GleghornLab/Signor_2class · Datasets at Hugging Face

IdA string	IdB string	labels int64	mechanism string	effect string	score float64	sentence string	signor_id string
P27361	Q05469	1	phosphorylation	up-regulates activity	0.415	Thus, activation of the ERK pathway appears to be able to regulate adipocyte lipolysis by phosphorylating HSL on Ser(600) and increasing the activity of HSL.	SIGNOR-249470
P50750	P50613	0	phosphorylation	up-regulates activity	0.551	Cdk7 activates Cdk9 in vitro .\|Cdk7 phosphorylates wild-type Cdk9 on Thr186, resulting in increased activity towards a recombinant GST-Spt5 substrate.	SIGNOR-279455
P18846	P51812	0	phosphorylation	up-regulates activity	0.318	ATF1 and CREB can be phosphorylated by Rsk2 which is a protein kinase directly activated by Erk MAP kinase. These results suggest a signaling pathway in which Erk MAP kinase activates the c-fos enhancer by direct phosphorylation of p62TCF and by activation of Rsk related kinases that phosphorylate ATF1 and CREB.\|ATF1 and CREB can be phosphorylated by Rsk2 which is a protein kinase directly activated by Erk MAP kinases.	SIGNOR-280117
Q8N752	P10071	1	phosphorylation	up-regulates	0.333	Ci is phosphorylated by pka at multiple sites priming phosphorylation by both gsk3 and cki, leading to partial proteolysis. The pka, gsk3, and cki sites are conserved in gli2 and gli3, vertebrate homologs of ci that are similarly processed	SIGNOR-144554
P16220	Q6SA08	0	phosphorylation	up-regulates	0.578	Tssk5, a novel member of the testis-specific serine/threonine kinase family, phosphorylates creb at ser-133, and stimulates the cre/creb responsive pathway.	SIGNOR-138289
P07947	Q969T9	1	phosphorylation	up-regulates activity	0.304	Using dominant-negative, constitutively active mutants, RNAi, and pharmacological studies, we demonstrated that phosphorylation of WBP2 at Tyr192 and Tyr231 could be regulated by c-Src and c-Yes kinases.We further showed that abrogating WBP2 phosphorylation impaired >60% of ERα reporter activity, putatively by blocking nuclear entry of WBP2 and its interaction with ERα.	SIGNOR-273582
P19544	O60500	1	transcriptional regulation	up-regulates quantity by expression	0.487	The Wilms tumor suppressor gene (WT1) is a zinc-finger-containing transcription factor that is coexpressed with NPHS1 in differentiated podocytes; gel shift binding assays demonstrate that a recombinant WT1 protein can bind and activate the 186-bp NPHS1 fragment in a sequence-specific manner	SIGNOR-252299
P45983	Q13526	1	phosphorylation	up-regulates quantity by stabilization	0.272	Mechanistically, the JNK kinases directly bind to and phosphorylate PIN1 at Ser115, and this phosphorylation prevents PIN1 mono-ubiquitination at Lys117 and its proteasomal degradation.	SIGNOR-277562
P63000	Q9H0H5	0	gtpase-activating protein	down-regulates activity	0.586	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-260512
Q05397	Q13164	0	phosphorylation	up-regulates activity	0.291	Remarkably, the reduction in ERK5 expression correlated with decreased p-FAK(Tyr397) staining, consistent with the requirement of ERK5 for mediating FAK activation in vivo (Fig. 6C).\|We confirmed that JWG-045, a novel pharmacological inhibitor of ERK5 exhibiting significantly reduced affinity for BRD4 compared with XMD8-92 (25, 26), did not suppress FAK phosphorylation at Tyr397 in MDA-MB-231 cells (Supplementary Fig. S3B and C).	SIGNOR-279304
Q13480	P12931	0	phosphorylation	up-regulates	0.704	Using both mutagenesis and mass spectrometry approaches, y242, y259, y317, y373 and y627 of gab1 were identified to be phosphorylated by c-src a gab1 mutant with substitutions of the src phosphorylation sites failed to promote hgf-induced dna synthesis	SIGNOR-236314
P27361	Q92934	1	phosphorylation	down-regulates	0.483	Erk-1 map kinase prevents tnf-induced apoptosis through bad phosphorylation and inhibition of bax translocation in hela cells.	SIGNOR-188172
P68400	Q00613	1	phosphorylation	up-regulates activity	0.37	Transcriptional activity and DNA binding of heat shock factor-1 involve phosphorylation on threonine 142 by CK2.	SIGNOR-250898
O14974	P04049	0	phosphorylation	down-regulates activity	0.274	In hESC, Raf-1 directly phosphorylates and inactivates MYPT1, and this process requires kinase active Raf-1 protein.	SIGNOR-278979
P23396	P06493	0	phosphorylation	up-regulates	0.362	These results suggest that the phosphorylation of rps3 by cdk1 occurs at thr221 during g2/m phase and, moreover, that this event is important for nuclear accumulation of rps3.	SIGNOR-176131
P36956	O75874	1	transcriptional regulation	up-regulates quantity by expression	0.282	IDH1 gene transcription is sterol regulated and activated by SREBP-1a and SREBP-2 in human hepatoma HepG2 cells\|evidence that IDH1 may regulate lipogenesis in hepatic cells	SIGNOR-253132
O95096	Q8TAM6	1	transcriptional regulation	up-regulates quantity by expression	0.249	Further study revealed that Nkx2.2 could bind JN promoter and its overexpression increase the promoter activity of JN.	SIGNOR-268965
P06493	P06400	1	phosphorylation	down-regulates	0.688	The retinoblastoma gene product (prb) is a nuclear phosphoprotein that is thought to play a key role in the negative regulation of cellular proliferation. The active form of prb is underphosphorylated. Using synthetic peptides corresponding to potential cdc2 phosphorylation sites, we have developed a strategy which has allowed the identification of five sites. S249, t252, t373, s807 and s811 are phosphorylated in vivo, and in each case these sites correspond closely to the consensus sequence for phosphorylation by p34cdc2.	SIGNOR-21564
O14757	P19838	1	phosphorylation	down-regulates	0.275	Taken together, the above findings suggest that chk1 phosphorylates p50 at s329 and further, that this phosphorylation blocks p50 dna binding.	SIGNOR-195208
P17252	Q96QS3	1	phosphorylation	up-regulates activity	0.2	We confirm that ARX is phosphorylated by PRKCA and demonstrate phosphorylation at serine 174. We demonstrate that phosphorylation is required for correct transcriptional activity of the ARX protein using transcriptome-wide analysis of gene expression of phospho-null mutants (alanines replacing serines) compared to ARX wild-type (ARX-WT) overexpressed in pancreatic alpha TC cells.	SIGNOR-277418
O43426	Q9P286	0	phosphorylation	up-regulates activity	0.2	We identified two novel Pak5 substrates, Pacsin1 and Synaptojanin1, proteins that directly interact with one another to regulate synaptic vesicle endocytosis and recycling. Pacsin1 and Synaptojanin1 were phosphorylated by Pak5 and the other group II Paks in vitro, and Pak5 phosphorylation promoted Pacsin1-Synaptojanin1 binding both in vitro and in vivo.	SIGNOR-263026
P27361	Q93045	1	phosphorylation	down-regulates activity	0.352	SCG10, a growth cone-enriched MT-destabilizing protein, has been recently characterized as an in vitro substrate for various serine/threonine kinases including PKA, MAP kinase, and CDK (19). We have found that SCG10 is phosphorylated in vivo in developing rat brain.\| The sites for MAP kinase phosphorylation were identified as Ser-62 and Ser-73 of SCG10\|By expressing a series of phosphorylation site mutants, we showed that the MT-destabilizing effect of SCG10 could be modulated. While the nonphosphorylatable mutant showed higher activity than the wild-type protein, the activity of the mutant in which phosphorylation on all four sites was mimicked by an aspartate residue was greatly reduced. These data suggest that the nonphosphorylated state of SCG10 represents the most active form of the protein.	SIGNOR-249115
Q13489	Q86VP3	1	polyubiquitination	down-regulates quantity by destabilization	0.286	Under basal conditions, PACS-2 underwent K48-linked poly-ubiquitination, resulting in PACS-2 proteasomal degradation. Biochemical assays showed cIAP-1 and cIAP-2 interacted with PACS-2 in vitro and co-immunoprecipitation studies demonstrated that the two cIAPs bound PACS-2 in vivo. More importantly, both cIAP-1 and cIAP-2 directly mediated PACS-2 ubiquitination in a cell-free assay.	SIGNOR-272852
P04629	Q13191	0	ubiquitination	down-regulates quantity	0.276	Cbl-b modulated TrkA ubiquitination and function in the dorsal root ganglion of mice.\|Viral expression of constitutively active Cbl-b in DRGs of osteoarthritic mice effectively repressed TrkA protein level and more importantly, alleviated mechanical allodynia and heat hyperalgesia.	SIGNOR-278690
P08246	P25116	1	cleavage	up-regulates activity	0.43	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.\|Protease-activated receptors (PARs) mediate cell activation after proteolytic cleavage of their extracellular amino terminus.\|Protease-activated receptors (PARs) mediate cell activation after proteolytic cleavage of their extracellular amino terminus	SIGNOR-263565
P25963	Q9UHD2	0	phosphorylation	down-regulates quantity by destabilization	0.456	Nuclear factor-kappaB activation depends on phosphorylation and degradation of its inhibitor protein, IkapapB. TBK-1 and IKK-i phosphorylate Ser36 of IkappaBalpha.	SIGNOR-246643
O60500	P12931	0	phosphorylation	up-regulates activity	0.48	Inhibition of Src kinase dependent Nephrin phosphorylation achieved by incubation of WT-Nephrin-overexpressing cells with 1 mum PP2 abolished the positive effect of Nephrin on GSIR (XREF_FIG D).\|We were able to demonstrate a complete prevention of Nephrin phosphorylation, confirming that Nephrin phosphorylation is mediated by Src.	SIGNOR-280129
P42768	P06241	0	phosphorylation	up-regulates activity	0.561	As shown in XREF_FIG F, Fyn immunoprecipitates from activated T cells induced the tyrosine phosphorylation of WASp, but neither WASpDeltaPro nor WASpY291F mutant proteins were phosphorylated in this assay.	SIGNOR-279333
P48729	O75581	1	phosphorylation	up-regulates	0.552	We show that wnt induces sequential phosphorylation of lrp6 by gsk3 and casein kinase 1, and this dual phosphorylation promotes the engagement of lrp6 with the scaffolding protein axin.Site ii, like site i, was phosphorylated, as detected by means of a phospho-specific antibody (ab1493, for phosphorylated t1493 in lrp6)	SIGNOR-143034
P54756	Q14938	0	transcriptional regulation	up-regulates quantity	0.2	For example, within the NFI targetome, we identified 6 collagen genes, 13 genes encoding potassium channel or glutamate receptor subunits and a range of factors related to axon guidance (e.g. Slit1, Robo1, Epha4, Epha5, Epha8)	SIGNOR-268909
P06213	P23467	0	dephosphorylation	down-regulates	0.344	Identification of tyrosine phosphatases that dephosphorylate the insulin receptor.	SIGNOR-75997
Q9HCE7	Q13873	1	ubiquitination	down-regulates	0.56	Smurf1 and smurf2 are e3 ubiquitin ligases known to suppress tgf-beta signaling through degradation of smads and receptors for tgf-beta and bmps.	SIGNOR-153402
P12931	Q13177	1	phosphorylation	up-regulates	0.562	Pak2 became tyrosine phosphorylated in its n-terminal regulatory domain, where y130 was identified as the major phosphoacceptor site. Tyrosine phosphorylation-mediated superactivation of pak2 could be induced by overexpression of different src kinases or by inhibiting cellular tyrosine phosphatases with pervanadate and could be blocked by the src kinase inhibitor pp1 or by mutating the y130 residue.	SIGNOR-92460
Q96LC9	P28482	0	phosphorylation	up-regulates	0.253	Phosphomimetic mutation of this site (s74d) moderately enhanced bmf apoptotic activity in vivo.22 here, we demonstrate a previously unrecognized mode of regulation of bmf. We show that b-raf-mek-erk2 signaling regulates bmf phosphorylation at serine 74 and serine 77. Phosphorylation of serine 77 downregulates the pro-apoptotic activity of bmf.	SIGNOR-195475
O60674	Q99683	1	phosphorylation	down-regulates quantity by destabilization	0.367	Furthermore, JAK2, but not JAK1, directly bound to and phosphorylated ASK1 at Tyr-718, leading to an enhanced association of ASK1 with SOCS1 and subsequent ASK1 degradation.	SIGNOR-276145
Q9BZL6	Q02156	0	phosphorylation	up-regulates	0.2	In cells transfected with pkc? Or pkc? The phosphorylation of ser876 was markedly more pronounced than the phosphorylation of ser706/ser710 / the phosphorylation of ser706/ser710 in pkd2 reflects the activation of the kinase.	SIGNOR-89415
O96013	P35222	1	phosphorylation	up-regulates	0.286	Pak4 interacts with and phosphorylates _-catenin on ser675, which promotes the tcf/lef transcriptional activity and stabilizes _-catenin through inhibition of its degradation.	SIGNOR-191557
P06400	P05771	0	phosphorylation	down-regulates activity	0.352	The exact mechanism by which PKCbeta degrades RB is unknown.\|To attribute increased RB phosphorylation specifically to PKC\u03b2, we transiently transfected PKC\u03b2 -/- hepatocytes, and reintroduction of PKC\u03b2 specifically resulted in increased in phospho-RB (Ser780) levels, further supporting that PKC\u03b2 phosphorylates RB specifically at Ser780 without affecting phosphorylation at other residues (Ser807 and Ser811) (Figure xref ).	SIGNOR-280083
P53041	Q9UPZ9	1	dephosphorylation	down-regulates activity	0.2	MAK and MRK require dual phosphorylation in a TDY motif catalyzed by an unidentified human threonine kinase and tyrosine autophosphorylation.\| Protein phosphatase 5 (PP5) interacts with MRK in a complex and dephosphorylates MRK at T157 in vitro and in situ.	SIGNOR-248541
P12931	Q9UQB3	1	phosphorylation	up-regulates activity	0.329	Furthermore, according to our data from immunoprecipitation to py20 antibody, c-Src can phosphorylate delta-catenin on Y1073, Y1176, Y1179 and Y1112, with the predominant sites being Y1073, Y1112 and Y1176.\|Interestingly, we found that c-Src can increase the stability of delta-catenin in MEF cells.	SIGNOR-278327
Q06124	P42224	1	dephosphorylation	down-regulates activity	0.743	SHP-2 is a dual-specificity phosphatase involved in Stat1 dephosphorylation at both tyrosine and serine residues in nuclei\|In SHP-2-/- mouse fibroblast cells, Stat1 phosphorylation at both the tyrosine residue Tyr(701) and the serine residue Ser(727) \|Overexpression of SHP-2 in 293T cells inhibited IFNgamma-dependent Stat1 phosphorylation and suppressed Stat1-dependent induction of luciferase activity.	SIGNOR-248673
Q9UPW6	Q9C0K0	1	transcriptional regulation	down-regulates quantity	0.495	Satb2 represses the transcription of Nr4a2. The misexpression of Nr4a2 together with Ctip2 induces expression of SubC-specific genes in wild-type Rsp, and simultaneous knockdown of these two genes in Rsp Satb2-mutant cells prevents their fate transition to SubC identity. Thus, Satb2 serves as a determinant gene in the Rsp regionalization by repressing Nr4a2 and Ctip2 during cortical development	SIGNOR-268931
Q9BYB0	Q15398	0	relocalization	up-regulates activity	0.2	SHANK proteins are ‘master’ scaffolding proteins that tether and organize intermediate scaffolding proteins. They are located at excitatory synapses, where they are crucial for proper synaptic development and function. SAPAP proteins subsequently bind to the PDZ domain of members of the SHANK protein family. SHANK proteins then bind to the actin cytoskeleton and to Homer protein, which in turn interacts with mGluRs. Through these extended links, PSD95, SAPAP, SHANK and Homer proteins form a quaternary complex that brings together mGluR and NMDAR complexes in the PSD (FIG. 3).	SIGNOR-264600
O95747	Q9H4A3	0	phosphorylation	up-regulates	0.484	Activation of wnk1 coincides with the phosphorylation and activation of two wnk1 substrates, namely, the protein kinases ste20/sps1-related proline alanine-rich kinase (spak) and oxidative stress response kinase-1 (osr1)	SIGNOR-151659
Q9NWF9	O00206	1	ubiquitination	down-regulates quantity by destabilization	0.388	Here we describe how a RING finger protein, Triad3A, acts as an E3 ubiquitin-protein ligase and enhances ubiquitination and proteolytic degradation of some TLRs. Triad3A overexpression promoted substantial degradation of TLR4 and TLR9 with a concomitant decrease in signaling, but did not affect TLR2 expression or signaling.	SIGNOR-271504
Q12834	Q9UHD2	0	phosphorylation	down-regulates activity	0.2	It was found that TBK1 phosphorylates both Cdc20 as well as Cdh1 (Figure 2F).	SIGNOR-279766
Q9ULV5	P52564	0	phosphorylation	up-regulates activity	0.2	Regulation of Hsf4b nuclear translocation and transcription activity by phosphorylation at threonine 472\| At the upstream, MEK6 was found to interact with Hsf4b and enhance Hsf4b's nuclear translocation and transcription activity, probably by phosphorylation at sites such as T472. Taken together, our results suggest that phosphotylation of Hsf4b at T472 by protein kinases such as MEI	SIGNOR-275493
P01019	P08311	0	cleavage	up-regulates activity	0.643	Cathepsin G, elastase, and proteinase 3 are serine proteinases released by activated neutrophils. Cathepsin G can cleave angiotensinogen to release angiotensin II, but this activity has not been previously reported for elastase or proteinase 3. In this study we show that elastase and proteinase 3 can release angiotensin I from angiotensinogen and release angiotensin II from angiotensin I and angiotensinogen.	SIGNOR-256312
P06493	Q8NEB9	1	phosphorylation	down-regulates	0.42	We show that vps34 is phosphorylated on thr159 by cdk1, thr159 phosphorylation negatively regulates the ptdins3 kinase activity of vps34 and autophagy	SIGNOR-165768
Q06187	P05771	0	phosphorylation	down-regulates activity	0.382	We provide direct evidence that PKCbeta acts as a feedback loop inhibitor of Btk activation. Inhibition of PKCbeta results in a dramatic increase in B-cell receptor (BCR)-mediated Ca2+ signaling. We identified a highly conserved PKCbeta serine phosphorylation site in a short linker within the Tec homology domain of Btk. Mutation of this phosphorylation site led to enhanced tyrosine phosphorylation and membrane association of Btk, and augmented BCR and FcepsilonRI-mediated signaling in B and mast cells, respectively. \| This deductive analysis indicated that PKCbeta phosphorylates S180 in the region bisecting the Btk motif (BM) and the PRR of the TH domain.	SIGNOR-249110
P08575	P06241	1	dephosphorylation	up-regulates activity	0.73	On the membrane SKAP55, via its phosphorylated Tyr-271, further binds the SH2 domain of Fyn to replace the low-affinity bound inhibitory site of the kinase. Consequently, CD45 may have transiently disassociated with the Tyr-232 residue of SKAP55 through dephosphorylation and simultaneously interacted with the released the phosphorylated inhibitory tyrosine residue of Fyn for dephosphorylation, resulting in activation of the Src family kinase Fyn and initiation of TCR-engaged signal transduction.	SIGNOR-248352
P42574	Q4V328	1	cleavage	up-regulates activity	0.414	These results suggest that the region of GRASP‐1 downstream of the Caspase‐3‐cleavage site is capable of activating the JNK signaling pathway by enhancing the phosphorylation of JNK. these results suggest that full length GRASP‐1 does not enhance JNK pathway activity, possibly due to the inhibitory effect of the N‐terminal fragment on the C‐terminal fragment. In contrast, Caspase‐3 cleavage of GRASP‐1 releases the C‐terminal fragment, which in turn activates JNK signaling by serving as a scaffold protein.	SIGNOR-260641
P41161	O00712	0	transcriptional regulation	down-regulates quantity	0.2	By integrating transcriptomic profiling (RNA-seq) of Nfia- and Nfix-deficient GNPs with epigenomic profiling (ChIP-seq against NFIA, NFIB and NFIX, and DNase I hypersensitivity assays), we reveal that these transcription factors share a large set of potential transcriptional targets, suggestive of complementary roles for these NFI family members in promoting neural development	SIGNOR-268880
O60260	O95140	1	ubiquitination	down-regulates quantity	0.2	Parkin and PINK1 are required for ubiquitination of MFN-1 and MFN-2. Decreases in MFN-1 and MFN-2 protein levels seen at later timepoints are difficult to interpret as it is unclear whether this is due to degradation by the proteasome and/or loss of whole mitochondria by mitophagy.	SIGNOR-272780
P16070	P17612	0	phosphorylation	up-regulates	0.2	Pka can phosphorylate ser316 directly cd44 s291a and s316a mutants may disrupt downstream signalling events by displacing endogenous cd44 from plasma membrane microdomains.	SIGNOR-147208
Q96EP1	Q96GM5	1	polyubiquitination	down-regulates quantity by destabilization	0.307	Here we report that CHFR interacts with BRG1, SNF5, and BAF60a of the SWI/SNF-like BAF complex and ubiquitinates them to target for degradation through a proteasome-mediated pathway, and that SRG3/mBAF155 stabilizes these components by blocking their interaction with CHFR. These results suggest that CHFR enhances the degradation of the components of the SWI/SNF-like BAF complex by inducing their poly-ubiquitination.	SIGNOR-271459
P12931	P17655	1	phosphorylation	up-regulates activity	0.525	CAPN2 itself was a bone fide substrate of SRC that was primarily phosphorylated at Y625 by SRC and exhibited increased proteolysis activity upon phosphorylation.	SIGNOR-277598
P68400	P30305	1	phosphorylation	up-regulates activity	0.338	Mass spectrometry analysis demonstrates that at least two serine residues, Ser-186 and Ser-187, are phosphorylated in vivo. \| Finally, we demonstrate that phosphorylation of CDC25B by protein kinase CK2 increases the catalytic activity of the phosphatase in vitro as well as in vivo.	SIGNOR-250836
Q99986	Q05655	0	phosphorylation	down-regulates activity	0.285	PKC\u03b4 phosphorylates VRK1 on Ser-355 in vitro.\|PKCdelta negatively regulates VRK1 kinase activity in vitro.	SIGNOR-278219
P17612	P15924	1	phosphorylation	down-regulates activity	0.328	HeLa cells treated with forskolin indicated that stimulation of protein kinase A in transfected cells could decrease the interaction of DP.AN.SerC23 with keratin IF networks. phosphorylation of Ser-C23 could destabilize interactions that occur either directly through this 20 residue sequence or that are dependent on its correct conformation	SIGNOR-250353
P49841	Q9BZS1	1	phosphorylation	down-regulates quantity by destabilization	0.285	Our previous study showed, by mass spectrometry analysis, that GSK-3β phosphorylates Foxp3 at Ser270 and Ser275	SIGNOR-277245
Q9Y252	P53667	1	polyubiquitination	down-regulates quantity by destabilization	0.432	Consistent with a role in axonal growth, we found that Rnf6 binds to, polyubiquitinates, and targets LIMK1 for proteasomal degradation in growth cones of primary hippocampal neurons.	SIGNOR-271481
Q5SGD2	O75460	1	dephosphorylation	up-regulates activity	0.309	Overall, our study establishes that PP2Ce mediated IRE1 regulation in ER stress signaling is a potentially important molecular basis for its genetic contribution to metabolic syndrome.Lin et al. [36] have reported that different durations and composition of ER stress signaling pathways can dictate cell fate and the balance between survival and death.\|Recombinant wildtype PP2Ce, but not a phosphatase-dead mutant (PP2Ce-D302A), effectively dephosphorylated the phosphor-Ser724 site of IRE1\u03b1 protein (p-IRE1\u03b1) (A).	SIGNOR-277074
P36507	P27361	1	phosphorylation	up-regulates	0.742	The primary structure of mek, a protein kinase that phosphorylates the erk gene product	SIGNOR-19244
Q8NEZ5	P04637	1	ubiquitination	down-regulates quantity by destabilization	0.338	We demonstrate here that SCFFbxo22-KDM4A is a senescence-associated E3 ligase targeting methylated p53 for degradation. We find that Fbxo22 is highly expressed in senescent cells in a p53-dependent manner, and that SCFFbxo22 ubiquitylated p53 and formed a complex with a lysine demethylase, KDM4A. \|SCFFbxo22 forms a ternary complex with p53 and KDM4A that targets methylated p53 for degradation.	SIGNOR-273448
P36894	O15198	1	phosphorylation	up-regulates activity	0.706	To ascertain whether overexpression of BMPr1A can initiate adipocyte lineage commitment in the absence of its BMP ligand, constitutively active (CA)-BMPr1A and CA-BMPr1B were expressed in C3H10T1/2 stem cells using a mouse stem cell virus (MSCV) retroviral system. […]Thus, their overexpression provoked a substantial rise in the phosphorylation of Smad1/5/8 and p38 MAPK, known downstream phosphorylated intermediates in the BMP signaling pathway.	SIGNOR-255772
P35813	P50750	1	dephosphorylation	down-regulates activity	0.493	Taken together, our data indicate that PPM1A and to some extent PPM1B are important negative regulators of P-TEFb function	SIGNOR-248490
P17252	P15172	1	phosphorylation	down-regulates activity	0.363	FGF inactivates myogenic helix-loop-helix proteins through phosphorylation of a conserved protein kinase C site in their DNA-binding domains.	SIGNOR-248845
O00141	P21796	1	phosphorylation	down-regulates quantity	0.2	As hypothesized based upon our observation that activated SGK-1 reduces VDAC-1 protein levels, sgk-1 overexpression normalizes the shortened lifespan of vdac-1 transgenics .\|Taken together, these data indicate that Ser104 phosphorylation of VDAC1 by SGK1 increases its ubiquitination and subsequent cellular clearance.	SIGNOR-278988
Q16566	Q8N5S9	0	phosphorylation	up-regulates	0.62	Phosphorylation of ca(2+)/cam-bound camkiv on its activation loop threonine (residue thr(200) in human camkiv) by ca(2+)/calmodulin-dependent kinase kinase leads to increased camkiv kinase activity.	SIGNOR-134649
Q9BXL7	P62714	0	dephosphorylation	down-regulates activity	0.2	NF-kappaB activation is triggered by PKCtheta-dependent phosphorylation of Carma1 after TCR/CD28 co-stimulation. PKCtheta-phosphorylated Carma1 was suggested to function as a molecular scaffold that recruits preassembled Bcl10-Malt1 complexes to the membrane\|we demonstrate that PP2A removes PKCtheta-dependent phosphorylation of Ser645 in Carma1, and show that maintenance of this phosphorylation is correlated with increased T-cell activation.	SIGNOR-248607
P30411	P43250	0	phosphorylation	down-regulates activity	0.288	Ligand-induced phosphorylation is found at Ser339 and Ser346/Ser348 that could be executed by several G protein-coupled receptor kinases. 32P labeling of peptide 3 containing pS346/pS348 was enhanced 1.5–3-fold as compared with mock-transfected cells in the order GRK6 < GRK5 < GRK2 < GRK4α < GRK3. several endogenous GRKs may phosphorylate the B2R and that the various GRKs, even without apparent effect on total GPCR phosphorylation levels, may induce distinct phosphorylation patterns with possible functional consequences for receptor desensitization and sequestration.	SIGNOR-251207
P49840	Q96RR4	1	phosphorylation	down-regulates	0.269	Cdk5 and gsk3 phosphorylate ser-129, ser-133, and ser-137. Mutation of ser-129, ser-133, and ser-137 increases autonomous activity with little change in ca2 /cam-dependent activity.	SIGNOR-198122
P17612	Q9NR82	1	phosphorylation	up-regulates activity	0.2	We conclude that phosphorylation of S53 on the amino terminus of Kv7.5 is essential for PKA-dependent enhancement of channel activity in response to βAR activation in vascular and airway smooth muscle cells.	SIGNOR-265980
O60729	Q9NQR1	1	dephosphorylation	down-regulates quantity by destabilization	0.2	The dephosphorylation of S29 during late mitosis by the Cdc14 phosphatases was required for APC(cdh1)-mediated ubiquitination of PR-Set7 and subsequent proteolysis.	SIGNOR-248339
Q9Y5S8	P05771	0	phosphorylation	up-regulates activity	0.2	Site-directed mutagenesis and isothermal titration calorimetry indicated that protein kinase C-beta1 phosphorylates Nox1 at threonine 429. Moreover, Nox1 threonine 429 phosphorylation facilitated the association of Nox1 with the NoxA1 activation domain and was necessary for NADPH oxidase complex assembly	SIGNOR-264729
P42229	Q9P1W9	1	transcriptional regulation	up-regulates quantity by expression	0.41	The results of 2 microarray experiments demonstrated that the aberrant activation of STAT proteins by Flt3-ITDs resulted in the up-regulation of several STAT5-responsive genes, such as Pim-1, Pim-2, and members of the SOCS (suppressor of cytokine signaling) protein family. These results are particularly interesting because recent data point to an important role of Pim kinases in the antiapoptosis of hematopoietic cells.	SIGNOR-249622
P25963	Q15418	0	phosphorylation	up-regulates activity	0.386	Mitogen activated ribosomal S6 kinase (p90 rsk1) phosphorylates IkappaBalpha at S32, binds IkappaBalpha in vivo, and overexpression of dominant negative p90 rsk1 inhibits degradation of IkappaBalpha in response to TPA.	SIGNOR-279311
Q9UHD2	Q04759	0	phosphorylation	up-regulates activity	0.2	TBKBP1 recruits TBK1 to protein kinase C-theta (PKCθ) through a scaffold protein, CARD10. This enables PKCθ to phosphorylate TBK1 at Ser 716, a crucial step for TBK1 activation	SIGNOR-272472
P08069	O15530	1	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
P48729	O14503	1	phosphorylation	down-regulates quantity by destabilization	0.2	CK1α-mediated phosphorylation of DEC1 on a conserved degron is required for DEC1 degradation.	SIGNOR-276851
Q8IWA4	O60260	0	ubiquitination	down-regulates quantity	0.2	Parkin and PINK1 are required for ubiquitination of MFN-1 and MFN-2. Decreases in MFN-1 and MFN-2 protein levels seen at later timepoints are difficult to interpret as it is unclear whether this is due to degradation by the proteasome and/or loss of whole mitochondria by mitophagy.	SIGNOR-272779
P40763	P23468	0	dephosphorylation	down-regulates activity	0.517	Transfection of wild-type PTPRD resulted in the specific dephosphorylation of STAT3 at tyrosine 705, a residue that must be phosphorylated for STAT3 to be active	SIGNOR-248442
P26358	Q00535	0	phosphorylation	up-regulates	0.358	We report that cyclin-dependent kinases (cdks) 1, 2 and 5 can phosphorylate ser154 of human dnmt1 in vitro. Further evidence of phosphorylation of endogenous dnmt1 at position 154 by cdks is also found in 293 cells treated with roscovitine, a specific inhibitor of cdk1, 2 and 5	SIGNOR-173685
Q00987	Q96AQ6	1	polyubiquitination	down-regulates quantity by destabilization	0.29	. Accordingly, we identified the microtubule-associated HPIP, a positive regulator of oncogenic AKT signaling, as a novel MDM2 substrate. MDM2-dependent HPIP degradation occurs in breast cancer cells on its phosphorylation by the estrogen-activated kinase TBK1.	SIGNOR-272850
P24941	Q02363	1	phosphorylation	down-regulates	0.434	Id2 acts by forming heterodimers that are unable to bind to specific (e-box) dna sequences. Here we show that this activity can be overcome by phosphorylation of a serine residue within a consensus target site for cyclin-dependent kinases (cdks). In vitro, id2 can be phosphorylated by either cyclin e-cdk2 or cyclin a-cdk2_	SIGNOR-46397
Q00535	Q05655	0	phosphorylation	down-regulates activity	0.2	This generates a binding site for the C2 domain of PKCδ, which in turn phosphorylates CDK5 on T77. The resulting dissociation of the CDK5R1/CDK5 complex abolishes the activity of CDK5.	SIGNOR-277386
Q16665	O15054	1	transcriptional regulation	up-regulates quantity by expression	0.266	To this end, we confirm that KDM3A, KDM4B, KDM4C, KDM5B, KDM5C, and KDM62 are direct targets of HIF-1a while extent the list of known targets to KDM2A, KDM2B, KDM4D, KDM5A, and KDM6A. The results demonstrated that majority of the KDMs were similarly induced (KDM2A, KDM2B, KDM3A, KDM4B, KDM4C, KDM4D, KDM5A, KDM5B, KDM5C, KDM6B, and KDM7A) or repressed (KDM NO66 and KDM1A) by both HIF-1a and HIF-2a.	SIGNOR-271571
P33993	Q05086	0	polyubiquitination	down-regulates quantity by destabilization	0.401	The characterization of this interaction in turn led to the discovery that Mcm7 is a substrate for both E6-AP-dependent and -independent ubiquitination and is specifically targeted for degradation by the 26 S proteasome.	SIGNOR-272543
P11217	P15735	0	phosphorylation	up-regulates activity	0.55	It is well-characterized that GP is activated by PhK-mediated serine phosphorylation at Ser-15	SIGNOR-267400
P37840	P25098	0	phosphorylation	down-regulates activity	0.2	We found that grk-mediated phosphorylation inhibits synuclein's interaction with both phospholipids and pld2. These findings suggest that gpcrs may be able to indirectly stimulate pld2 activity via their ability to regulate grk-promoted phosphorylation of synuclein.	SIGNOR-78333
Q8N5V2	P61586	1	guanine nucleotide exchange factor	up-regulates activity	0.675	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-260562
Q13188	Q9NRM7	1	phosphorylation	up-regulates	0.609	Activation of mst1/2 leads to phosphorylation and activation of their direct substrates, lats1/2.	SIGNOR-175801
P98177	P31751	0	phosphorylation	down-regulates activity	0.606	FOXO4 transcription factor, also referred to AFX, contains three putative phosphorylation motif sites for protein kinase B (PKB), Thr32, Ser197, and Ser262, and it is proposed that phosphorylated FOXO4 stays in the cytosol and is imported to the nucleus through dephosphorylation to induce target gene expression.[...]These results indicate that phosphorylation at Thr32 and Ser197 is indispensable, whereas that at Ser262 is not critical, for regulation of the nuclear localization and transcriptional activity of FOXO4	SIGNOR-248055
P06493	Q9UI09	1	phosphorylation	up-regulates activity	0.2	Here, we show that a fraction of cyclin B1/Cdk1 proteins localizes to the matrix of mitochondria and phosphorylates a cluster of mitochondrial proteins, including the complex I (CI) subunits in the respiratory chain. Cyclin B1/Cdk1-mediated CI phosphorylation enhances CI activity, whereas deficiency of such phosphorylation in each of the relevant CI subunits results in impairment of CI function.\|These results were confirmed by generating phosphorylation defective forms of the five CI subunits through substitutions of S/T residues with Alanine (A) on either Cdk1 optimal or minimal consensus motifs (T383 on NDUFV1, S105 on NDUFV3, S364 on NDUFS2, S55/S29/T5 on NDUFB6, and T142/T120 on NDUFA12). The mutation of Cdk1 consensus motifs severely diminished their phosphorylation	SIGNOR-275587
Q9UKV0	Q96GD4	0	phosphorylation	down-regulates	0.262	We define the precise site of aurb-mediated phosphorylation as a conserved serine within the nuclear localization signals of hdac4, hdac5, and hdac9 at ser265, ser278, and ser242, respectivelyduring mitosis, aurb-mediated phosphorylation may localize class iia hdacs to a phosphorylation gradient at the spindle midzone, permitting temporal and spatial regulatory mechanisms altering hdac protein interactions	SIGNOR-198654
P53350	O60260	1	phosphorylation	up-regulates activity	0.2	Parkin Is Phosphorylated by Plk1 at Ser378 and Activated during Mitosis	SIGNOR-276938
Q05655	P63104	1	phosphorylation	down-regulates activity	0.446	We confirmed that MAPKAPK2 interacted with and phosphorylated 14-3-3zeta in vitro and in HEK293 cells. \| Experimentally, S58D mutation significantly impaired both 14-3-3zeta dimerization and binding to Raf-1.	SIGNOR-249222
Q9H4A3	Q15796	1	phosphorylation	up-regulates quantity	0.2	In addition, WNK1 and WNK4 can phosphorylate Smad2, and silencing of WNK1 reduces Smad2 protein levels in HeLa cells, suggesting that WNKs have complex effects on TGFbeta signaling, which itself can promote cancer or act in a tumor suppressing manner.	SIGNOR-280164
P08151	Q13131	0	phosphorylation	down-regulates activity	0.334	AMPK phosphorylates GLI1 at serines 102 and 408 and threonine 1074. Mutation of these three sites into alanine prevents phosphorylation by AMPK. This in turn leads to increased GLI1 protein stability, transcriptional activity, and oncogenic potency.	SIGNOR-259862

P27361

Q05469

1

phosphorylation

up-regulates activity

0.415

Thus, activation of the ERK pathway appears to be able to regulate adipocyte lipolysis by phosphorylating HSL on Ser(600) and increasing the activity of HSL.

SIGNOR-249470

P50750

P50613

0

phosphorylation

up-regulates activity

0.551

Cdk7 activates Cdk9 in vitro .|Cdk7 phosphorylates wild-type Cdk9 on Thr186, resulting in increased activity towards a recombinant GST-Spt5 substrate.

SIGNOR-279455

P18846

P51812

0

phosphorylation

up-regulates activity

0.318

ATF1 and CREB can be phosphorylated by Rsk2 which is a protein kinase directly activated by Erk MAP kinase. These results suggest a signaling pathway in which Erk MAP kinase activates the c-fos enhancer by direct phosphorylation of p62TCF and by activation of Rsk related kinases that phosphorylate ATF1 and CREB.|ATF1 and CREB can be phosphorylated by Rsk2 which is a protein kinase directly activated by Erk MAP kinases.

SIGNOR-280117

Q8N752

P10071

1

phosphorylation

up-regulates

0.333

Ci is phosphorylated by pka at multiple sites priming phosphorylation by both gsk3 and cki, leading to partial proteolysis. The pka, gsk3, and cki sites are conserved in gli2 and gli3, vertebrate homologs of ci that are similarly processed

SIGNOR-144554

P16220

Q6SA08

0

phosphorylation

up-regulates

0.578

Tssk5, a novel member of the testis-specific serine/threonine kinase family, phosphorylates creb at ser-133, and stimulates the cre/creb responsive pathway.

SIGNOR-138289

P07947

Q969T9

1

phosphorylation

up-regulates activity

0.304

Using dominant-negative, constitutively active mutants, RNAi, and pharmacological studies, we demonstrated that phosphorylation of WBP2 at Tyr192 and Tyr231 could be regulated by c-Src and c-Yes kinases.We further showed that abrogating WBP2 phosphorylation impaired >60% of ERα reporter activity, putatively by blocking nuclear entry of WBP2 and its interaction with ERα.

SIGNOR-273582

P19544

O60500

1

transcriptional regulation

up-regulates quantity by expression

0.487

The Wilms tumor suppressor gene (WT1) is a zinc-finger-containing transcription factor that is coexpressed with NPHS1 in differentiated podocytes; gel shift binding assays demonstrate that a recombinant WT1 protein can bind and activate the 186-bp NPHS1 fragment in a sequence-specific manner

SIGNOR-252299

P45983

Q13526

1

phosphorylation

up-regulates quantity by stabilization

0.272

Mechanistically, the JNK kinases directly bind to and phosphorylate PIN1 at Ser115, and this phosphorylation prevents PIN1 mono-ubiquitination at Lys117 and its proteasomal degradation.

SIGNOR-277562

P63000

Q9H0H5

0

gtpase-activating protein

down-regulates activity

0.586

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-260512

Q05397

Q13164

0

phosphorylation

up-regulates activity

0.291

Remarkably, the reduction in ERK5 expression correlated with decreased p-FAK(Tyr397) staining, consistent with the requirement of ERK5 for mediating FAK activation in vivo (Fig. 6C).|We confirmed that JWG-045, a novel pharmacological inhibitor of ERK5 exhibiting significantly reduced affinity for BRD4 compared with XMD8-92 (25, 26), did not suppress FAK phosphorylation at Tyr397 in MDA-MB-231 cells (Supplementary Fig. S3B and C).

SIGNOR-279304

Q13480

P12931

0

phosphorylation

up-regulates

0.704

Using both mutagenesis and mass spectrometry approaches, y242, y259, y317, y373 and y627 of gab1 were identified to be phosphorylated by c-src a gab1 mutant with substitutions of the src phosphorylation sites failed to promote hgf-induced dna synthesis

SIGNOR-236314

P27361

Q92934

1

phosphorylation

down-regulates

0.483

Erk-1 map kinase prevents tnf-induced apoptosis through bad phosphorylation and inhibition of bax translocation in hela cells.

SIGNOR-188172

P68400

Q00613

1

phosphorylation

up-regulates activity

0.37

Transcriptional activity and DNA binding of heat shock factor-1 involve phosphorylation on threonine 142 by CK2.

SIGNOR-250898

O14974

P04049

0

phosphorylation

down-regulates activity

0.274

In hESC, Raf-1 directly phosphorylates and inactivates MYPT1, and this process requires kinase active Raf-1 protein.

SIGNOR-278979

P23396

P06493

0

phosphorylation

up-regulates

0.362

These results suggest that the phosphorylation of rps3 by cdk1 occurs at thr221 during g2/m phase and, moreover, that this event is important for nuclear accumulation of rps3.

SIGNOR-176131

P36956

O75874

1

transcriptional regulation

up-regulates quantity by expression

0.282

IDH1 gene transcription is sterol regulated and activated by SREBP-1a and SREBP-2 in human hepatoma HepG2 cells|evidence that IDH1 may regulate lipogenesis in hepatic cells

SIGNOR-253132

O95096

Q8TAM6

1

transcriptional regulation

up-regulates quantity by expression

0.249

Further study revealed that Nkx2.2 could bind JN promoter and its overexpression increase the promoter activity of JN.

SIGNOR-268965

P06493

P06400

1

phosphorylation

down-regulates

0.688

The retinoblastoma gene product (prb) is a nuclear phosphoprotein that is thought to play a key role in the negative regulation of cellular proliferation. The active form of prb is underphosphorylated. Using synthetic peptides corresponding to potential cdc2 phosphorylation sites, we have developed a strategy which has allowed the identification of five sites. S249, t252, t373, s807 and s811 are phosphorylated in vivo, and in each case these sites correspond closely to the consensus sequence for phosphorylation by p34cdc2.

SIGNOR-21564

O14757

P19838

1

phosphorylation

down-regulates

0.275

Taken together, the above findings suggest that chk1 phosphorylates p50 at s329 and further, that this phosphorylation blocks p50 dna binding.

SIGNOR-195208

P17252

Q96QS3

1

phosphorylation

up-regulates activity

0.2

We confirm that ARX is phosphorylated by PRKCA and demonstrate phosphorylation at serine 174. We demonstrate that phosphorylation is required for correct transcriptional activity of the ARX protein using transcriptome-wide analysis of gene expression of phospho-null mutants (alanines replacing serines) compared to ARX wild-type (ARX-WT) overexpressed in pancreatic alpha TC cells.

SIGNOR-277418

O43426

Q9P286

0

phosphorylation

up-regulates activity

0.2

We identified two novel Pak5 substrates, Pacsin1 and Synaptojanin1, proteins that directly interact with one another to regulate synaptic vesicle endocytosis and recycling. Pacsin1 and Synaptojanin1 were phosphorylated by Pak5 and the other group II Paks in vitro, and Pak5 phosphorylation promoted Pacsin1-Synaptojanin1 binding both in vitro and in vivo.

SIGNOR-263026

P27361

Q93045

1

phosphorylation

down-regulates activity

0.352

SCG10, a growth cone-enriched MT-destabilizing protein, has been recently characterized as an in vitro substrate for various serine/threonine kinases including PKA, MAP kinase, and CDK (19). We have found that SCG10 is phosphorylated in vivo in developing rat brain.| The sites for MAP kinase phosphorylation were identified as Ser-62 and Ser-73 of SCG10|By expressing a series of phosphorylation site mutants, we showed that the MT-destabilizing effect of SCG10 could be modulated. While the nonphosphorylatable mutant showed higher activity than the wild-type protein, the activity of the mutant in which phosphorylation on all four sites was mimicked by an aspartate residue was greatly reduced. These data suggest that the nonphosphorylated state of SCG10 represents the most active form of the protein.

SIGNOR-249115

Q13489

Q86VP3

1

polyubiquitination

down-regulates quantity by destabilization

0.286

Under basal conditions, PACS-2 underwent K48-linked poly-ubiquitination, resulting in PACS-2 proteasomal degradation. Biochemical assays showed cIAP-1 and cIAP-2 interacted with PACS-2 in vitro and co-immunoprecipitation studies demonstrated that the two cIAPs bound PACS-2 in vivo. More importantly, both cIAP-1 and cIAP-2 directly mediated PACS-2 ubiquitination in a cell-free assay.

SIGNOR-272852

P04629

Q13191

0

ubiquitination

down-regulates quantity

0.276

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

SIGNOR-278690

P08246

P25116

1

cleavage

up-regulates activity

0.43

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.|Protease-activated receptors (PARs) mediate cell activation after proteolytic cleavage of their extracellular amino terminus.|Protease-activated receptors (PARs) mediate cell activation after proteolytic cleavage of their extracellular amino terminus

SIGNOR-263565

P25963

Q9UHD2

0

phosphorylation

down-regulates quantity by destabilization

0.456

Nuclear factor-kappaB activation depends on phosphorylation and degradation of its inhibitor protein, IkapapB. TBK-1 and IKK-i phosphorylate Ser36 of IkappaBalpha.

SIGNOR-246643

O60500

P12931

0

phosphorylation

up-regulates activity

0.48

Inhibition of Src kinase dependent Nephrin phosphorylation achieved by incubation of WT-Nephrin-overexpressing cells with 1 mum PP2 abolished the positive effect of Nephrin on GSIR (XREF_FIG D).|We were able to demonstrate a complete prevention of Nephrin phosphorylation, confirming that Nephrin phosphorylation is mediated by Src.

SIGNOR-280129

P42768

P06241

0

phosphorylation

up-regulates activity

0.561

As shown in XREF_FIG F, Fyn immunoprecipitates from activated T cells induced the tyrosine phosphorylation of WASp, but neither WASpDeltaPro nor WASpY291F mutant proteins were phosphorylated in this assay.

SIGNOR-279333

P48729

O75581

1

phosphorylation

up-regulates

0.552

We show that wnt induces sequential phosphorylation of lrp6 by gsk3 and casein kinase 1, and this dual phosphorylation promotes the engagement of lrp6 with the scaffolding protein axin.Site ii, like site i, was phosphorylated, as detected by means of a phospho-specific antibody (ab1493, for phosphorylated t1493 in lrp6)

SIGNOR-143034

P54756

Q14938

0

transcriptional regulation

up-regulates quantity

0.2

For example, within the NFI targetome, we identified 6 collagen genes, 13 genes encoding potassium channel or glutamate receptor subunits and a range of factors related to axon guidance (e.g. Slit1, Robo1, Epha4, Epha5, Epha8)

SIGNOR-268909

P06213

P23467

0

dephosphorylation

down-regulates

0.344

Identification of tyrosine phosphatases that dephosphorylate the insulin receptor.

SIGNOR-75997

Q9HCE7

Q13873

1

ubiquitination

down-regulates

0.56

Smurf1 and smurf2 are e3 ubiquitin ligases known to suppress tgf-beta signaling through degradation of smads and receptors for tgf-beta and bmps.

SIGNOR-153402

P12931

Q13177

1

phosphorylation

up-regulates

0.562

Pak2 became tyrosine phosphorylated in its n-terminal regulatory domain, where y130 was identified as the major phosphoacceptor site. Tyrosine phosphorylation-mediated superactivation of pak2 could be induced by overexpression of different src kinases or by inhibiting cellular tyrosine phosphatases with pervanadate and could be blocked by the src kinase inhibitor pp1 or by mutating the y130 residue.

SIGNOR-92460

Q96LC9

P28482

0

phosphorylation

up-regulates

0.253

Phosphomimetic mutation of this site (s74d) moderately enhanced bmf apoptotic activity in vivo.22 here, we demonstrate a previously unrecognized mode of regulation of bmf. We show that b-raf-mek-erk2 signaling regulates bmf phosphorylation at serine 74 and serine 77. Phosphorylation of serine 77 downregulates the pro-apoptotic activity of bmf.

SIGNOR-195475

O60674

Q99683

1

phosphorylation

down-regulates quantity by destabilization

0.367

Furthermore, JAK2, but not JAK1, directly bound to and phosphorylated ASK1 at Tyr-718, leading to an enhanced association of ASK1 with SOCS1 and subsequent ASK1 degradation.

SIGNOR-276145

Q9BZL6

Q02156

0

phosphorylation

up-regulates

0.2

In cells transfected with pkc? Or pkc? The phosphorylation of ser876 was markedly more pronounced than the phosphorylation of ser706/ser710 / the phosphorylation of ser706/ser710 in pkd2 reflects the activation of the kinase.

SIGNOR-89415

O96013

P35222

1

phosphorylation

up-regulates

0.286

Pak4 interacts with and phosphorylates _-catenin on ser675, which promotes the tcf/lef transcriptional activity and stabilizes _-catenin through inhibition of its degradation.

SIGNOR-191557

P06400

P05771

0

phosphorylation

down-regulates activity

0.352

The exact mechanism by which PKCbeta degrades RB is unknown.|To attribute increased RB phosphorylation specifically to PKC\u03b2, we transiently transfected PKC\u03b2 -/- hepatocytes, and reintroduction of PKC\u03b2 specifically resulted in increased in phospho-RB (Ser780) levels, further supporting that PKC\u03b2 phosphorylates RB specifically at Ser780 without affecting phosphorylation at other residues (Ser807 and Ser811) (Figure xref ).

SIGNOR-280083

P53041

Q9UPZ9

1

dephosphorylation

down-regulates activity

0.2

MAK and MRK require dual phosphorylation in a TDY motif catalyzed by an unidentified human threonine kinase and tyrosine autophosphorylation.| Protein phosphatase 5 (PP5) interacts with MRK in a complex and dephosphorylates MRK at T157 in vitro and in situ.

SIGNOR-248541

P12931

Q9UQB3

1

phosphorylation

up-regulates activity

0.329

Furthermore, according to our data from immunoprecipitation to py20 antibody, c-Src can phosphorylate delta-catenin on Y1073, Y1176, Y1179 and Y1112, with the predominant sites being Y1073, Y1112 and Y1176.|Interestingly, we found that c-Src can increase the stability of delta-catenin in MEF cells.

SIGNOR-278327

Q06124

P42224

1

dephosphorylation

down-regulates activity

0.743

SHP-2 is a dual-specificity phosphatase involved in Stat1 dephosphorylation at both tyrosine and serine residues in nuclei|In SHP-2-/- mouse fibroblast cells, Stat1 phosphorylation at both the tyrosine residue Tyr(701) and the serine residue Ser(727) |Overexpression of SHP-2 in 293T cells inhibited IFNgamma-dependent Stat1 phosphorylation and suppressed Stat1-dependent induction of luciferase activity.

SIGNOR-248673

Q9UPW6

Q9C0K0

1

transcriptional regulation

down-regulates quantity

0.495

Satb2 represses the transcription of Nr4a2. The misexpression of Nr4a2 together with Ctip2 induces expression of SubC-specific genes in wild-type Rsp, and simultaneous knockdown of these two genes in Rsp Satb2-mutant cells prevents their fate transition to SubC identity. Thus, Satb2 serves as a determinant gene in the Rsp regionalization by repressing Nr4a2 and Ctip2 during cortical development

SIGNOR-268931

Q9BYB0

Q15398

0

relocalization

up-regulates activity

0.2

SHANK proteins are ‘master’ scaffolding proteins that tether and organize intermediate scaffolding proteins. They are located at excitatory synapses, where they are crucial for proper synaptic development and function. SAPAP proteins subsequently bind to the PDZ domain of members of the SHANK protein family. SHANK proteins then bind to the actin cytoskeleton and to Homer protein, which in turn interacts with mGluRs. Through these extended links, PSD95, SAPAP, SHANK and Homer proteins form a quaternary complex that brings together mGluR and NMDAR complexes in the PSD (FIG. 3).

SIGNOR-264600

O95747

Q9H4A3

0

phosphorylation

up-regulates

0.484

Activation of wnk1 coincides with the phosphorylation and activation of two wnk1 substrates, namely, the protein kinases ste20/sps1-related proline alanine-rich kinase (spak) and oxidative stress response kinase-1 (osr1)

SIGNOR-151659

Q9NWF9

O00206

1

ubiquitination

down-regulates quantity by destabilization

0.388

Here we describe how a RING finger protein, Triad3A, acts as an E3 ubiquitin-protein ligase and enhances ubiquitination and proteolytic degradation of some TLRs. Triad3A overexpression promoted substantial degradation of TLR4 and TLR9 with a concomitant decrease in signaling, but did not affect TLR2 expression or signaling.

SIGNOR-271504

Q12834

Q9UHD2

0

phosphorylation

down-regulates activity

0.2

It was found that TBK1 phosphorylates both Cdc20 as well as Cdh1 (Figure 2F).

SIGNOR-279766

Q9ULV5

P52564

0

phosphorylation

up-regulates activity

0.2

Regulation of Hsf4b nuclear translocation and transcription activity by phosphorylation at threonine 472| At the upstream, MEK6 was found to interact with Hsf4b and enhance Hsf4b's nuclear translocation and transcription activity, probably by phosphorylation at sites such as T472. Taken together, our results suggest that phosphotylation of Hsf4b at T472 by protein kinases such as MEI

SIGNOR-275493

P01019

P08311

0

cleavage

up-regulates activity

0.643

Cathepsin G, elastase, and proteinase 3 are serine proteinases released by activated neutrophils. Cathepsin G can cleave angiotensinogen to release angiotensin II, but this activity has not been previously reported for elastase or proteinase 3. In this study we show that elastase and proteinase 3 can release angiotensin I from angiotensinogen and release angiotensin II from angiotensin I and angiotensinogen.

SIGNOR-256312

P06493

Q8NEB9

1

phosphorylation

down-regulates

0.42

We show that vps34 is phosphorylated on thr159 by cdk1, thr159 phosphorylation negatively regulates the ptdins3 kinase activity of vps34 and autophagy

SIGNOR-165768

Q06187

P05771

0

phosphorylation

down-regulates activity

0.382

We provide direct evidence that PKCbeta acts as a feedback loop inhibitor of Btk activation. Inhibition of PKCbeta results in a dramatic increase in B-cell receptor (BCR)-mediated Ca2+ signaling. We identified a highly conserved PKCbeta serine phosphorylation site in a short linker within the Tec homology domain of Btk. Mutation of this phosphorylation site led to enhanced tyrosine phosphorylation and membrane association of Btk, and augmented BCR and FcepsilonRI-mediated signaling in B and mast cells, respectively. | This deductive analysis indicated that PKCbeta phosphorylates S180 in the region bisecting the Btk motif (BM) and the PRR of the TH domain.

SIGNOR-249110

P08575

P06241

1

dephosphorylation

up-regulates activity

0.73

On the membrane SKAP55, via its phosphorylated Tyr-271, further binds the SH2 domain of Fyn to replace the low-affinity bound inhibitory site of the kinase. Consequently, CD45 may have transiently disassociated with the Tyr-232 residue of SKAP55 through dephosphorylation and simultaneously interacted with the released the phosphorylated inhibitory tyrosine residue of Fyn for dephosphorylation, resulting in activation of the Src family kinase Fyn and initiation of TCR-engaged signal transduction.

SIGNOR-248352

P42574

Q4V328

1

cleavage

up-regulates activity

0.414

These results suggest that the region of GRASP‐1 downstream of the Caspase‐3‐cleavage site is capable of activating the JNK signaling pathway by enhancing the phosphorylation of JNK. these results suggest that full length GRASP‐1 does not enhance JNK pathway activity, possibly due to the inhibitory effect of the N‐terminal fragment on the C‐terminal fragment. In contrast, Caspase‐3 cleavage of GRASP‐1 releases the C‐terminal fragment, which in turn activates JNK signaling by serving as a scaffold protein.

SIGNOR-260641

P41161

O00712

0

transcriptional regulation

down-regulates quantity

0.2

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

SIGNOR-268880

O60260

O95140

1

ubiquitination

down-regulates quantity

0.2

Parkin and PINK1 are required for ubiquitination of MFN-1 and MFN-2. Decreases in MFN-1 and MFN-2 protein levels seen at later timepoints are difficult to interpret as it is unclear whether this is due to degradation by the proteasome and/or loss of whole mitochondria by mitophagy.

SIGNOR-272780

P16070

P17612

0

phosphorylation

up-regulates

0.2

Pka can phosphorylate ser316 directly cd44 s291a and s316a mutants may disrupt downstream signalling events by displacing endogenous cd44 from plasma membrane microdomains.

SIGNOR-147208

Q96EP1

Q96GM5

1

polyubiquitination

down-regulates quantity by destabilization

0.307

Here we report that CHFR interacts with BRG1, SNF5, and BAF60a of the SWI/SNF-like BAF complex and ubiquitinates them to target for degradation through a proteasome-mediated pathway, and that SRG3/mBAF155 stabilizes these components by blocking their interaction with CHFR. These results suggest that CHFR enhances the degradation of the components of the SWI/SNF-like BAF complex by inducing their poly-ubiquitination.

SIGNOR-271459

P12931

P17655

1

phosphorylation

up-regulates activity

0.525

CAPN2 itself was a bone fide substrate of SRC that was primarily phosphorylated at Y625 by SRC and exhibited increased proteolysis activity upon phosphorylation.

SIGNOR-277598

P68400

P30305

1

phosphorylation

up-regulates activity

0.338

Mass spectrometry analysis demonstrates that at least two serine residues, Ser-186 and Ser-187, are phosphorylated in vivo. | Finally, we demonstrate that phosphorylation of CDC25B by protein kinase CK2 increases the catalytic activity of the phosphatase in vitro as well as in vivo.

SIGNOR-250836

Q99986

Q05655

0

phosphorylation

down-regulates activity

0.285

PKC\u03b4 phosphorylates VRK1 on Ser-355 in vitro.|PKCdelta negatively regulates VRK1 kinase activity in vitro.

SIGNOR-278219

P17612

P15924

1

phosphorylation

down-regulates activity

0.328

HeLa cells treated with forskolin indicated that stimulation of protein kinase A in transfected cells could decrease the interaction of DP.AN.SerC23 with keratin IF networks. phosphorylation of Ser-C23 could destabilize interactions that occur either directly through this 20 residue sequence or that are dependent on its correct conformation

SIGNOR-250353

P49841

Q9BZS1

1

phosphorylation

down-regulates quantity by destabilization

0.285

Our previous study showed, by mass spectrometry analysis, that GSK-3β phosphorylates Foxp3 at Ser270 and Ser275

SIGNOR-277245

Q9Y252

P53667

1

polyubiquitination

down-regulates quantity by destabilization

0.432

Consistent with a role in axonal growth, we found that Rnf6 binds to, polyubiquitinates, and targets LIMK1 for proteasomal degradation in growth cones of primary hippocampal neurons.

SIGNOR-271481

Q5SGD2

O75460

1

dephosphorylation

up-regulates activity

0.309

Overall, our study establishes that PP2Ce mediated IRE1 regulation in ER stress signaling is a potentially important molecular basis for its genetic contribution to metabolic syndrome.Lin et al. [36] have reported that different durations and composition of ER stress signaling pathways can dictate cell fate and the balance between survival and death.|Recombinant wildtype PP2Ce, but not a phosphatase-dead mutant (PP2Ce-D302A), effectively dephosphorylated the phosphor-Ser724 site of IRE1\u03b1 protein (p-IRE1\u03b1) (A).

SIGNOR-277074

P36507

P27361

1

phosphorylation

up-regulates

0.742

The primary structure of mek, a protein kinase that phosphorylates the erk gene product

SIGNOR-19244

Q8NEZ5

P04637

1

ubiquitination

down-regulates quantity by destabilization

0.338

We demonstrate here that SCFFbxo22-KDM4A is a senescence-associated E3 ligase targeting methylated p53 for degradation. We find that Fbxo22 is highly expressed in senescent cells in a p53-dependent manner, and that SCFFbxo22 ubiquitylated p53 and formed a complex with a lysine demethylase, KDM4A. |SCFFbxo22 forms a ternary complex with p53 and KDM4A that targets methylated p53 for degradation.

SIGNOR-273448

P36894

O15198

1

phosphorylation

up-regulates activity

0.706

To ascertain whether overexpression of BMPr1A can initiate adipocyte lineage commitment in the absence of its BMP ligand, constitutively active (CA)-BMPr1A and CA-BMPr1B were expressed in C3H10T1/2 stem cells using a mouse stem cell virus (MSCV) retroviral system. […]Thus, their overexpression provoked a substantial rise in the phosphorylation of Smad1/5/8 and p38 MAPK, known downstream phosphorylated intermediates in the BMP signaling pathway.

SIGNOR-255772

P35813

P50750

1

dephosphorylation

down-regulates activity

0.493

Taken together, our data indicate that PPM1A and to some extent PPM1B are important negative regulators of P-TEFb function

SIGNOR-248490

P17252

P15172

1

phosphorylation

down-regulates activity

0.363

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

SIGNOR-248845

O00141

P21796

1

phosphorylation

down-regulates quantity

0.2

As hypothesized based upon our observation that activated SGK-1 reduces VDAC-1 protein levels, sgk-1 overexpression normalizes the shortened lifespan of vdac-1 transgenics .|Taken together, these data indicate that Ser104 phosphorylation of VDAC1 by SGK1 increases its ubiquitination and subsequent cellular clearance.

SIGNOR-278988

Q16566

Q8N5S9

0

phosphorylation

up-regulates

0.62

Phosphorylation of ca(2+)/cam-bound camkiv on its activation loop threonine (residue thr(200) in human camkiv) by ca(2+)/calmodulin-dependent kinase kinase leads to increased camkiv kinase activity.

SIGNOR-134649

Q9BXL7

P62714

0

dephosphorylation

down-regulates activity

0.2

NF-kappaB activation is triggered by PKCtheta-dependent phosphorylation of Carma1 after TCR/CD28 co-stimulation. PKCtheta-phosphorylated Carma1 was suggested to function as a molecular scaffold that recruits preassembled Bcl10-Malt1 complexes to the membrane|we demonstrate that PP2A removes PKCtheta-dependent phosphorylation of Ser645 in Carma1, and show that maintenance of this phosphorylation is correlated with increased T-cell activation.

SIGNOR-248607

P30411

P43250

0

phosphorylation

down-regulates activity

0.288

Ligand-induced phosphorylation is found at Ser339 and Ser346/Ser348 that could be executed by several G protein-coupled receptor kinases. 32P labeling of peptide 3 containing pS346/pS348 was enhanced 1.5–3-fold as compared with mock-transfected cells in the order GRK6 < GRK5 < GRK2 < GRK4α < GRK3. several endogenous GRKs may phosphorylate the B2R and that the various GRKs, even without apparent effect on total GPCR phosphorylation levels, may induce distinct phosphorylation patterns with possible functional consequences for receptor desensitization and sequestration.

SIGNOR-251207

P49840

Q96RR4

1

phosphorylation

down-regulates

0.269

Cdk5 and gsk3 phosphorylate ser-129, ser-133, and ser-137. Mutation of ser-129, ser-133, and ser-137 increases autonomous activity with little change in ca2 /cam-dependent activity.

SIGNOR-198122

P17612

Q9NR82

1

phosphorylation

up-regulates activity

0.2

We conclude that phosphorylation of S53 on the amino terminus of Kv7.5 is essential for PKA-dependent enhancement of channel activity in response to βAR activation in vascular and airway smooth muscle cells.

SIGNOR-265980

O60729

Q9NQR1

1

dephosphorylation

down-regulates quantity by destabilization

0.2

The dephosphorylation of S29 during late mitosis by the Cdc14 phosphatases was required for APC(cdh1)-mediated ubiquitination of PR-Set7 and subsequent proteolysis.

SIGNOR-248339

Q9Y5S8

P05771

0

phosphorylation

up-regulates activity

0.2

Site-directed mutagenesis and isothermal titration calorimetry indicated that protein kinase C-beta1 phosphorylates Nox1 at threonine 429. Moreover, Nox1 threonine 429 phosphorylation facilitated the association of Nox1 with the NoxA1 activation domain and was necessary for NADPH oxidase complex assembly

SIGNOR-264729

P42229

Q9P1W9

1

transcriptional regulation

up-regulates quantity by expression

0.41

The results of 2 microarray experiments demonstrated that the aberrant activation of STAT proteins by Flt3-ITDs resulted in the up-regulation of several STAT5-responsive genes, such as Pim-1, Pim-2, and members of the SOCS (suppressor of cytokine signaling) protein family. These results are particularly interesting because recent data point to an important role of Pim kinases in the antiapoptosis of hematopoietic cells.

SIGNOR-249622

P25963

Q15418

0

phosphorylation

up-regulates activity

0.386

Mitogen activated ribosomal S6 kinase (p90 rsk1) phosphorylates IkappaBalpha at S32, binds IkappaBalpha in vivo, and overexpression of dominant negative p90 rsk1 inhibits degradation of IkappaBalpha in response to TPA.

SIGNOR-279311

Q9UHD2

Q04759

0

phosphorylation

up-regulates activity

0.2

TBKBP1 recruits TBK1 to protein kinase C-theta (PKCθ) through a scaffold protein, CARD10. This enables PKCθ to phosphorylate TBK1 at Ser 716, a crucial step for TBK1 activation

SIGNOR-272472

P08069

O15530

1

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

P48729

O14503

1

phosphorylation

down-regulates quantity by destabilization

0.2

CK1α-mediated phosphorylation of DEC1 on a conserved degron is required for DEC1 degradation.

SIGNOR-276851

Q8IWA4

O60260

0

ubiquitination

down-regulates quantity

0.2

Parkin and PINK1 are required for ubiquitination of MFN-1 and MFN-2. Decreases in MFN-1 and MFN-2 protein levels seen at later timepoints are difficult to interpret as it is unclear whether this is due to degradation by the proteasome and/or loss of whole mitochondria by mitophagy.

SIGNOR-272779

P40763

P23468

0

dephosphorylation

down-regulates activity

0.517

Transfection of wild-type PTPRD resulted in the specific dephosphorylation of STAT3 at tyrosine 705, a residue that must be phosphorylated for STAT3 to be active

SIGNOR-248442

P26358

Q00535

0

phosphorylation

up-regulates

0.358

We report that cyclin-dependent kinases (cdks) 1, 2 and 5 can phosphorylate ser154 of human dnmt1 in vitro. Further evidence of phosphorylation of endogenous dnmt1 at position 154 by cdks is also found in 293 cells treated with roscovitine, a specific inhibitor of cdk1, 2 and 5

SIGNOR-173685

Q00987

Q96AQ6

1

polyubiquitination

down-regulates quantity by destabilization

0.29

. Accordingly, we identified the microtubule-associated HPIP, a positive regulator of oncogenic AKT signaling, as a novel MDM2 substrate. MDM2-dependent HPIP degradation occurs in breast cancer cells on its phosphorylation by the estrogen-activated kinase TBK1.

SIGNOR-272850

P24941

Q02363

1

phosphorylation

down-regulates

0.434

Id2 acts by forming heterodimers that are unable to bind to specific (e-box) dna sequences. Here we show that this activity can be overcome by phosphorylation of a serine residue within a consensus target site for cyclin-dependent kinases (cdks). In vitro, id2 can be phosphorylated by either cyclin e-cdk2 or cyclin a-cdk2_

SIGNOR-46397

Q00535

Q05655

0

phosphorylation

down-regulates activity

0.2

This generates a binding site for the C2 domain of PKCδ, which in turn phosphorylates CDK5 on T77. The resulting dissociation of the CDK5R1/CDK5 complex abolishes the activity of CDK5.

SIGNOR-277386

Q16665

O15054

1

transcriptional regulation

up-regulates quantity by expression

0.266

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

SIGNOR-271571

P33993

Q05086

0

polyubiquitination

down-regulates quantity by destabilization

0.401

The characterization of this interaction in turn led to the discovery that Mcm7 is a substrate for both E6-AP-dependent and -independent ubiquitination and is specifically targeted for degradation by the 26 S proteasome.

SIGNOR-272543

P11217

P15735

0

phosphorylation

up-regulates activity

0.55

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

SIGNOR-267400

P37840

P25098

0

phosphorylation

down-regulates activity

0.2

We found that grk-mediated phosphorylation inhibits synuclein's interaction with both phospholipids and pld2. These findings suggest that gpcrs may be able to indirectly stimulate pld2 activity via their ability to regulate grk-promoted phosphorylation of synuclein.

SIGNOR-78333

Q8N5V2

P61586

1

guanine nucleotide exchange factor

up-regulates activity

0.675

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-260562

Q13188

Q9NRM7

1

phosphorylation

up-regulates

0.609

Activation of mst1/2 leads to phosphorylation and activation of their direct substrates, lats1/2.

SIGNOR-175801

P98177

P31751

0

phosphorylation

down-regulates activity

0.606

FOXO4 transcription factor, also referred to AFX, contains three putative phosphorylation motif sites for protein kinase B (PKB), Thr32, Ser197, and Ser262, and it is proposed that phosphorylated FOXO4 stays in the cytosol and is imported to the nucleus through dephosphorylation to induce target gene expression.[...]These results indicate that phosphorylation at Thr32 and Ser197 is indispensable, whereas that at Ser262 is not critical, for regulation of the nuclear localization and transcriptional activity of FOXO4

SIGNOR-248055

P06493

Q9UI09

1

phosphorylation

up-regulates activity

0.2

Here, we show that a fraction of cyclin B1/Cdk1 proteins localizes to the matrix of mitochondria and phosphorylates a cluster of mitochondrial proteins, including the complex I (CI) subunits in the respiratory chain. Cyclin B1/Cdk1-mediated CI phosphorylation enhances CI activity, whereas deficiency of such phosphorylation in each of the relevant CI subunits results in impairment of CI function.|These results were confirmed by generating phosphorylation defective forms of the five CI subunits through substitutions of S/T residues with Alanine (A) on either Cdk1 optimal or minimal consensus motifs (T383 on NDUFV1, S105 on NDUFV3, S364 on NDUFS2, S55/S29/T5 on NDUFB6, and T142/T120 on NDUFA12). The mutation of Cdk1 consensus motifs severely diminished their phosphorylation

SIGNOR-275587

Q9UKV0

Q96GD4

0

phosphorylation

down-regulates

0.262

We define the precise site of aurb-mediated phosphorylation as a conserved serine within the nuclear localization signals of hdac4, hdac5, and hdac9 at ser265, ser278, and ser242, respectivelyduring mitosis, aurb-mediated phosphorylation may localize class iia hdacs to a phosphorylation gradient at the spindle midzone, permitting temporal and spatial regulatory mechanisms altering hdac protein interactions

SIGNOR-198654

P53350

O60260

1

phosphorylation

up-regulates activity

0.2

Parkin Is Phosphorylated by Plk1 at Ser378 and Activated during Mitosis

SIGNOR-276938

Q05655

P63104

1

phosphorylation

down-regulates activity

0.446

We confirmed that MAPKAPK2 interacted with and phosphorylated 14-3-3zeta in vitro and in HEK293 cells. | Experimentally, S58D mutation significantly impaired both 14-3-3zeta dimerization and binding to Raf-1.

SIGNOR-249222

Q9H4A3

Q15796

1

phosphorylation

up-regulates quantity

0.2

In addition, WNK1 and WNK4 can phosphorylate Smad2, and silencing of WNK1 reduces Smad2 protein levels in HeLa cells, suggesting that WNKs have complex effects on TGFbeta signaling, which itself can promote cancer or act in a tumor suppressing manner.

SIGNOR-280164

P08151

Q13131

0

phosphorylation

down-regulates activity

0.334

AMPK phosphorylates GLI1 at serines 102 and 408 and threonine 1074. Mutation of these three sites into alanine prevents phosphorylation by AMPK. This in turn leads to increased GLI1 protein stability, transcriptional activity, and oncogenic potency.

SIGNOR-259862