GleghornLab/Signor_processed · Datasets at Hugging Face

IdA stringlengths 6 21	IdB stringlengths 6 21	labels float64 0 2	mechanism stringclasses 40 values	effect stringclasses 10 values	score float64 0.1 0.99 ⌀	sentence stringlengths 10 1.63k ⌀	signor_id stringlengths 12 14
Q13950	P46531	1	binding	down-regulates	0.38	Runx2 is an inhibitor of the notch1 signaling pathway during normal osteoblast differentiation. The n-terminal domain of runx2 was crucial to the binding and inhibition of the the n-terminus of the notch1 intracellular domain.	SIGNOR-167627
Q9Y3L3	P63000	1	gtpase-activating protein	down-regulates activity	0.38	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-260514
Q9H2X6	Q9P1Z0	1	phosphorylation	down-regulates activity	0.379	The human protein kinase HIPK2 phosphorylates and downregulates the methyl-binding transcription factor ZBTB4.	SIGNOR-262882
P68400	P52655	1	phosphorylation	up-regulates activity	0.379	We now show that human TFIIA is phosphorylated in vivo on serine residues that are partially conserved between yeast and human TFIIA large subunits. Alanine substitution mutation of serine residues 316 and 321 in TFIIA alphabeta reduced TFIIA phosphorylation significantly in vivo. Additional alanine substitutions at serines 280 and 281 reduced phosphorylation to undetectable levels. Mutation of all four serine residues reduced the ability of TFIIA to stimulate transcription in transient transfection assays with various activators and promoters, indicating that TFIIA phosphorylation is required globally for optimal function.	SIGNOR-250877
P14778	P45983	1	phosphorylation	up-regulates activity	0.379	Il-1 binding to its receptor triggers a cascade of signaling events, including activation of the stress-activated mitogen-activated protein (map) kinases, c-jun nh2-terminal kinase (jnk) and p38 map kinase, as well as transcription factor nuclear factor kappab (nf-kappab	SIGNOR-249513
O75056	P46531	1	binding	up-regulates activity	0.379	Furthermore, we show that Syndecan-3 interacts with Notch and is required for Notch processing by ADAM17/tumor necrosis factor-converting enzyme (TACE) and signal transduction. Together, our data support the conclusion that Syndecan-3 and Notch cooperate in regulating homeostasis of the satellite cell population and myofiber size.	SIGNOR-244072
P00519	Q92918	1	phosphorylation	up-regulates activity	0.379	C-Abl phosphorylates HPK1 in cytoplasm and stimulates HPK1 activity. the c-Abl phosphorylation site (YXXP) in HPK1 (Y232QPP; aa 232–235) is localized in HPK1-KD	SIGNOR-251429
Q9UIJ5	P78352	1	palmitoylation	up-regulates activity	0.379	Plasma membrane targeting of DHHC2 palmitoyltransferase rapidly recruited PSD-95 to the plasma membrane and proved essential for postsynaptic nanodomain formation.	SIGNOR-261290
P53350	O60563	1	phosphorylation	down-regulates activity	0.379	Further analysis indicated that Plk1 could phosphorylate cyclin T1 at Ser564 and inhibit the kinase activity of cyclin T1/Cdk9 complex on phosphorylation of the C-terminal domain (CTD) of RNA polymerase II.	SIGNOR-276501
Q5S007	P31749	1	phosphorylation	up-regulates	0.379	Expression of wild-type LRRK2 promoted neuronal survival against apoptosis through activation of the downstream effector, Akt by phosphorylation of Ser473. Phosphorylated Akt in turn inhibited FOXO 1 signaling	SIGNOR-252598
P67870	P55010	1	phosphorylation	up-regulates activity	0.379	Mass spectrometric analysis of maximally in vitro phosphorylated eIF5 localized the major phosphorylation sites at Ser-387 and Ser-388 near the C-terminus of eIF5. These serine residues are embedded within a cluster of acidic amino acid residues and account for nearly 90% of the total in vitro eIF5 phosphorylation. A minor phosphorylation site at Ser-174 was also observed. \| The results suggest that phosphorylation of eIF5 may have a role in stimulating the rate of eIF5-promoted GTP hydrolysis.	SIGNOR-251070
Q07666	Q92793	1	binding	down-regulates activity	0.379	These results suggest that Sam68 and CBP interact in vivo in a manner dependent on the FXE/DXXXL motif. Sam68 Represses CBP-dependent Transcriptional Activation	SIGNOR-266202
Q9Y385	Q92813	1	ubiquitination	down-regulates quantity by destabilization	0.379	ER residency places D2 physically close to an array of proteins that interact and modify the D2 molecule via ubiquitination and targeting to the proteasomal system, explaining its relatively short half-life. Both ubiquitin conjugases UBC6 and or UBC7 interact with D2 and support D2 ubiquitination. Two Lys residues in D2 are involved in this process, K237 and K244.	SIGNOR-267481
Q16566	P14866	1	phosphorylation	up-regulates	0.379	Here we show that the regulation of the stress axis-regulated exon of the slo1 potassium channel transcripts by membrane depolarization requires a highly conserved camkiv target serine (ser-513) of the heterogeneous ribonucleoprotein l. Ser-513 phosphorylation within the rna recognition motif 4 enhanced heterogeneous ribonucleoprotein l interaction with the camkiv-responsive rna element 1 of stress axis-regulated exon and inhibited binding of the large subunit of the u2 auxiliary factor u2af65.	SIGNOR-197367
Q9UM73	Q92569	1	phosphorylation	up-regulates activity	0.379	Subsequent studies revealed that ALK promoted cell migration through the P3K-AKT pathway via the p55γ regulatory subunit of PI3K.	SIGNOR-253217
O43164	P10644	1	polyubiquitination	down-regulates quantity by destabilization	0.379	Praja2 controls the stability of PKA regulatory subunits. Praja2 ubiquitylates RIIα/β subunits. Subunits	SIGNOR-271855
Q96EB6	P17861-2	1	deacetylation	down-regulates activity	0.379	P300 increases the acetylation and protein stability of XBP1s, and enhances its transcriptional activity, whereas SIRT1 deacetylates XBP1s and inhibits its transcriptional activity.. The mRNA encoding the active spliced form of XBP1 (XBP1s) is generated from the unspliced form by IRE1 (inositol-requiring enzyme 1) during the UPR.	SIGNOR-260430
P12931	Q96RD7	1	phosphorylation	up-regulates activity	0.379	We recently identified amino acids 198-200 (YLK) on the PANX1 intracellular loop that are critical for α1-AR-mediated vasoconstriction and PANX1 channel function. We report herein that the YLK motif is contained within an SRC homology 2 domain and is directly phosphorylated by SRC proto-oncogene, nonreceptor tyrosine kinase (SRC) at Tyr198	SIGNOR-277817
P49841	P49715	1	phosphorylation	up-regulates activity	0.379	Glycogen synthase kinase 3 (GSK3) phosphorylates T222 and T226, causing a conformational change in C/EBPα. GSK3-mediated phosphorylation does not, in itself, dramatically alter the activity of C/EBPα in our assays. phosphorylation of C/EBPalpha and other substrates by GSK3 may be required for adipogenesis, since treatment of differentiating preadipocytes with lithium inhibits their conversion to adipocytes.	SIGNOR-251231
O15111	P24385	1	phosphorylation	down-regulates	0.379	Ikkalpha regulates subcellular localization and proteolysis of cyclin d1 by phosphorylation of cyclin d1 at thr286.	SIGNOR-139570
Q16539	P41970	1	phosphorylation	up-regulates	0.379	Tcf sap-1a is efficiently phosphorylated by p38 map kinase in vitro and in vivo on the homologous residues ser381 and ser387. Mutation of these sites to alanine severely reduces c-fos sre-dependent transcription mediated by sap-1a and p38 map kinase.	SIGNOR-47685
P43699	P07202	1	transcriptional regulation	up-regulates quantity by expression	0.379	TSH regulates TPO expression through the cAMP pathway and acts with thyroid-specific transcription factors such as TTF-1, TTF-2 and Pax-8.	SIGNOR-267278
Q8N5S9	P31749	1	phosphorylation	up-regulates activity	0.379	Protein kinase B (PKB) was recently reported to be activated on the phosphorylation of Thr(308) by Ca(2+)/calmodulin-dependent protein kinase kinase alpha (CaM-kinase kinase alpha), suggesting that PKB was regulated through not only the phosphoinositide 3-kinase pathway but also the Ca(2+)/calmodulin protein kinase pathway.	SIGNOR-252609
P60510	O15379	1	dephosphorylation	down-regulates activity	0.379	Here we demonstrate that, in addition to protein-protein interactions with NCoR/SMRT, the activity of HDAC3 is regulated by both phosphorylation and dephosphorylation. A protein kinase CK2 phosphoacceptor site in the HDAC3 protein was identified at position Ser424, which is a nonconserved residue among the class I HDACs. Mutation of this residue was found to reduce deacetylase activity.\|Significantly, both overexpression and siRNA knock-down approaches, and analysis of cells devoid of PP4c, unequivocally show that HDAC3 activity is inversely proportional to the cellular abundance of PP4(c).	SIGNOR-248548
P19544	Q9Y6K1	1	transcriptional regulation	up-regulates quantity by expression	0.379	Here, we show that Wilms' tumour 1 (WT1), a developmental master regulator that can also act as a tumour suppressor or oncoprotein, transcriptionally regulates the de novo DNA methyltransferase 3A (DNMT3A) and that cellular WT1 levels can influence DNA methylation of gene promoters genome-wide. we demonstrate that depletion of WT1 by short-interfering RNAs leads to reduced DNMT3A in Wilms' tumour cells and human embryonal kidney-derived cell lines. Chromatin immunoprecipitation assays demonstrate WT1 recruitment to the DNMT3A promoter region and reporter assays confirm that WT1 directly transactivates DNMT3A expression.	SIGNOR-255904
Q9UNE7	Q86WG3	1	polyubiquitination	down-regulates quantity by destabilization	0.378	CHIP e.g. was found to efficiently polyubiquitinate caytaxin in vitro, suggesting that it might influence caytaxin degradation in vivo.	SIGNOR-272651
P23471	P35222	1	dephosphorylation	up-regulates activity	0.378	PTPRZ1 constitutively promotes the tyrosine dephosphorylation of \u03b2-catenin, and thus \u03b2-catenin participation in TCF-mediated transcription.	SIGNOR-277044
Q05209	P06213	1	dephosphorylation	down-regulates	0.378	Interestingly, all PTPs that were tested could completely dephosphorylate the receptor, given sufficient time, including a negative control (PTP-PEST) that failed to bind IRK as a trapping mutant.	SIGNOR-75894
P03956	P02452	1	cleavage	down-regulates quantity by destabilization	0.378	In vitro, MMP1 initiates degradation of native fibrillar collagens, crucial components of vertebrate extracellular matrix (ECM), by cleaving the peptide bond between Gly775–Ile776 or Gly775–Lys776 in native type I, II or III collagen molecules3,4.	SIGNOR-272336
P68400	P30260	1	phosphorylation	up-regulates	0.378	We report here that phosphorylation of cdc27, a core subunit of apc, in response to tgf- signaling can facilitate the activation of apc.we have demonstrated that casein kinase ii (ckii) is involved in the phosphorylation of cdc27 in response to tgf- signaling.	SIGNOR-170872
P12931	Q96KG7	1	phosphorylation	up-regulates activity	0.378	Our data suggest that c-Src augments the phosphorylation of MEGF10 and helps form a signaling complex.\|These results indicate that overexpressed MEGF10 is phosphorylated by c-Src.	SIGNOR-279290
P27707	P06493	1	binding	down-regulates activity	0.378	We demonstrate that dCK interacts with cyclin-dependent kinase 1 (Cdk1) after IR and that the interaction inhibits Cdk1 activity both in vitro and in vivo.	SIGNOR-275805
Q13315	Q13362-1	1	phosphorylation	up-regulates activity	0.378	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-276318
Q9Y5K5	Q15796	1	deubiquitination	up-regulates	0.378	Here, we report a novel interaction between smads and ubiquitin c-terminal hydrolase uch37, a deubiquitinating enzyme that could potentially reverse smurf-mediated ubiquitination. In gst pull down experiments, uch37 bound weakly to smad2 and smad3, and bound very strongly to smad7 in a region that is distinct from the -py- motif in smad7 that interacts with smurf ubiquitin ligases	SIGNOR-138876
P28566	P09471	1	binding	up-regulates activity	0.378	Here we systematically quantified ligand-induced interactions between 148 GPCRs and all 11 unique G alpha subunit C-termini. For each receptor, we probed chimeric G alpha subunit activation via a transforming growth factor-alpha (TGF alpha) shedding response in HEK293 cells lacking endogenous Gq/11- and G12/13- signaling. \| We defined positive coupling if any member of the subfamily scored LogRAi ≥ -1 and negative coupling if all of the members scored LogRAi < -1 (Figure 3A-B). ROC analysis gives AUC = 0.78 (Figure S4A) when considering high-confidence known coupling data and suggested a threshold of LogRAi ≥ -1.0 for defining true couplings. \| The score associated to this interaction has a LogRAi ≥ -1.0.	SIGNOR-256984
P43405	Q8IWV1	1	phosphorylation	up-regulates activity	0.378	Upon stimulation via the B or T cell receptors, LAX is rapidly phosphorylated by Src and Syk family tyrosine kinases and interacts with Grb2, Gads, and p85.	SIGNOR-273535
Q15831	P49841	1	phosphorylation	down-regulates activity	0.378	In this regard, it was shown that LKB1 physically associates with PKC-zeta, which is known to inhibit GSK3beta kinase activity by promoting its phosphorylation.\|Thus, inhibitory phosphorylation of GSK3beta by LKB1 and/or AKT may be a cardinal event leading to constitutive activation of Wnt and beta-catenin signaling (XREF_FIG).	SIGNOR-280148
Q9Y4K3	O95551	2	ubiquitination	up-regulates activity	0.378	TTRAP is ubiquitylated by TRAF6 and promotes TRAF6 dependent ubiquitylation of TAK1.\|In addition, we noted that the presence of TRAF6 strengthened the interaction between TTRAP and the TGF-\u03b2 receptor complex (see also later).	SIGNOR-278717
O75553	P46531	1	binding	up-regulates	0.378	The induction of disabled-1 (dab-1) tyrosine phosphorylation, and the subsequent activation of src family kinases, were found to be essential steps for the activation of notch-1 signaling by reelin	SIGNOR-196438
P19784	Q9NQB0	1	phosphorylation	up-regulates activity	0.378	We show here that Tcf-4 can be phosphorylated in vitro by protein kinase CK2 stoichiometrically in amino acids Ser-58-Ser-59-Ser-60. Phosphorylation of these residues does not modify the interaction of Tcf-4 with beta-catenin but reduces its association to plakoglobin. \| Experiments performed using a Tcf-4 mutant with decreased interaction to plakoglobin demonstrated that binding to this protein negatively affected the transcriptional activity of Tcf-4.	SIGNOR-251044
P62140	P35240	1	dephosphorylation	up-regulates	0.378	When serine 518 is dephosphorylated by the myosin phosphatase mypt-1-pp1?, The tumor suppressor function of merlin is activated, inhibiting the ras signaling pathway and leading to growth arrest	SIGNOR-159836
O75925	P31749	1	sumoylation	up-regulates activity	0.378	Although multiple sites on Akt could be SUMOylated, K276 was identified as a major SUMO acceptor site. K276R or E278A mutation reduced SUMOylation of Akt but had little effect on its ubiquitination. Strikingly, these mutations also completely abolished Akt kinase activity. In support of these results, we found that expression of PIAS1 and SUMO1 increased Akt activity, whereas expression of SENP1 reduced Akt1 activity.	SIGNOR-252735
O14920	Q9Y6Q9	1	phosphorylation	up-regulates activity	0.378	We demonstrated the in vitro phosphorylation of SRC-3 by the two catalytic subunits of the IKK complex, IKKα and IKKβ. IKK kinase activity is required for synergistic activation with SRC-3	SIGNOR-251298
P07948	P42768	1	phosphorylation	up-regulates activity	0.378	We demonstrated that WASP is phosphorylated on tyrosine 291 in macrophages, and the WASP phosphorylation is important for the phagocytic cup formation. In addition, we showed that WASP and WASP-interacting protein (WIP) form a complex at the phagocytic cup and that the WASP.WIP complex plays a critical role in the phagocytic cup formation.	SIGNOR-273959
Q13309	P10244	1	polyubiquitination	down-regulates quantity by destabilization	0.378	P19Skp1 and Cul-1 bind to the F-box protein p45Skp2 to form a complex (SCF) that functions as E3 ubiquitin ligase.We show that B-Myb physically and functionally interacts with components of the Cdc34-SCFp45Skp2 ubiquitin pathway and propose that B-Myb degradation may be required for controlling the correct alternation of events during progression through the cell division cycle.	SIGNOR-272572
O95551	Q9Y4K3	2	binding	up-regulates activity	0.378	TTRAP associates with TRAF6.The TAK1-TTRAP-TRAF6 complex is stabilized by ubiquitylation and recruited to TβRI.	SIGNOR-277189
Q13153	P63167	1	phosphorylation	down-regulates	0.378	Dlc1 phosphorylation on ser(88) by p21-activated kinase 1 (pak1), a signaling nodule, promotes mammalian cell survival by regulating its interaction with bim and the stability of bim. Here we discovered that phosphorylation of ser(88), which juxtapose each other at the interface of the dlc dimer, disrupts dlc1 dimer formation and consequently impairs its interaction with bim	SIGNOR-159995
P49915	P04637	2	binding	up-regulates	0.378	In response to genotoxic stress or nucleotide deprivation, gmps becomes nuclear and facilitates p53 stabilization by promoting its transfer from mdm2 to a gmps-usp7 deubiquitylation complex.	SIGNOR-204409
P04637	P49915	2	transcriptional regulation	down-regulates quantity by repression	0.378	Herein, we identified GMP synthetase (GMPS), a key enzyme of de novo purine biosynthesis, as an important p53 repression target using a large-scale proteomics approach. This p53-mediated repression of GMPS could be validated by immunoblotting in Sk-Hep1, HepG2, and HuH6 cells.	SIGNOR-267342
Q13315	Q13362-3	1	phosphorylation	up-regulates activity	0.378	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-276320
P18031	P04629	1	dephosphorylation	down-regulates activity	0.378	PTP1B inactivation prevents TrkA exit from soma and causes receptor degradation, suggesting a " gate-keeper " mechanism that ensures targeting of inactive receptors to axons to engage with ligand.\|We identify a gate keeping mechanism in which TrkA receptors, destined for transcytosis, are dephosphorylated in neuronal soma by the ER-resident tyrosine phosphatase, PTP1B.	SIGNOR-277081
Q5JUK2	P21754	1	transcriptional regulation	up-regulates quantity by expression	0.378	Cotransfection of a mouse Sohlh1 expression vector with E box-containing promoter regions of mouse Lhx8, Zp1, and Zp3 fused to luciferase resulted in significant transactivation . Mutation of the E box sequences abolished SOHLH1-dependent stimulation. Thus, Lhx8, Zp1, and Zp3 are likely direct downstream target genes of SOHLH1 through the E box elements in their promoters.	SIGNOR-266078
P49841	P30405	1	phosphorylation	up-regulates activity	0.378	Phosphorylation of cyclophilin D at serine 191 regulates mitochondrial permeability transition pore opening and cell death after ischemia-reperfusion\|We conclude that CypD phosphorylation at S191 residue leads to its binding to OSCP and thus sensitizes mPTP opening for the subsequent cell death.\|Under baseline condition (WT group), the phosphorylation of CypD by a kinase (e.g. GSK3beta) at S191 induces its translocation to the OSCP, to favor mPTP opening and subsequent cell death at reperfusion.	SIGNOR-264880
Q16512	Q16539	1	phosphorylation	up-regulates	0.378	At the same time, rho signals to c-jun n-terminal kinase (jnk) and p38 through rock and protein kinase n (pkn), leading to the transcriptional regulation of jun	SIGNOR-152765
P35452	Q9Y5Q3	1	binding	down-regulates activity	0.378	Hoxd12 and MHox, that interact with v-/c-Maf, using the phage display method. The Hox proteins also could associate with the other Maf protein family members, MafB, MafK, MafF, and MafG, but not with Jun and Fos. The Hox proteins negatively regulated the DNA binding, transactivation and cell-transforming abilities of Maf.	SIGNOR-221896
Q9UNE7	P56817	1	ubiquitination	down-regulates quantity	0.378	This result establishes that CHIP negatively regulates BACE1 stability.\|Thus, both deletion mutants of CHIP could not enhance the ubiquitination of BACE1, suggesting that both domains of CHIP were essential for ubiquitination and degradation of BACE1.	SIGNOR-278719
P50613	P10275	1	phosphorylation	down-regulates	0.377	Here, we show that the transcription factor tfiih, via its cdk7 kinase, phosphorylates the androgen receptor (ar) at position ar/s515. Strikingly, this phosphorylation is a key step for an accurate transactivation that includes the cyclic recruitment of the transcription machinery, the mdm2 e3 ligase, the subsequent ubiquitination of ar at the promoter of target genes and its degradation by the proteasome machinery	SIGNOR-170599
P67775	Q05655	1	dephosphorylation	down-regulates activity	0.377	PP2A(c) displayed the highest specific activity towards PKCdelta. The role of PP2A(c) in the dephosphorylation of PKCdelta in cells was supported by the demonstration that these proteins could be co-immunoprecipitated from NIH3T3 cells.\|In conclusion, the evidence here indicates that PKCdelta de-phosphorylation and hence inactivation is effected by PP2A with which it forms a complex	SIGNOR-248638
Q16620	P22001	1	phosphorylation	down-regulates	0.377	Previously we have shown that acute brain-derived neurotrophic factor (bdnf) activation of neurotrophin receptor tyrosine kinase b (trkb) suppresses the shaker voltage-gated potassium channel (kv1.3) via phosphorylation of multiple tyrosine residues in the n and c terminal aspects of the channel protein.	SIGNOR-183515
Q05209	O60674	1	dephosphorylation	down-regulates activity	0.377	PTP-PEST-Containing Lysates from EGF-Treated HC11 Cells Dephosphorylate JAK2 More Efficiently than Lysates from Control Cells\|phospho-JAK2-specific rabbit polyclonal antiserum (44-426, BioSource Technologies, Inc., Camarillo, CA) which recognizes Tyr1007/1008 in the activation site	SIGNOR-248657
P32248	P32121	1	relocalization	up-regulates activity	0.377	B-Arrestin-2 is recruited to CCR7 following stimulation with CCL19, but not CCL21.	SIGNOR-278124
P42574	P08590	1	cleavage	down-regulates quantity by destabilization	0.377	By sequencing and site-directed mutagenesis, a noncanonical cleavage site for caspase-3 was mapped to the C-terminal DFVE(135)G motif. We demonstrated that vMLC1 cleavage in failing myocardium in vivo is associated with a morphological disruption of the organized vMLC1 staining of sarcomeres, and with a reduction in myocyte contractile performance.	SIGNOR-270593
P06213	P07550	1	phosphorylation	down-regulates activity	0.377	Insulin (10 nM)-stimulated rIR-catalyzed phosphorylation of β2-adrenergic receptor peptides was found prominently in peptides L339 (Tyr350 and Tyr354), T362 (Tyr364), and to a lesser extent peptides Y132 (Tyr132 and Tyr141), and I135 (Tyr141). G-protein-linked receptors and intrinsic tyrosine-kinase growth receptors represent two prominent modalities in cell signaling. Cross-regulation among members of both receptor superfamilies has been reported, including the counter-regulatory effects of insulin on β-adrenergic catecholamine action. Cells stimulated by insulin show loss of function and increased phosphotyrosine content of β2-adrenergic receptors.	SIGNOR-251302
Q8WZ19	P61586	1	binding	down-regulates quantity	0.377	BACURDs form ubiquitin ligase complexes, which selectively ubiquitinate RhoA, with Cul3. Our studies reveal a previously unknown mechanism for controlling RhoA degradation and regulating RhoA function in various biological contexts, which involves a Cul3/BACURD ubiquitin ligase complex.	SIGNOR-264236
Q13164	P37231	1	binding	up-regulates activity	0.377	In endothelial cells, flow-mediated activation of ERK5 has been shown to lead to activation of PPAR gamma by direct binding to the hinge-helix region of PPAR gamma	SIGNOR-278108
P12931	P84022	1	phosphorylation	up-regulates activity	0.377	Although the role of ERK in mediating phosphorylation of Smad2/3 remains to be investigated, our data indicate that early Smad3 phosphorylation is independent of transient EGFR transactivation and ERK1/2 activation initiated by HB-EGF release, whereas Src mediated chronic EGFR transactivation and ERK1/2 activation involve late Smad3 activation induced by TGF-beta1.\|Inhibition of Src not only decreases Smad3 phosphorylation but also decreases phosphorylation dependent nuclear translocation of Smad2/3, suggesting that Src kinase could modulate Smad3 activity.	SIGNOR-279292
Q16659	O95551	1	phosphorylation	up-regulates activity	0.377	ERK3 phosphorylates TDP2 and promotes its phosphodiesterase activity, thereby upregualting TDP2-mediated DNA damage response and desensitizing lung cancer cells to Top2 inhibitor-induced growth inhibition.\|In the current study, we have found that ERK3, an atypical MAPK, phosphorylates TDP2 at S60 and regulates TDP2 's phosphodiesterase activity, thereby cooperatively protecting lung cancer cells against Top2 inhibitors induced DNA damage and growth inhibition.	SIGNOR-278245
O15297	P13051	1	dephosphorylation	down-regulates activity	0.377	PPM1D dephosphorylation of UNG2 is correlated with reduced UNG2 activity on uracil-containing templates.\|This result suggests that PPM1D specifically inhibits UNG2 and not other uracil DNA glycosylases.	SIGNOR-277156
Q8WZA2	P01308	1	relocalization	up-regulates quantity	0.377	Activation of EPAC2 has recently been shown to increase the density of insulin‐containing granules near the plasma membrane, facilitating insulin secretion from the β cells	SIGNOR-278140
P16298	P19484	1	dephosphorylation	up-regulates activity	0.377	Lysosomal Ca2+ release via mucolipin 1 (MCOLN1) activates calcineurin, which binds and de-phosphorylates TFEB, thus promoting its nuclear translocation.	SIGNOR-255306
Q9NU22	Q8IZL8	1	binding	up-regulates quantity by stabilization	0.377	MDN1 Is Physically and Functionally Associated with the Mammalian PELP1 Complex. To more specifically determine a function of mammalian MDN1 in the subnuclear distribution of PELP1-containing pre-60S-particles, we examined PELP1 localization in control cells or cells depleted from MDN1. Importantly, in the absence of MDN1, PELP1 became sequestered in enlarged nucleoli, indicating that MDN1 is involved in the nucleolar release of PELP1-containing pre-60S ribosomes	SIGNOR-261357
Q66K64	Q14498	1	polyubiquitination	down-regulates quantity by destabilization	0.377	Indisulam promotes an interaction between RBM39 and the DCAF15 E3 ligase substrate receptor, leading to RBM39 ubiquitination and proteasome-mediated degradation.	SIGNOR-272203
P62136	P38398	1	dephosphorylation	down-regulates activity	0.377	Protein kinases involved in the DNA damage checkpoint control, such as ATM, ATR, and hCds1/Chk2, have been shown to phosphorylate and activate BRCA1 upon DNA damage. \|Altogether, these results indicate that PP1α specifically dephosphorylates BRCA1 at multiple serine sites, including S988 [12], S1423, and S1524.	SIGNOR-248560
Q13535	Q01094	1	phosphorylation	up-regulates quantity by stabilization	0.377	These results thus suggest that this serine 31 residue is indeed an atm/atr phosphorylation site and in fact is the major site for atm/atr-mediated phosphorylation within e2f1. Thus, it is possible that the atm/atr-mediated phosphorylation inhibits the binding and function of skp2 and thus prevents the normal degradation of e2f1	SIGNOR-109420
Q13237	P48764	1	phosphorylation	down-regulates activity	0.377	CGMP and cGKII increased NHE3 phosphorylation at three sites (rabbit Ser (554), Ser (607), and Ser (663), equivalent to mouse Ser (552), Ser (605), and Ser (659)), all of which had to be present at the same time for cGMP to inhibit NHE3.\|cGMP and cGKII rapidly inhibited NHE3, which was associated with reduced surface NHE3.	SIGNOR-280096
P35452	O60675	1	binding	down-regulates activity	0.377	Hoxd12 and MHox, that interact with v-/c-Maf, using the phage display method. The Hox proteins also could associate with the other Maf protein family members, MafB, MafK, MafF, and MafG, but not with Jun and Fos. The Hox proteins negatively regulated the DNA binding, transactivation and cell-transforming abilities of Maf.	SIGNOR-221929
Q00535	P49023	1	phosphorylation	up-regulates activity	0.377	Thus, phosphorylation of paxillin is involved in NGF-induced neurite extension of PC-12 cells, probably through regulating focal adhesion organization.\|cdk5 and p38MAPK phosphorylates Ser 85 on paxillin in vitro.	SIGNOR-278921
P60953	P49841	1	binding	down-regulates	0.377	Phospho-gsk3b-specific antibodies also revolved that lkb1 regulates gsk3b phosphorylation at a known inhibitory site, serine-9. This localized phosphorylation is cdc42 and pkc-zeta-dependent.	SIGNOR-119885
Q6W2J9	Q13547	1	binding	up-regulates activity	0.377	BCoR can interact w Because HDACs appear to be involved in repression by an increasing number of transcriptional repressors, we tested whether BCoR can associate with HDACs. BCoR can interact with HDAC1, HDAC3, and HDAC-B/5 more strongly than with HDAC-A/4, HDAC-C, HDAC-D, and HDAC-E.	SIGNOR-252236
Q15915	P08151	1	relocalization	up-regulates	0.377	Co-expression of zic1 resulted in gli1 and gli3 proteins being translocated to the nucleus in varying levels	SIGNOR-105491
Q9UM73	P31939	1	phosphorylation	up-regulates activity	0.377	ATIC and VASP phosphorylation is dependent on NPM-ALK kinase activity. ATIC activity is enhanced in the presence of NPM-ALK in vitro.The ATIC activity is enhanced by NPM-ALK in HEK-293T-Rex cells.	SIGNOR-276171
Q00535	P27695	1	phosphorylation	up-regulates activity	0.377	Apurinic/apyrimidinic endonuclease-1 (APE1) is a multifunctional DNA repair/gene regulatory protein in mammalian cells, and was recently reported to be phosphorylated at Thr233 by CDK5.	SIGNOR-276337
O15033	Q9NR28	1	ubiquitination	down-regulates quantity by destabilization	0.377	AREL1 ubiquitinated SMAC, primarily on Lys62 and Lys191 \|E701A substitution in the AREL1 HECT domain substantially increased its autopolyubiquitination and SMAC ubiquitination activity, whereas deletion of the last three amino acids at the C terminus completely abrogated AREL1 autoubiquitination and reduced SMAC ubiquitination.	SIGNOR-267672
O95243	O15528	1	transcriptional regulation	up-regulates quantity by expression	0.377	Phosphorylation of MBD4 promotes 5-meC glycosylase activity Further evidence emerged to support the involvement of MBD4 in active demethylation. Protein-kinase C phosphorylation of MBD4 at two specific serine residues (165 and 262) following parathyroid hormone stimulation was shown to promote demethylation within the CYP27B1 gene promoter [12]	SIGNOR-275682
P24941	P62136	1	phosphorylation	down-regulates activity	0.377	Both of these pp1 isoforms contain an arg-pro-ile/val-thr-pro-pro-arg sequence near the c terminus, a known site of phosphorylation by cdc/cdk kinases, and phosphorylation attenuates phosphatase activity	SIGNOR-92265
Q96J02	Q9HBA0	1	ubiquitination	down-regulates activity	0.377	AIP4 ubiquitin ligase is involved in the ubiquitination of both TRPV4 and TRPC4.Ubiquitination of TRPV4 is dramatically increased by the HECT (homologous to E6-AP carboxyl terminus)-family ubiquitin ligase AIP4 without inducing degradation of this channel. Instead, AIP4 promotes the endocytosis of TRPV4 and decreases its amount at the plasma membrane.	SIGNOR-272625
Q99527	P63092	1	binding	up-regulates activity	0.377	GPCRs transduce their signal via G-protein heterotrimers (αβγ) that dissociate in free Gα-subunit protein and Gβγ-subunit protein complexes following ligand stimulation; the activated receptor induces a conformational change in the associated G protein α-subunit leading to release of GDP followed by binding of GTP and α-subunit dissociation from the receptor.	SIGNOR-251102
Q13131	Q09472	1	phosphorylation	down-regulates	0.376	The mechanism of ampk-mediated anti- inflammation involves the induction of p300 ser89 phosphor- ylation and subsequent inactivation of p300 hat activity.	SIGNOR-176637
O96017	P00441	1	phosphorylation	up-regulates activity	0.376	ROS signaling is mediated by Mec1/ATM and its effector Dun1/Cds1 kinase, through Dun1 interaction with Sod1 and regulation of Sod1 by phosphorylation at S60, 99. In the nucleus, Sod1 binds to the promoters and regulates the expression of oxidative resistance and repair genes.	SIGNOR-262794
P45984	P30307	1	phosphorylation	down-regulates	0.376	Here we show that jnk directly phosphorylates cdc25c at serine 168 during g(2) phase of the cell cycle. Cdc25c phosphorylation by jnk negatively regulates its phosphatase activity and thereby cdk1 activation, enabling a timely control of mitosis onset.	SIGNOR-164093
Q9Y297	Q15910	1	ubiquitination	down-regulates	0.376	_-trcp ubiquitinates ezh2 and jak2-mediated phosphorylation on y641 directs _-trcp-mediated ezh2 degradation.	SIGNOR-204481
Q9UNE7	Q16665	1	ubiquitination	down-regulates quantity by destabilization	0.376	the ubiquitin ligase activity of CHIP regulates HIF-1α degradation.	SIGNOR-271426
P53350	Q9UBW7	1	phosphorylation	down-regulates quantity by destabilization	0.376	PLK1 and HOTAIR Accelerate Proteasomal Degradation of SUZ12 and ZNF198 during Hepatitis B Virus-Induced Liver Carcinogenesis\|Similar analyses with ZNF198 identified two clusters of putative Plk1 phosphorylation sites in vitro. A cluster of serine residues at the N-terminus of ZNF198, S303, S305, and S309, and a cluster at the C-terminus, S1056 and S1064. The triple Ser to Ala mutant, S303A/S305A/S309A, consistently exhibited the lowest level of phosphorylation in vitro, in comparison to the double S1056A/S1064A mutant	SIGNOR-275560
P50750	Q09472	1	phosphorylation	up-regulates activity	0.376	As Cdk9 phosphorylates both RNA polymerase II and p300 and increases p300-HAT activity , the effects of CUR and PyrC on the kinase activity of Cdk9 were examined .\|As Cdk9 phosphorylates both RNA polymerase II and p300 and increases p300-HAT activity, the effects of CUR and PyrC on the kinase activity of Cdk9 were examined.	SIGNOR-279690
O14965	O43521	1	phosphorylation	down-regulates quantity by destabilization	0.376	We observed that BimEL is phosphorylated by Aurora A early in mitosis and reversed by PP2A after mitotic exit. Aurora A phosphorylation stimulated binding of BimEL to the F-box protein beta-transducin repeat containing E3 ubiquitin protein ligase and promoted ubiquitination and degradation of BimEL.	SIGNOR-276248
P35452	O15525	1	binding	down-regulates activity	0.376	Hoxd12 and MHox, that interact with v-/c-Maf, using the phage display method. The Hox proteins also could associate with the other Maf protein family members, MafB, MafK, MafF, and MafG, but not with Jun and Fos. The Hox proteins negatively regulated the DNA binding, transactivation and cell-transforming abilities of Maf.	SIGNOR-221958
Q8IXJ6	P15172	1	deacetylation	down-regulates	0.376	Sir2-mediated deacetylation of myod can be expected to inhibit its transcriptional capabilities.	SIGNOR-104251
Q13464	P35611	1	phosphorylation	up-regulates	0.376	Rho-associated kinase (rho- kinase), which is activated by the small guanosine triphosphatase rho, phosphorylates alpha-adducin and thereby enhances the f-actin-binding activity of alpha-adducin in vitro. Here we identified the sites of phosphorylation of alpha-adducin by rho-kinase as thr445 and thr480	SIGNOR-66996
Q00535	P16949	1	phosphorylation	down-regulates	0.376	Involved in the regulation of the microtubule (mt) filament system by destabilizing microtubules. Prevents assembly and promotes disassembly of microtubules. The kinases involved in phosphorylating stmn ser-16 and ser-63 include camp-dependent protein kinase (pka) and pak1, whereas stmn ser-25 and ser-38 have been shown to be targets for proline-directed serine/threonine kinases such as cyclin-dependent kinases, erk1/2, and members of the p38 mapk subfamily.	SIGNOR-166682
P45984	P49768	1	phosphorylation	up-regulates	0.376	This jnk phosphorylation of ps1 at ser(319)thr(320) enhances the stability of the ps1 c-terminal fragment that is necessary for gamma-secretase activity.	SIGNOR-179676

Q13950

P46531

1

binding

down-regulates

0.38

Runx2 is an inhibitor of the notch1 signaling pathway during normal osteoblast differentiation. The n-terminal domain of runx2 was crucial to the binding and inhibition of the the n-terminus of the notch1 intracellular domain.

SIGNOR-167627

Q9Y3L3

P63000

1

gtpase-activating protein

down-regulates activity

0.38

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-260514

Q9H2X6

Q9P1Z0

1

phosphorylation

down-regulates activity

0.379

The human protein kinase HIPK2 phosphorylates and downregulates the methyl-binding transcription factor ZBTB4.

SIGNOR-262882

P68400

P52655

1

phosphorylation

up-regulates activity

0.379

We now show that human TFIIA is phosphorylated in vivo on serine residues that are partially conserved between yeast and human TFIIA large subunits. Alanine substitution mutation of serine residues 316 and 321 in TFIIA alphabeta reduced TFIIA phosphorylation significantly in vivo. Additional alanine substitutions at serines 280 and 281 reduced phosphorylation to undetectable levels. Mutation of all four serine residues reduced the ability of TFIIA to stimulate transcription in transient transfection assays with various activators and promoters, indicating that TFIIA phosphorylation is required globally for optimal function.

SIGNOR-250877

P14778

P45983

1

phosphorylation

up-regulates activity

0.379

Il-1 binding to its receptor triggers a cascade of signaling events, including activation of the stress-activated mitogen-activated protein (map) kinases, c-jun nh2-terminal kinase (jnk) and p38 map kinase, as well as transcription factor nuclear factor kappab (nf-kappab

SIGNOR-249513

O75056

P46531

1

binding

up-regulates activity

0.379

Furthermore, we show that Syndecan-3 interacts with Notch and is required for Notch processing by ADAM17/tumor necrosis factor-converting enzyme (TACE) and signal transduction. Together, our data support the conclusion that Syndecan-3 and Notch cooperate in regulating homeostasis of the satellite cell population and myofiber size.

SIGNOR-244072

P00519

Q92918

1

phosphorylation

up-regulates activity

0.379

C-Abl phosphorylates HPK1 in cytoplasm and stimulates HPK1 activity. the c-Abl phosphorylation site (YXXP) in HPK1 (Y232QPP; aa 232–235) is localized in HPK1-KD

SIGNOR-251429

Q9UIJ5

P78352

1

palmitoylation

up-regulates activity

0.379

Plasma membrane targeting of DHHC2 palmitoyltransferase rapidly recruited PSD-95 to the plasma membrane and proved essential for postsynaptic nanodomain formation.

SIGNOR-261290

P53350

O60563

1

phosphorylation

down-regulates activity

0.379

Further analysis indicated that Plk1 could phosphorylate cyclin T1 at Ser564 and inhibit the kinase activity of cyclin T1/Cdk9 complex on phosphorylation of the C-terminal domain (CTD) of RNA polymerase II.

SIGNOR-276501

Q5S007

P31749

1

phosphorylation

up-regulates

0.379

Expression of wild-type LRRK2 promoted neuronal survival against apoptosis through activation of the downstream effector, Akt by phosphorylation of Ser473. Phosphorylated Akt in turn inhibited FOXO 1 signaling

SIGNOR-252598

P67870

P55010

1

phosphorylation

up-regulates activity

0.379

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

SIGNOR-251070

Q07666

Q92793

1

binding

down-regulates activity

0.379

These results suggest that Sam68 and CBP interact in vivo in a manner dependent on the FXE/DXXXL motif. Sam68 Represses CBP-dependent Transcriptional Activation

SIGNOR-266202

Q9Y385

Q92813

1

ubiquitination

down-regulates quantity by destabilization

0.379

ER residency places D2 physically close to an array of proteins that interact and modify the D2 molecule via ubiquitination and targeting to the proteasomal system, explaining its relatively short half-life. Both ubiquitin conjugases UBC6 and or UBC7 interact with D2 and support D2 ubiquitination. Two Lys residues in D2 are involved in this process, K237 and K244.

SIGNOR-267481

Q16566

P14866

1

phosphorylation

up-regulates

0.379

Here we show that the regulation of the stress axis-regulated exon of the slo1 potassium channel transcripts by membrane depolarization requires a highly conserved camkiv target serine (ser-513) of the heterogeneous ribonucleoprotein l. Ser-513 phosphorylation within the rna recognition motif 4 enhanced heterogeneous ribonucleoprotein l interaction with the camkiv-responsive rna element 1 of stress axis-regulated exon and inhibited binding of the large subunit of the u2 auxiliary factor u2af65.

SIGNOR-197367

Q9UM73

Q92569

1

phosphorylation

up-regulates activity

0.379

Subsequent studies revealed that ALK promoted cell migration through the P3K-AKT pathway via the p55γ regulatory subunit of PI3K.

SIGNOR-253217

O43164

P10644

1

polyubiquitination

down-regulates quantity by destabilization

0.379

Praja2 controls the stability of PKA regulatory subunits. Praja2 ubiquitylates RIIα/β subunits. Subunits

SIGNOR-271855

Q96EB6

P17861-2

1

deacetylation

down-regulates activity

0.379

P300 increases the acetylation and protein stability of XBP1s, and enhances its transcriptional activity, whereas SIRT1 deacetylates XBP1s and inhibits its transcriptional activity.. The mRNA encoding the active spliced form of XBP1 (XBP1s) is generated from the unspliced form by IRE1 (inositol-requiring enzyme 1) during the UPR.

SIGNOR-260430

P12931

Q96RD7

1

phosphorylation

up-regulates activity

0.379

We recently identified amino acids 198-200 (YLK) on the PANX1 intracellular loop that are critical for α1-AR-mediated vasoconstriction and PANX1 channel function. We report herein that the YLK motif is contained within an SRC homology 2 domain and is directly phosphorylated by SRC proto-oncogene, nonreceptor tyrosine kinase (SRC) at Tyr198

SIGNOR-277817

P49841

P49715

1

phosphorylation

up-regulates activity

0.379

Glycogen synthase kinase 3 (GSK3) phosphorylates T222 and T226, causing a conformational change in C/EBPα. GSK3-mediated phosphorylation does not, in itself, dramatically alter the activity of C/EBPα in our assays. phosphorylation of C/EBPalpha and other substrates by GSK3 may be required for adipogenesis, since treatment of differentiating preadipocytes with lithium inhibits their conversion to adipocytes.

SIGNOR-251231

O15111

P24385

1

phosphorylation

down-regulates

0.379

Ikkalpha regulates subcellular localization and proteolysis of cyclin d1 by phosphorylation of cyclin d1 at thr286.

SIGNOR-139570

Q16539

P41970

1

phosphorylation

up-regulates

0.379

Tcf sap-1a is efficiently phosphorylated by p38 map kinase in vitro and in vivo on the homologous residues ser381 and ser387. Mutation of these sites to alanine severely reduces c-fos sre-dependent transcription mediated by sap-1a and p38 map kinase.

SIGNOR-47685

P43699

P07202

1

transcriptional regulation

up-regulates quantity by expression

0.379

TSH regulates TPO expression through the cAMP pathway and acts with thyroid-specific transcription factors such as TTF-1, TTF-2 and Pax-8.

SIGNOR-267278

Q8N5S9

P31749

1

phosphorylation

up-regulates activity

0.379

Protein kinase B (PKB) was recently reported to be activated on the phosphorylation of Thr(308) by Ca(2+)/calmodulin-dependent protein kinase kinase alpha (CaM-kinase kinase alpha), suggesting that PKB was regulated through not only the phosphoinositide 3-kinase pathway but also the Ca(2+)/calmodulin protein kinase pathway.

SIGNOR-252609

P60510

O15379

1

dephosphorylation

down-regulates activity

0.379

Here we demonstrate that, in addition to protein-protein interactions with NCoR/SMRT, the activity of HDAC3 is regulated by both phosphorylation and dephosphorylation. A protein kinase CK2 phosphoacceptor site in the HDAC3 protein was identified at position Ser424, which is a nonconserved residue among the class I HDACs. Mutation of this residue was found to reduce deacetylase activity.|Significantly, both overexpression and siRNA knock-down approaches, and analysis of cells devoid of PP4c, unequivocally show that HDAC3 activity is inversely proportional to the cellular abundance of PP4(c).

SIGNOR-248548

P19544

Q9Y6K1

1

transcriptional regulation

up-regulates quantity by expression

0.379

Here, we show that Wilms' tumour 1 (WT1), a developmental master regulator that can also act as a tumour suppressor or oncoprotein, transcriptionally regulates the de novo DNA methyltransferase 3A (DNMT3A) and that cellular WT1 levels can influence DNA methylation of gene promoters genome-wide. we demonstrate that depletion of WT1 by short-interfering RNAs leads to reduced DNMT3A in Wilms' tumour cells and human embryonal kidney-derived cell lines. Chromatin immunoprecipitation assays demonstrate WT1 recruitment to the DNMT3A promoter region and reporter assays confirm that WT1 directly transactivates DNMT3A expression.

SIGNOR-255904

Q9UNE7

Q86WG3

1

polyubiquitination

down-regulates quantity by destabilization

0.378

CHIP e.g. was found to efficiently polyubiquitinate caytaxin in vitro, suggesting that it might influence caytaxin degradation in vivo.

SIGNOR-272651

P23471

P35222

1

dephosphorylation

up-regulates activity

0.378

PTPRZ1 constitutively promotes the tyrosine dephosphorylation of \u03b2-catenin, and thus \u03b2-catenin participation in TCF-mediated transcription.

SIGNOR-277044

Q05209

P06213

1

dephosphorylation

down-regulates

0.378

Interestingly, all PTPs that were tested could completely dephosphorylate the receptor, given sufficient time, including a negative control (PTP-PEST) that failed to bind IRK as a trapping mutant.

SIGNOR-75894

P03956

P02452

1

cleavage

down-regulates quantity by destabilization

0.378

In vitro, MMP1 initiates degradation of native fibrillar collagens, crucial components of vertebrate extracellular matrix (ECM), by cleaving the peptide bond between Gly775–Ile776 or Gly775–Lys776 in native type I, II or III collagen molecules3,4.

SIGNOR-272336

P68400

P30260

1

phosphorylation

up-regulates

0.378

We report here that phosphorylation of cdc27, a core subunit of apc, in response to tgf- signaling can facilitate the activation of apc.we have demonstrated that casein kinase ii (ckii) is involved in the phosphorylation of cdc27 in response to tgf- signaling.

SIGNOR-170872

P12931

Q96KG7

1

phosphorylation

up-regulates activity

0.378

Our data suggest that c-Src augments the phosphorylation of MEGF10 and helps form a signaling complex.|These results indicate that overexpressed MEGF10 is phosphorylated by c-Src.

SIGNOR-279290

P27707

P06493

1

binding

down-regulates activity

0.378

We demonstrate that dCK interacts with cyclin-dependent kinase 1 (Cdk1) after IR and that the interaction inhibits Cdk1 activity both in vitro and in vivo.

SIGNOR-275805

Q13315

Q13362-1

1

phosphorylation

up-regulates activity

0.378

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-276318

Q9Y5K5

Q15796

1

deubiquitination

up-regulates

0.378

Here, we report a novel interaction between smads and ubiquitin c-terminal hydrolase uch37, a deubiquitinating enzyme that could potentially reverse smurf-mediated ubiquitination. In gst pull down experiments, uch37 bound weakly to smad2 and smad3, and bound very strongly to smad7 in a region that is distinct from the -py- motif in smad7 that interacts with smurf ubiquitin ligases

SIGNOR-138876

P28566

P09471

1

binding

up-regulates activity

0.378

Here we systematically quantified ligand-induced interactions between 148 GPCRs and all 11 unique G alpha subunit C-termini. For each receptor, we probed chimeric G alpha subunit activation via a transforming growth factor-alpha (TGF alpha) shedding response in HEK293 cells lacking endogenous Gq/11- and G12/13- signaling. | We defined positive coupling if any member of the subfamily scored LogRAi ≥ -1 and negative coupling if all of the members scored LogRAi < -1 (Figure 3A-B). ROC analysis gives AUC = 0.78 (Figure S4A) when considering high-confidence known coupling data and suggested a threshold of LogRAi ≥ -1.0 for defining true couplings. | The score associated to this interaction has a LogRAi ≥ -1.0.

SIGNOR-256984

P43405

Q8IWV1

1

phosphorylation

up-regulates activity

0.378

Upon stimulation via the B or T cell receptors, LAX is rapidly phosphorylated by Src and Syk family tyrosine kinases and interacts with Grb2, Gads, and p85.

SIGNOR-273535

Q15831

P49841

1

phosphorylation

down-regulates activity

0.378

In this regard, it was shown that LKB1 physically associates with PKC-zeta, which is known to inhibit GSK3beta kinase activity by promoting its phosphorylation.|Thus, inhibitory phosphorylation of GSK3beta by LKB1 and/or AKT may be a cardinal event leading to constitutive activation of Wnt and beta-catenin signaling (XREF_FIG).

SIGNOR-280148

Q9Y4K3

O95551

2

ubiquitination

up-regulates activity

0.378

TTRAP is ubiquitylated by TRAF6 and promotes TRAF6 dependent ubiquitylation of TAK1.|In addition, we noted that the presence of TRAF6 strengthened the interaction between TTRAP and the TGF-\u03b2 receptor complex (see also later).

SIGNOR-278717

O75553

P46531

1

binding

up-regulates

0.378

The induction of disabled-1 (dab-1) tyrosine phosphorylation, and the subsequent activation of src family kinases, were found to be essential steps for the activation of notch-1 signaling by reelin

SIGNOR-196438

P19784

Q9NQB0

1

phosphorylation

up-regulates activity

0.378

We show here that Tcf-4 can be phosphorylated in vitro by protein kinase CK2 stoichiometrically in amino acids Ser-58-Ser-59-Ser-60. Phosphorylation of these residues does not modify the interaction of Tcf-4 with beta-catenin but reduces its association to plakoglobin. | Experiments performed using a Tcf-4 mutant with decreased interaction to plakoglobin demonstrated that binding to this protein negatively affected the transcriptional activity of Tcf-4.

SIGNOR-251044

P62140

P35240

1

dephosphorylation

up-regulates

0.378

When serine 518 is dephosphorylated by the myosin phosphatase mypt-1-pp1?, The tumor suppressor function of merlin is activated, inhibiting the ras signaling pathway and leading to growth arrest

SIGNOR-159836

O75925

P31749

1

sumoylation

up-regulates activity

0.378

Although multiple sites on Akt could be SUMOylated, K276 was identified as a major SUMO acceptor site. K276R or E278A mutation reduced SUMOylation of Akt but had little effect on its ubiquitination. Strikingly, these mutations also completely abolished Akt kinase activity. In support of these results, we found that expression of PIAS1 and SUMO1 increased Akt activity, whereas expression of SENP1 reduced Akt1 activity.

SIGNOR-252735

O14920

Q9Y6Q9

1

phosphorylation

up-regulates activity

0.378

We demonstrated the in vitro phosphorylation of SRC-3 by the two catalytic subunits of the IKK complex, IKKα and IKKβ. IKK kinase activity is required for synergistic activation with SRC-3

SIGNOR-251298

P07948

P42768

1

phosphorylation

up-regulates activity

0.378

We demonstrated that WASP is phosphorylated on tyrosine 291 in macrophages, and the WASP phosphorylation is important for the phagocytic cup formation. In addition, we showed that WASP and WASP-interacting protein (WIP) form a complex at the phagocytic cup and that the WASP.WIP complex plays a critical role in the phagocytic cup formation.

SIGNOR-273959

Q13309

P10244

1

polyubiquitination

down-regulates quantity by destabilization

0.378

P19Skp1 and Cul-1 bind to the F-box protein p45Skp2 to form a complex (SCF) that functions as E3 ubiquitin ligase.We show that B-Myb physically and functionally interacts with components of the Cdc34-SCFp45Skp2 ubiquitin pathway and propose that B-Myb degradation may be required for controlling the correct alternation of events during progression through the cell division cycle.

SIGNOR-272572

O95551

Q9Y4K3

2

binding

up-regulates activity

0.378

TTRAP associates with TRAF6.The TAK1-TTRAP-TRAF6 complex is stabilized by ubiquitylation and recruited to TβRI.

SIGNOR-277189

Q13153

P63167

1

phosphorylation

down-regulates

0.378

Dlc1 phosphorylation on ser(88) by p21-activated kinase 1 (pak1), a signaling nodule, promotes mammalian cell survival by regulating its interaction with bim and the stability of bim. Here we discovered that phosphorylation of ser(88), which juxtapose each other at the interface of the dlc dimer, disrupts dlc1 dimer formation and consequently impairs its interaction with bim

SIGNOR-159995

P49915

P04637

2

binding

up-regulates

0.378

In response to genotoxic stress or nucleotide deprivation, gmps becomes nuclear and facilitates p53 stabilization by promoting its transfer from mdm2 to a gmps-usp7 deubiquitylation complex.

SIGNOR-204409

P04637

P49915

2

transcriptional regulation

down-regulates quantity by repression

0.378

Herein, we identified GMP synthetase (GMPS), a key enzyme of de novo purine biosynthesis, as an important p53 repression target using a large-scale proteomics approach. This p53-mediated repression of GMPS could be validated by immunoblotting in Sk-Hep1, HepG2, and HuH6 cells.

SIGNOR-267342

Q13315

Q13362-3

1

phosphorylation

up-regulates activity

0.378

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-276320

P18031

P04629

1

dephosphorylation

down-regulates activity

0.378

PTP1B inactivation prevents TrkA exit from soma and causes receptor degradation, suggesting a " gate-keeper " mechanism that ensures targeting of inactive receptors to axons to engage with ligand.|We identify a gate keeping mechanism in which TrkA receptors, destined for transcytosis, are dephosphorylated in neuronal soma by the ER-resident tyrosine phosphatase, PTP1B.

SIGNOR-277081

Q5JUK2

P21754

1

transcriptional regulation

up-regulates quantity by expression

0.378

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

SIGNOR-266078

P49841

P30405

1

phosphorylation

up-regulates activity

0.378

Phosphorylation of cyclophilin D at serine 191 regulates mitochondrial permeability transition pore opening and cell death after ischemia-reperfusion|We conclude that CypD phosphorylation at S191 residue leads to its binding to OSCP and thus sensitizes mPTP opening for the subsequent cell death.|Under baseline condition (WT group), the phosphorylation of CypD by a kinase (e.g. GSK3beta) at S191 induces its translocation to the OSCP, to favor mPTP opening and subsequent cell death at reperfusion.

SIGNOR-264880

Q16512

Q16539

1

phosphorylation

up-regulates

0.378

At the same time, rho signals to c-jun n-terminal kinase (jnk) and p38 through rock and protein kinase n (pkn), leading to the transcriptional regulation of jun

SIGNOR-152765

P35452

Q9Y5Q3

1

binding

down-regulates activity

0.378

Hoxd12 and MHox, that interact with v-/c-Maf, using the phage display method. The Hox proteins also could associate with the other Maf protein family members, MafB, MafK, MafF, and MafG, but not with Jun and Fos. The Hox proteins negatively regulated the DNA binding, transactivation and cell-transforming abilities of Maf.

SIGNOR-221896

Q9UNE7

P56817

1

ubiquitination

down-regulates quantity

0.378

This result establishes that CHIP negatively regulates BACE1 stability.|Thus, both deletion mutants of CHIP could not enhance the ubiquitination of BACE1, suggesting that both domains of CHIP were essential for ubiquitination and degradation of BACE1.

SIGNOR-278719

P50613

P10275

1

phosphorylation

down-regulates

0.377

Here, we show that the transcription factor tfiih, via its cdk7 kinase, phosphorylates the androgen receptor (ar) at position ar/s515. Strikingly, this phosphorylation is a key step for an accurate transactivation that includes the cyclic recruitment of the transcription machinery, the mdm2 e3 ligase, the subsequent ubiquitination of ar at the promoter of target genes and its degradation by the proteasome machinery

SIGNOR-170599

P67775

Q05655

1

dephosphorylation

down-regulates activity

0.377

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

SIGNOR-248638

Q16620

P22001

1

phosphorylation

down-regulates

0.377

Previously we have shown that acute brain-derived neurotrophic factor (bdnf) activation of neurotrophin receptor tyrosine kinase b (trkb) suppresses the shaker voltage-gated potassium channel (kv1.3) via phosphorylation of multiple tyrosine residues in the n and c terminal aspects of the channel protein.

SIGNOR-183515

Q05209

O60674

1

dephosphorylation

down-regulates activity

0.377

PTP-PEST-Containing Lysates from EGF-Treated HC11 Cells Dephosphorylate JAK2 More Efficiently than Lysates from Control Cells|phospho-JAK2-specific rabbit polyclonal antiserum (44-426, BioSource Technologies, Inc., Camarillo, CA) which recognizes Tyr1007/1008 in the activation site

SIGNOR-248657

P32248

P32121

1

relocalization

up-regulates activity

0.377

B-Arrestin-2 is recruited to CCR7 following stimulation with CCL19, but not CCL21.

SIGNOR-278124

P42574

P08590

1

cleavage

down-regulates quantity by destabilization

0.377

By sequencing and site-directed mutagenesis, a noncanonical cleavage site for caspase-3 was mapped to the C-terminal DFVE(135)G motif. We demonstrated that vMLC1 cleavage in failing myocardium in vivo is associated with a morphological disruption of the organized vMLC1 staining of sarcomeres, and with a reduction in myocyte contractile performance.

SIGNOR-270593

P06213

P07550

1

phosphorylation

down-regulates activity

0.377

Insulin (10 nM)-stimulated rIR-catalyzed phosphorylation of β2-adrenergic receptor peptides was found prominently in peptides L339 (Tyr350 and Tyr354), T362 (Tyr364), and to a lesser extent peptides Y132 (Tyr132 and Tyr141), and I135 (Tyr141). G-protein-linked receptors and intrinsic tyrosine-kinase growth receptors represent two prominent modalities in cell signaling. Cross-regulation among members of both receptor superfamilies has been reported, including the counter-regulatory effects of insulin on β-adrenergic catecholamine action. Cells stimulated by insulin show loss of function and increased phosphotyrosine content of β2-adrenergic receptors.

SIGNOR-251302

Q8WZ19

P61586

1

binding

down-regulates quantity

0.377

BACURDs form ubiquitin ligase complexes, which selectively ubiquitinate RhoA, with Cul3. Our studies reveal a previously unknown mechanism for controlling RhoA degradation and regulating RhoA function in various biological contexts, which involves a Cul3/BACURD ubiquitin ligase complex.

SIGNOR-264236

Q13164

P37231

1

binding

up-regulates activity

0.377

In endothelial cells, flow-mediated activation of ERK5 has been shown to lead to activation of PPAR gamma by direct binding to the hinge-helix region of PPAR gamma

SIGNOR-278108

P12931

P84022

1

phosphorylation

up-regulates activity

0.377

Although the role of ERK in mediating phosphorylation of Smad2/3 remains to be investigated, our data indicate that early Smad3 phosphorylation is independent of transient EGFR transactivation and ERK1/2 activation initiated by HB-EGF release, whereas Src mediated chronic EGFR transactivation and ERK1/2 activation involve late Smad3 activation induced by TGF-beta1.|Inhibition of Src not only decreases Smad3 phosphorylation but also decreases phosphorylation dependent nuclear translocation of Smad2/3, suggesting that Src kinase could modulate Smad3 activity.

SIGNOR-279292

Q16659

O95551

1

phosphorylation

up-regulates activity

0.377

ERK3 phosphorylates TDP2 and promotes its phosphodiesterase activity, thereby upregualting TDP2-mediated DNA damage response and desensitizing lung cancer cells to Top2 inhibitor-induced growth inhibition.|In the current study, we have found that ERK3, an atypical MAPK, phosphorylates TDP2 at S60 and regulates TDP2 's phosphodiesterase activity, thereby cooperatively protecting lung cancer cells against Top2 inhibitors induced DNA damage and growth inhibition.

SIGNOR-278245

O15297

P13051

1

dephosphorylation

down-regulates activity

0.377

PPM1D dephosphorylation of UNG2 is correlated with reduced UNG2 activity on uracil-containing templates.|This result suggests that PPM1D specifically inhibits UNG2 and not other uracil DNA glycosylases.

SIGNOR-277156

Q8WZA2

P01308

1

relocalization

up-regulates quantity

0.377

Activation of EPAC2 has recently been shown to increase the density of insulin‐containing granules near the plasma membrane, facilitating insulin secretion from the β cells

SIGNOR-278140

P16298

P19484

1

dephosphorylation

up-regulates activity

0.377

Lysosomal Ca2+ release via mucolipin 1 (MCOLN1) activates calcineurin, which binds and de-phosphorylates TFEB, thus promoting its nuclear translocation.

SIGNOR-255306

Q9NU22

Q8IZL8

1

binding

up-regulates quantity by stabilization

0.377

MDN1 Is Physically and Functionally Associated with the Mammalian PELP1 Complex. To more specifically determine a function of mammalian MDN1 in the subnuclear distribution of PELP1-containing pre-60S-particles, we examined PELP1 localization in control cells or cells depleted from MDN1. Importantly, in the absence of MDN1, PELP1 became sequestered in enlarged nucleoli, indicating that MDN1 is involved in the nucleolar release of PELP1-containing pre-60S ribosomes

SIGNOR-261357

Q66K64

Q14498

1

polyubiquitination

down-regulates quantity by destabilization

0.377

Indisulam promotes an interaction between RBM39 and the DCAF15 E3 ligase substrate receptor, leading to RBM39 ubiquitination and proteasome-mediated degradation.

SIGNOR-272203

P62136

P38398

1

dephosphorylation

down-regulates activity

0.377

Protein kinases involved in the DNA damage checkpoint control, such as ATM, ATR, and hCds1/Chk2, have been shown to phosphorylate and activate BRCA1 upon DNA damage. |Altogether, these results indicate that PP1α specifically dephosphorylates BRCA1 at multiple serine sites, including S988 [12], S1423, and S1524.

SIGNOR-248560

Q13535

Q01094

1

phosphorylation

up-regulates quantity by stabilization

0.377

These results thus suggest that this serine 31 residue is indeed an atm/atr phosphorylation site and in fact is the major site for atm/atr-mediated phosphorylation within e2f1. Thus, it is possible that the atm/atr-mediated phosphorylation inhibits the binding and function of skp2 and thus prevents the normal degradation of e2f1

SIGNOR-109420

Q13237

P48764

1

phosphorylation

down-regulates activity

0.377

CGMP and cGKII increased NHE3 phosphorylation at three sites (rabbit Ser (554), Ser (607), and Ser (663), equivalent to mouse Ser (552), Ser (605), and Ser (659)), all of which had to be present at the same time for cGMP to inhibit NHE3.|cGMP and cGKII rapidly inhibited NHE3, which was associated with reduced surface NHE3.

SIGNOR-280096

P35452

O60675

1

binding

down-regulates activity

0.377

Hoxd12 and MHox, that interact with v-/c-Maf, using the phage display method. The Hox proteins also could associate with the other Maf protein family members, MafB, MafK, MafF, and MafG, but not with Jun and Fos. The Hox proteins negatively regulated the DNA binding, transactivation and cell-transforming abilities of Maf.

SIGNOR-221929

Q00535

P49023

1

phosphorylation

up-regulates activity

0.377

Thus, phosphorylation of paxillin is involved in NGF-induced neurite extension of PC-12 cells, probably through regulating focal adhesion organization.|cdk5 and p38MAPK phosphorylates Ser 85 on paxillin in vitro.

SIGNOR-278921

P60953

P49841

1

binding

down-regulates

0.377

Phospho-gsk3b-specific antibodies also revolved that lkb1 regulates gsk3b phosphorylation at a known inhibitory site, serine-9. This localized phosphorylation is cdc42 and pkc-zeta-dependent.

SIGNOR-119885

Q6W2J9

Q13547

1

binding

up-regulates activity

0.377

BCoR can interact w Because HDACs appear to be involved in repression by an increasing number of transcriptional repressors, we tested whether BCoR can associate with HDACs. BCoR can interact with HDAC1, HDAC3, and HDAC-B/5 more strongly than with HDAC-A/4, HDAC-C, HDAC-D, and HDAC-E.

SIGNOR-252236

Q15915

P08151

1

relocalization

up-regulates

0.377

Co-expression of zic1 resulted in gli1 and gli3 proteins being translocated to the nucleus in varying levels

SIGNOR-105491

Q9UM73

P31939

1

phosphorylation

up-regulates activity

0.377

ATIC and VASP phosphorylation is dependent on NPM-ALK kinase activity. ATIC activity is enhanced in the presence of NPM-ALK in vitro.The ATIC activity is enhanced by NPM-ALK in HEK-293T-Rex cells.

SIGNOR-276171

Q00535

P27695

1

phosphorylation

up-regulates activity

0.377

Apurinic/apyrimidinic endonuclease-1 (APE1) is a multifunctional DNA repair/gene regulatory protein in mammalian cells, and was recently reported to be phosphorylated at Thr233 by CDK5.

SIGNOR-276337

O15033

Q9NR28

1

ubiquitination

down-regulates quantity by destabilization

0.377

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

SIGNOR-267672

O95243

O15528

1

transcriptional regulation

up-regulates quantity by expression

0.377

Phosphorylation of MBD4 promotes 5-meC glycosylase activity Further evidence emerged to support the involvement of MBD4 in active demethylation. Protein-kinase C phosphorylation of MBD4 at two specific serine residues (165 and 262) following parathyroid hormone stimulation was shown to promote demethylation within the CYP27B1 gene promoter [12]

SIGNOR-275682

P24941

P62136

1

phosphorylation

down-regulates activity

0.377

Both of these pp1 isoforms contain an arg-pro-ile/val-thr-pro-pro-arg sequence near the c terminus, a known site of phosphorylation by cdc/cdk kinases, and phosphorylation attenuates phosphatase activity

SIGNOR-92265

Q96J02

Q9HBA0

1

ubiquitination

down-regulates activity

0.377

AIP4 ubiquitin ligase is involved in the ubiquitination of both TRPV4 and TRPC4.Ubiquitination of TRPV4 is dramatically increased by the HECT (homologous to E6-AP carboxyl terminus)-family ubiquitin ligase AIP4 without inducing degradation of this channel. Instead, AIP4 promotes the endocytosis of TRPV4 and decreases its amount at the plasma membrane.

SIGNOR-272625

Q99527

P63092

1

binding

up-regulates activity

0.377

GPCRs transduce their signal via G-protein heterotrimers (αβγ) that dissociate in free Gα-subunit protein and Gβγ-subunit protein complexes following ligand stimulation; the activated receptor induces a conformational change in the associated G protein α-subunit leading to release of GDP followed by binding of GTP and α-subunit dissociation from the receptor.

SIGNOR-251102

Q13131

Q09472

1

phosphorylation

down-regulates

0.376

The mechanism of ampk-mediated anti- inflammation involves the induction of p300 ser89 phosphor- ylation and subsequent inactivation of p300 hat activity.

SIGNOR-176637

O96017

P00441

1

phosphorylation

up-regulates activity

0.376

ROS signaling is mediated by Mec1/ATM and its effector Dun1/Cds1 kinase, through Dun1 interaction with Sod1 and regulation of Sod1 by phosphorylation at S60, 99. In the nucleus, Sod1 binds to the promoters and regulates the expression of oxidative resistance and repair genes.

SIGNOR-262794

P45984

P30307

1

phosphorylation

down-regulates

0.376

Here we show that jnk directly phosphorylates cdc25c at serine 168 during g(2) phase of the cell cycle. Cdc25c phosphorylation by jnk negatively regulates its phosphatase activity and thereby cdk1 activation, enabling a timely control of mitosis onset.

SIGNOR-164093

Q9Y297

Q15910

1

ubiquitination

down-regulates

0.376

_-trcp ubiquitinates ezh2 and jak2-mediated phosphorylation on y641 directs _-trcp-mediated ezh2 degradation.

SIGNOR-204481

Q9UNE7

Q16665

1

ubiquitination

down-regulates quantity by destabilization

0.376

the ubiquitin ligase activity of CHIP regulates HIF-1α degradation.

SIGNOR-271426

P53350

Q9UBW7

1

phosphorylation

down-regulates quantity by destabilization

0.376

PLK1 and HOTAIR Accelerate Proteasomal Degradation of SUZ12 and ZNF198 during Hepatitis B Virus-Induced Liver Carcinogenesis|Similar analyses with ZNF198 identified two clusters of putative Plk1 phosphorylation sites in vitro. A cluster of serine residues at the N-terminus of ZNF198, S303, S305, and S309, and a cluster at the C-terminus, S1056 and S1064. The triple Ser to Ala mutant, S303A/S305A/S309A, consistently exhibited the lowest level of phosphorylation in vitro, in comparison to the double S1056A/S1064A mutant

SIGNOR-275560

P50750

Q09472

1

phosphorylation

up-regulates activity

0.376

As Cdk9 phosphorylates both RNA polymerase II and p300 and increases p300-HAT activity , the effects of CUR and PyrC on the kinase activity of Cdk9 were examined .|As Cdk9 phosphorylates both RNA polymerase II and p300 and increases p300-HAT activity, the effects of CUR and PyrC on the kinase activity of Cdk9 were examined.

SIGNOR-279690

O14965

O43521

1

phosphorylation

down-regulates quantity by destabilization

0.376

We observed that BimEL is phosphorylated by Aurora A early in mitosis and reversed by PP2A after mitotic exit. Aurora A phosphorylation stimulated binding of BimEL to the F-box protein beta-transducin repeat containing E3 ubiquitin protein ligase and promoted ubiquitination and degradation of BimEL.

SIGNOR-276248

P35452

O15525

1

binding

down-regulates activity

0.376

Hoxd12 and MHox, that interact with v-/c-Maf, using the phage display method. The Hox proteins also could associate with the other Maf protein family members, MafB, MafK, MafF, and MafG, but not with Jun and Fos. The Hox proteins negatively regulated the DNA binding, transactivation and cell-transforming abilities of Maf.

SIGNOR-221958

Q8IXJ6

P15172

1

deacetylation

down-regulates

0.376

Sir2-mediated deacetylation of myod can be expected to inhibit its transcriptional capabilities.

SIGNOR-104251

Q13464

P35611

1

phosphorylation

up-regulates

0.376

Rho-associated kinase (rho- kinase), which is activated by the small guanosine triphosphatase rho, phosphorylates alpha-adducin and thereby enhances the f-actin-binding activity of alpha-adducin in vitro. Here we identified the sites of phosphorylation of alpha-adducin by rho-kinase as thr445 and thr480

SIGNOR-66996

Q00535

P16949

1

phosphorylation

down-regulates

0.376

Involved in the regulation of the microtubule (mt) filament system by destabilizing microtubules. Prevents assembly and promotes disassembly of microtubules. The kinases involved in phosphorylating stmn ser-16 and ser-63 include camp-dependent protein kinase (pka) and pak1, whereas stmn ser-25 and ser-38 have been shown to be targets for proline-directed serine/threonine kinases such as cyclin-dependent kinases, erk1/2, and members of the p38 mapk subfamily.

SIGNOR-166682

P45984

P49768

1

phosphorylation

up-regulates

0.376

This jnk phosphorylation of ps1 at ser(319)thr(320) enhances the stability of the ps1 c-terminal fragment that is necessary for gamma-secretase activity.

SIGNOR-179676