD heterodimerization with Bcl-xL and promoting apoptosis.

SIGNOR-248529

Q09472

Q13950

1

acetylation

up-regulates quantity

0.453

Bmp-induced non-smad erk signaling pathway cooperatively regulates osteoblast differentiation, in part, through increasing the stability and transcriptional activity of runx2 or increasing runx2 acetylation by p300.

SIGNOR-195579

P35222

P24385

1

transcriptional regulation

up-regulates quantity by expression

0.801

One of the most well studied activators of CCND1 transcription is β-catenin, which could be actived by AKT signalling to inducing G1/S transition. When β-catenin is translocated from the cytoplasm to the nucleus, it forms a complex with the ternary complex factor (TCF) and/or lymphoid enhancer-binding factor (LEF) and stimulates cyclin D1 gene transcription (Fig. 4C).In agreement with the data described above, a chromatin immunoprecipitation (ChIP) assay confirmed that TNC regulates the binding of β-catenin to the TCF/LEF-binding site in the CCND1 promoter (Fig. 4C). Additionally, the β-cateninbinding activity with respect to the CCND1 promoter was much higher in TNC-overexpression PANC-1 cells than in the vector controls.

SIGNOR-277738

Q5S007

Q9UJV3

0

ubiquitination

down-regulates quantity by destabilization

0.2

The E3 ligase TRIM1 ubiquitinates LRRK2 and controls its localization, degradation, and toxicity.

SIGNOR-278763

Q16566

Q9UQL6

1

phosphorylation

down-regulates

0.51

Recently, camkiv, a calcium-calmodulindependent protein kinase, was also shown to activate mef2s by dissociating class ii histone deacetylases (e.g., Hdac5) from mef2s, thus relieving the transcriptional repressive effect of hdacs.

SIGNOR-236571

Q8IZP0

P28482

0

phosphorylation

up-regulates

0.445

Our mass spectrometry also identified abi1 s183 and s225 on abi1 (numbering corresponds to abi1 isoform 1) as sites phosphorylated on endogenous protein and in the wildtype erk-dependent in vitro phosphorylated sample. these data indicate erk phosphorylation of abi1 is required for basal and egf-induced wrc interaction with the wrp2/3 complex.

SIGNOR-172873

O95819

Q16584

1

phosphorylation

up-regulates activity

0.304

The MAP4K4 and MLK3 associates with each other, and MAP4K4 phosphorylates MLK3 on Thr738 and increases MLK3 kinase activity and downstream signaling.

SIGNOR-277571

P42768

P08631

0

phosphorylation

up-regulates activity

0.555

Hck induces tyrosine phosphorylation of WASp. Here we show that the Src family kinase Hck induces phosphorylation of WASp-Tyr(291) independently of Cdc42 and that this causes a shift in the mobility of WASp upon SDS-PAGE. A phospho-mimicking mutant, WASp-Y291E, exhibited an enhanced ability to stimulate actin polymerization in a cell-free system and when microinjected into primary macrophages induced extensive filopodium formation with greater efficiency than wild-type WASp or a Y291F mutant. We propose that phosphorylation of Tyr(291) directly regulates WASp function.

SIGNOR-273957

Q6VAB6

P16298

0

dephosphorylation

up-regulates activity

0.259

These findings indicate that calcineurin modulates the phosphorylation state of KSR2, but not KSR1, and identifies S198, T287, and the S310 14-3-3 binding site as the KSR2 residues targeted by calcineurin.|the negative regulators 14-3-3

SIGNOR-248381

Q9UN19

P07948

0

phosphorylation

up-regulates activity

0.625

Src family kinases mediate receptor-stimulated, phosphoinositide 3-kinase-dependent, tyrosine phosphorylation of dual adaptor for phosphotyrosine and 3-phosphoinositides-1 in endothelial and B cell lines|yrosine phosphorylation of DAPP-1 appears important for appropriate intracellular targeting and creates a potential binding site for Src homology 2 domain-containing proteins.

SIGNOR-249378

O75582

P68431

1

phosphorylation

down-regulates activity

0.2

Phosphorylation at ser-11 (h3s10ph) by rps6ka4 and rps6ka5 is important during interphase because it enables the transcription of genes following external stimulation, like mitogens, stress, growth factors or uv irradiation and result in the activation of genes, such as c-fos and c-jun.

SIGNOR-138483

P68400

P13349

1

phosphorylation

up-regulates activity

0.307

Here, we report that Myf-5 protein constitutes a substrate for phosphorylation in vitro by protein kinase CK2. We identified two potential phosphorylation sites at serine49 and serine133, both of which seem to be necessary for Myf-5 activity.

SIGNOR-250922

Q93045

P53779

0

phosphorylation

down-regulates

0.444

We demonstrate that purified scg10 can be phosphorylated by two subclasses of mitogen-activated protein (map) kinases, c-jun n-terminal/stress-activated protein kinase (jnk/sapk) and p38 map kinase;jnk3/sapkbeta phosphorylation occurs at ser-62 and ser-73, residues that result in reduced microtubule-destabilizing activity for scg10.

SIGNOR-112114

P01375

Q00839

0

post transcriptional regulation

up-regulates quantity by stabilization

0.2

In the present study, we show that hnRNP-U specifically enhances the expression of tumor necrosis factor alpha mRNA by increasing its stability, possibly through binding to the 3' untranslated region. We also show that hnRNP-U enhances the expression of several other genes as well, including GADD45A, HEXIM1, HOXA2, IER3, NHLH2, and ZFY, by binding to and stabilizing these mRNAs.

SIGNOR-262281

Q13464

P08670

1

phosphorylation

down-regulates activity

0.367

We found that vimentin, the most widely expressed intermediate filament protein, served as an excellent substrate for Rho-associated kinase (Rho-kinase) and that vimentin phosphorylated by Rho-kinase lost its ability to form filaments in vitro. Two amino-terminal sites on vimentin, Ser38 and Ser71, were identified as the major phosphorylation sites for Rho-kinase, and Ser71 was the most favored and unique phosphorylation site for Rho-kinase in vitro.

SIGNOR-248998

O96013

P03372

1

phosphorylation

up-regulates activity

0.277

Further, PAK4 phosphorylated ER\u03b1-Ser305, a phosphorylation event needed for the PAK4 activation of ER\u03b1-dependent transcription.|Further, PAK4 phosphorylated ERalpha-Ser305, a phosphorylation event needed for the PAK4 activation of ERalpha dependent transcription.

SIGNOR-279472

Q93008

Q13485

1

deubiquitination

up-regulates

0.648

Smad4 is monoubiquitinated in lysine 519 in vivo, a modification that inhibits smad4 by impeding association with phospho-smad2. Fam reverts this negative modification, re-empowering smad4 function;control of smad4 is a good way to regulate bone formation. Fam and ectodermin/tif1gamma (ecto) were reported to respectively regulate the de-ubiquitination and ubiquitination of smad4.

SIGNOR-236855

P12931

Q9UHR4

1

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

O00141

O15111

1

phosphorylation

up-regulates activity

0.26

SGK1 directly phosphorylates IKKalpha at Thr 23 and indirectly activates IKKalpha at Ser 180.|SGK1 directly phosphorylates IKKalpha at Thr-23 and indirectly activates IKKalpha at Ser-180.

SIGNOR-278987

Q15139

P63167

1

phosphorylation

down-regulates activity

0.2

We now provide evidence that PKD phosphorylates an additional site in DLC1, namely serine 807 within the GAP domain, adding another layer of complexity to PKD-mediated negative regulation of the DLC1 tumor suppressor protein.|We previously reported that PKD inhibits DLC1 cellular function through phosphorylation of serines 327 and 431 [10].

SIGNOR-279265

P46937

Q05397

0

phosphorylation

up-regulates activity

0.284

Then, FAK phosphorylates and activates YAP, leading to the activation and nuclear translocation of YAP/TAZ transcription factor, which is known to be involved in such cellular mechanoresponses [ xref , xref ].

SIGNOR-280099

P36969

Q16236

0

transcriptional regulation

up-regulates quantity by expression

0.383

NFE2L2 is stabilized and translocates to the nucleus, where it dimerizes with sMAF proteins. This complex binds to AREs to mediate the transcription of genes involved in iron metabolism, GSH metabolism, and ROS detoxification.GPX4 stands out within the GPX family due to its unique ability to reduce lipid hydroperoxides directly within cell membranes, thereby safeguarding cells from lipid peroxidation and ferroptosis.

SIGNOR-279874

P53350

Q08050

1

phosphorylation

up-regulates

0.705

It has been reported that plk1 could directly phosphorylate foxm1 at ser-715 and ser-724 for full activation and proper mitotic progression

SIGNOR-187892

P35222

Q9NQU5

0

phosphorylation

down-regulates quantity

0.2

Moreover, we find that \u03b2-catenin is also localized with PAK6 in cell-cell junctions and is a novel PAK6 substrate.|PAK6 binds to and phosphorylates beta-catenin.

SIGNOR-279546

Q9GZM8

P28482

0

phosphorylation

up-regulates activity

0.287

In this case, only NudelS2 and NudelS5 were phosphorylated. Therefore, T219, S242, and T245 of Nudel were phosphorylation sites of Cdc2 in vitro. In contrast, Erk2 only phosphorylated T219 and T245. These two sites, with surrounding sequences such as PATP from residues 217 to 220 and PLTP from 243 to 246, respectively, are indeed typical MAPK sites

SIGNOR-274076

P17612

P10636

1

phosphorylation

down-regulates

0.433

However, other kinases, such as cdk5, p38 and pka, also phosphorylate tau at t231tau phosphorylation at t231, s235 and s262 also contributes to the dissociation of tau from microtubules

SIGNOR-171066

Q9UJV3

Q96R06

1

ubiquitination

down-regulates quantity by destabilization

0.309

These data indicated that Mid2 was ubiquitinating Astrin at K409 and targeting Astrin for degradation during cytokinesis.

SIGNOR-278549

Q13131

P49815

1

phosphorylation

up-regulates activity

0.682

However, AMP-activated protein kinase (AMPK), an essential cellular energy sensor, phosphorylates and activates TSC2 [ xref ].

SIGNOR-278981

Q05397

P46937

1

phosphorylation

up-regulates activity

0.284

Then, FAK phosphorylates and activates YAP, leading to the activation and nuclear translocation of YAP/TAZ transcription factor, which is known to be involved in such cellular mechanoresponses [ xref , xref ].

SIGNOR-280099

O75581

P48730

0

phosphorylation

up-regulates activity

0.2

Central to WNT signalosome formation is phosphorylation of LRP6 at multiple sites, with GSK3β phosphorylating LRP6 at S1490 and CK1 family members phosphorylating LRP6 at T1479 and T1493

SIGNOR-275402

Q02750

P00540

0

phosphorylation

up-regulates activity

0.485

Our data indicate that Mos activated MEK1 in vitro as well as in vivo by phosphorylating Ser 222.

SIGNOR-260920

O75150

Q13315

0

phosphorylation

up-regulates

0.443

E3 ubiquitin ligase, a heterodimeric complex of the ringfinger rfn20/rfn40 is phosphorylated by atm.

SIGNOR-175003

Q13315

O43504

1

phosphorylation

up-regulates activity

0.336

Strikingly, we found that the kinase ataxia telangiectasia mutated (ATM) phosphorylated HBXIP at Ser (108).|The knockdown of ATM by siRNA remarkably decreased the levels of serine phosphorylation and blocked the nuclear import of HBXIP.

SIGNOR-279791

P29353

P43403

0

phosphorylation

up-regulates

0.677

The syk-family kinases (syk and zap-70) were able to phosphorylate the y239 and y240 sites, and less efficiently the y317 site on shc1 (iso2).

SIGNOR-59659

O15530

P08069

0

phosphorylation

up-regulates

0.341

Previous studies indicate that optimal activation of PDK1 requires phosphorylation of Tyr373/376 (11, 12, 14, 17), and growth factor receptor activation leads to PDK1 recruitment to the plasma membrane, followed by sequential phosphorylation of Tyr9 and then Tyr373/376

SIGNOR-166710

Q16539

Q9UBK2

1

phosphorylation

up-regulates

0.586

Cytokine stimulation of energy expenditure through p38 map kinase activation of ppargamma coactivator-1we show here that many cytokines activate the transcriptional ppar gamma coactivator-1 (pgc-1) through phosphorylation by p38 kinase, resulting in stabilization and activation of pgc-1 proteinp38 mapk directly phosphorylates pgc-1 on residues threonine 262, serine 265, and threonine 298

SIGNOR-112774

P78352

Q9NZJ5

0

phosphorylation

up-regulates activity

0.268

To elucidate the molecular mechanism, we found that activated PERK phosphorylates CAMP response element binding protein (CREB) and PSD95 directly at the S129 and T19 residues, respectively.

SIGNOR-280004

P16885

P06241

0

phosphorylation

up-regulates activity

0.575

The phosphorylation of purified phospholipase C-gamma 1 (PLC-gamma 1) and PLC-gamma 2 by src-family-protein tyrosine kinases (PTKs) P56lck, p53/56lyn, p59hck, p59fyn, and p60src was studied in vitro. All five PTKs phosphorylated PLC-gamma 1 and PLC-gamma 2, suggesting that both PLC-gamma isozymes can be phosphorylated in cells by any of the src-family PTKs in response to the activation of cell surface receptors.

SIGNOR-249340

Q9Y281

Q15569

0

phosphorylation

down-regulates activity

0.321

Like TESK1, TESK2 phosphorylated cofilin specifically at Ser-3 and induced formation of actin stress fibers and focal adhesionsExpression of cofilin or S3A-cofilin into HeLa cells induced marked decreases in rhodamine-phalloidin staining due to the actin binding and -depolymerizing activity of cofilin

SIGNOR-246719

P23769

P01222

1

transcriptional regulation

up-regulates quantity by expression

0.39

Pit-1, is necessary but not sufficient to allow basal transcription of the mTSHβ gene.The analysis of the mTSHβ gene described in this report provides evidence for the participation of a zinc finger factor, GATA-2, with a POU homeodomain partner, Pit-1, on a such a composite element.In summary, we have shown the requirement for at least two different classes of transcription factors to regulate mTSHβ gene expression. Both GATA-2 and Pit-1 can bind independently to the P1 region of the promoter, form a heteromeric complex with DNA, and functionally synergize to activate TSHβ promoter activity.

SIGNOR-267253

P11309

Q99683

1

phosphorylation

down-regulates

0.28

Pim1 phosphorylates and negatively regulates ask1-mediated apoptosispim1 phosphorylation of ask1 on ser83 inhibited ask1-mediated c-jun n-terminal kinase phosphorylation

SIGNOR-187905

Q13315

Q14738

1

phosphorylation

up-regulates activity

0.297

In the present study, we demonstrate that ataxia-telangiectasia mutated (ATM) directly phosphorylates and specifically regulates B56γ3, B56γ2 and B56δ, after DNA damage. We further show that phosphorylation of B56γ3 at Ser510 leads to an increase in B56γ3-PP2A complexes, and direction of PP2A phosphatase activity toward the substrate p53, activating its tumor-suppressive functions. we show that Ser510 phosphorylation significantly enhances the ability of B56γ3 to inhibit cell proliferation and anchorage-independent growth.

SIGNOR-276319

O95382

Q16539

1

phosphorylation

up-regulates activity

0.2

These data indicate that MKK6 phosphorylates p38 MAP kinase on Thr-180 and Tyr-182, the sites of phosphorylation that activate p38 MAP kinase

SIGNOR-260916

P03186

Q9Y6K9

1

deubiquitination

down-regulates activity

0.2

In the current study, we have found that BPLF1 interferes with innate immune activation by targeting multiple intermediates along the TLR signal transduction pathway, including TRAF6, NEMO, and IκBα. BPLF1 can remove ubiquitin tags from proteins in the TLR signaling cascade. This inhibits TLR signaling and decreases the expression of immune response genes.

SIGNOR-266743

P08047

P24821

1

transcriptional regulation

up-regulates quantity by expression

0.2

Sp1 and Ets1 are potent transactivators of the TN-C promoter.

SIGNOR-261600

Q16581

P25098

0

phosphorylation

down-regulates activity

0.2

These findings indicated that agonist-induced C3aR phosphorylation by GRK2 promotes C3aR desensitization.

SIGNOR-279044

Q15811

Q96CN9

0

relocalization

up-regulates activity

0.2

GFP-GCC88 was immunoprecipitated by both the short and long form of ITSN-1 but not with FLAG-Rheb (Figure 4A). These data demonstrate that both GCC88 and ITSN-1 are part of a complex. 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-260600

Q96T23

P53350

0

phosphorylation

up-regulates activity

0.352

Moreover, CDK1 phosphorylates RSF1 at Ser1375, and this phosphorylation is necessary for PLK1 recruitment. Subsequently, PLK1 phosphorylates RSF1 at Ser1359, stabilizing PLK1 deposition.

SIGNOR-273590

P16284

P06239

0

phosphorylation

up-regulates activity

0.588

We demonstrated that phosphorylation of PECAM-1 by Src or Csk family kinases was sufficient to trigger its association with SHP-2. Moreover, it was able to promote binding of PECAM-1 to SHP-1, a SHP-2-related protein-tyrosine phosphatase expressed in hemopoietic cells. Taken together, these findings indicated that the Src and Csk families of kinases are strong candidates for mediating tyrosine phosphorylation of PECAM-1 and triggering its association with SH2 domain-containing phosphatases under physiological circumstances.

SIGNOR-262742

Q15831

Q14680

1

phosphorylation

up-regulates

0.2

Site-directed mutagenesis indicated that thr167 and ser171, located between the dfg and ape motifs in the activation loop or t-loop, need to be autophosphorylated for melk to be active as a protein kinase (fig. 5). These sites are conserved in all other ampk-related protein kinases (fig. 4a), and the site corresponding to thr167 has been shown to be phosphorylated by protein kinase lkb1 (5).

SIGNOR-141038

P51955

Q5FBB7

1

phosphorylation

up-regulates

0.2

Here we show that nek2a phosphorylates human sgo1 and such phosphorylation is essential for faithful chromosome congression in mitosis. phosphorylation sites were mapped to ser(14) and ser(507)

SIGNOR-156882

P53350

O94901

1

phosphorylation

down-regulates activity

0.453

Here, we show that SUN1, located in the INM, undergoes mitosis-specific phosphorylation on at least 3 sites within its nucleoplasmic N-terminus. We further identify Cdk1 as the kinase responsible for serine 48 and 333 phosphorylation, while serine 138 is phosphorylated by Plk1. Together, these data support a model whereby mitotic phosphorylation of SUN1 disrupts interactions with nucleoplasmic binding partners, promoting disassembly of the nuclear lamina and, potentially, its chromatin interactions.

SIGNOR-263098

Q9Y478

Q13586

1

phosphorylation

down-regulates activity

0.2

STIM1 is a novel exercise‐regulated AMPK substrate. Phosphorylation of STIM1 by AMPK suppresses SOCE

SIGNOR-277298

Q9UHI6

P41162

0

transcriptional regulation

down-regulates quantity by repression

0.739

ETV3 target genes including etv3, ddx20, and dusp6 provide negative feedback regulation of ETV3 production and activity. Negative feedback along with constitutive instability may serve to tightly regulate ETV3 abundance. Our date suggest that phosphorylation by ERK2 relieves repression by ETV3, allowing activation of cell cycle control genes including myc, components of the NF-κB pathway, and genes required form RNA processing and translation.

SIGNOR-262779

O75592

P10275

1

ubiquitination

down-regulates quantity by destabilization

0.2

We identified several E3 ligases as strong candidates responsible for AR and MYC protein loss as HECTD4, MYCBP2, and TRIM49. HECTD4 and MYCBP2 target AR and MYC for degradation while TRIM49 appears to promote AR and MYC stability. We have shown that these E3 ligases in turn are directly regulated by MYC. MYC in turn represses the expression of ubiquitin ligases, HECTD4 and MYCBP2 that promote AR and MYC protein degradation, further suppressing MYC and AR in a feed forward loop.

SIGNOR-267149

P04150

Q13886

1

transcriptional regulation

up-regulates quantity by expression

0.321

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

SIGNOR-256119

O15550

P68431

1

demethylation

down-regulates activity

0.2

Ubiquitously Transcribed Tetratricopeptide Repeat on chromosome X (UTX) and Jumonji D3 (JMJD3) as novel histone demethylases that catalyze the removal of di- and trimethyl groups on histone H3 lysine 27, thereby promoting target gene activation.

SIGNOR-260017

O60814

Q14493

0

translation regulation

up-regulates quantity by expression

0.2

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

SIGNOR-265383

Q9UPN9

P35222

1

ubiquitination

down-regulates quantity by destabilization

0.457

TRIM33 ubiquitylates nuclear beta-catenin.|Tumour suppressor TRIM33 targets nuclear beta-catenin degradation.

SIGNOR-278578

Q96PE2

P33981

0

phosphorylation

down-regulates activity

0.2

Because Mps1 also phosphorylates ARHGEF17, the Mps1\u2013ARHGEF17 complex is short lived and promotes its own dissociation, which in turn releases Mps1 and ARHGEF17 from the kinetochore.|ARHGEF17 and Mps1 interact during mitosis and Mps1 phosphorylates ARHGEF17.

SIGNOR-279352