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
P47736	P19086	1	binding	down-regulates activity	0.35	Biochemical analysis using purified recombinant proteins revealed that the physical interaction between Gaz and Rap1GAP blocks the ability of RGSs (regulators of G protein signaling) to stimulate GTP hydrolysis of the a subunit, and also attenuates the ability of activated Gaz to inhibit adenylyl cyclase.	SIGNOR-278053
Q06418	Q13191	2	phosphorylation	up-regulates activity	0.35	To test whether phosphorylation of Cbl-b at Tyr133 and/or Tyr363 by Tyro3 is important for its ubiquitin ligase function, we examined the ubiquitination of the Cbl-b mutants and Tyro3.	SIGNOR-279577
P50148	Q06187	1	binding	up-regulates activity	0.35	AlF− 4-activated Gaq-GDP increased Btk activity as expected, whereas AlF− 4 alone had no stimulatory effect (Table 1), so we conclude that Gaq directly stimulates Btk kinase activity	SIGNOR-278083
Q13191	Q06418	2	ubiquitination	up-regulates activity	0.35	Consistent with these data, we also found that Tyro3 is ubiquitinated by Cbl-b.\|These data suggest that not only was Tyro3 a ubiquitination target of Cbl-b, but also that Cbl-b was a phosphorylation target of Tyro3.	SIGNOR-278807
P68400	P20042	1	phosphorylation	up-regulates	0.35	The n-terminal domain of the human eif2beta subunit and the ck2 phosphorylation sites are required for its function. These results suggest that ser2 and ser67 contribute to the important role of the n-terminal region of eif2beta for its function in mammals.	SIGNOR-140994
Q14164	P10914	1	phosphorylation	down-regulates activity	0.35	We demonstrated that IKK-ε phosphorylated the transcription factor IFN regulatory factor 1 (IRF-1) at amino acid (aa) 215/219/221 in primary CD4(+) T cells and blocked its transcriptional activity.	SIGNOR-276480
Q00535	Q99958	1	phosphorylation	up-regulates activity	0.35	Cdk5 phosphorylates Foxc2 and activates Foxc2 dependent transcription.	SIGNOR-279156
Q9H1C0	Q14344	1	binding	up-regulates activity	0.35	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-257284
P27361	P08235	1	phosphorylation	down-regulates quantity by destabilization	0.35	Taken together, these data suggest that ERK1/2 directly phosphorylates the MR on several serine residues present in its NTD, that the upward shift of MR is mainly due to receptor phosphorylation, and finally that these sites represent the major aldosterone-inducible targets for MR phosphorylation.MR phosphorylation limits the transcriptional activity.Taken together, these results provide evidence that MR phosphorylation plays a role in aldosterone-mediated ubiquitylation and degradation.	SIGNOR-276102
P12931	P11511	1	phosphorylation	up-regulates	0.35	Phosphorylation of the 361-tyrosine residue is crucial in the up-regulation of aromatase activity. c-src protein directly phosphorylates aromatase on tyrosine 361.	SIGNOR-186284
Q8TEL6	P01106	1	binding	down-regulates quantity by destabilization	0.35	We characterize a new Myc-interacting factor, TRPC4AP (transient receptor potential cation channel, subfamily C, member 4-associated protein)/TRUSS (tumor necrosis factor receptor-associated ubiquitous scaffolding and signaling protein), which is the receptor for a DDB1 (damage-specific DNA-binding protein 1)-CUL4 (Cullin 4) E3 ligase complex for selective Myc degradation through the proteasome. TRPC4AP/TRUSS binds specifically to the Myc C terminus and promotes its ubiquitination and destruction through the recognition of evolutionarily conserved domains in the Myc N terminus.	SIGNOR-271963
Q9UHC7	P11940	1	ubiquitination	up-regulates activity	0.35	We show that MKRN1 directly binds to the cytoplasmic poly(A)-binding protein (PABPC1) and associates with polysomes. MKRN1 is positioned upstream of poly(A) tails in mRNAs in a PABPC1-dependent manner. Ubiquitin remnant profiling and in vitro ubiquitylation assays uncover PABPC1 and ribosomal protein RPS10 as direct ubiquitylation substrates of MKRN1.Our data show that MKRN1 associates with polysomes and ubiquitylates RPS10, indicating a role in translational control. We hypothesize that ribosomes encountering the MKRN1-PABPC1 complex are stalled, possibly via ubiquitylation of RPS10 on K107 and other MKRN1 substrates.	SIGNOR-272215
Q9Y625	Q13635	1	binding	up-regulates activity	0.35	Based on results from in vitro experiments, we had previously proposed that GPC6 stimulates Hh signaling by interacting with Hh and Patched1 (Ptc1), and facilitating/stabilizing their interaction.	SIGNOR-264031
P06241	Q96PD2	1	phosphorylation	up-regulates activity	0.35	Mutagenesis analysis of ESDN's seven intracellular tyrosines in YxxP motifs found several contribute to the binding of ESDN to the SH2 domains of both CrkCT10 regulator of kinase Crk-Like (CrkL) and a representative SFK Fyn. Quantitative mass spectrometry showed that at least three of these (Y565, Y621 and Y750), as well as non-YxxP Y715, are reversibly phosphorylated. SFK activity was shown to be sufficient, but not required for the interaction between ESDN and the CrkL-SH2 domain. Finally, antibody-mediated ESDN clustering induces ESDN tyrosine phosphorylation and CrkL-SH2 binding.	SIGNOR-273946
P67775	P56524	1	dephosphorylation	up-regulates	0.35	Different signal-regulated serine/threonine kinases phosphorylate class ii histone deacetylases (hdacs) to promote nuclear export, cytosolic accumulation, and activation of gene transcriptionhere we show that hdac4 forms a complex with the pp2a holoenzyme c alpha, a alpha, b/pr55 alpha. In vitro and in vivo binding studies demonstrate that the n-terminus of hdac4 interacts with the catalytic subunit of pp2a. Hdac4 is dephosphorylated by pp2a	SIGNOR-159492
O75487	P56704	1	binding	up-regulates	0.35	Gpc4 bound to wnt3a and wnt5a which activate the beta-catenin-dependent and -independent pathways, respectively, and colocalized with wnts on the cell surface. Expression of gpc4 enhanced the wnt3a-dependent beta-catenin pathway and the wnt5a-dependent beta-catenin-independent pathway, and knockdown of gpc4 suppressed both pathways	SIGNOR-195749
P68400	P35659	1	phosphorylation	up-regulates	0.35	Dek is phosphorylated by the protein kinase ck2 in vitro and in vivo on ser32	SIGNOR-125912
Q15418	P50549	1	phosphorylation	up-regulates activity	0.35	Here we describe that the 90-kDa ribosomal S6 kinase 1 (RSK1), a protein kinase downstream of the extracellular signal-regulated kinase (ERK) subclass of MAPKs, binds to ER81, phosphorylates it, and enhances ER81-dependent transcription. Two in vivo RSK1 phosphorylation sites within ER81, Ser(191) and Ser(216), were identified, whose mutation to alanine reduces ER81 activity upon ERK-MAPK stimulation.	SIGNOR-249163
P51608	Q13224	1	transcriptional regulation	down-regulates quantity by repression	0.35	The interaction of MeCP2 with the 2BI3 and 2BI5 sites was strikingly reduced in neurons maintained in the presence of TTX (Fig. 2C). This result is consistent with the classical view of MeCP2 as a general transcriptional repressor, in that the reduced association leads to increased expression of NR2B.	SIGNOR-264685
P05412	O94925	1	transcriptional regulation	up-regulates quantity by expression	0.35	The transcription factor c-Jun can directly bind to the GLS gene promoter and enhance expression	SIGNOR-268035
Q14832	P63092	1	binding	up-regulates activity	0.35	MGluRs are members of the G-protein-coupled receptor (GPCR) superfamily, the most abundant receptor gene family in the human genome. GPCRs are membrane-bound proteins that are activated by extracellular ligands such as light, peptides, and neurotransmitters, and transduce intracellular signals via interactions with G proteins. The resulting change in conformation of the GPCR induced by ligand binding activates the G protein, which is composed of a heterotrimeric complex of α, β, and γ subunits.	SIGNOR-264083
Q86YT6	Q9NYJ7	1	ubiquitination	up-regulates activity	0.35	Mib physically interacts with Delta and promotes its ubiquitination and internalization [66], which have been shown to up-regulate Notch activity.	SIGNOR-209672
Q96J02	Q9UBN4	1	ubiquitination	down-regulates activity	0.35	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-272624
Q13829	P61586	1	binding	down-regulates quantity	0.35	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-264235
P17612	P17752	1	phosphorylation	up-regulates activity	0.35	The activation of tryptophan hydroxylase by protein kinase A is mediated by the phosphorylation of serine-58 within the regulatory domain of the enzyme.	SIGNOR-250062
O14965	Q8TEW0	1	phosphorylation	up-regulates	0.35	Aurora a interacts directly with the atypical protein kinase c binding domain of par3 and phosphorylates it at serine 962. The phosphorylation of par3 at serine 962 contributes to its function in the establishment of neuronal polarity.	SIGNOR-188398
Q13164	Q92886	1	phosphorylation	up-regulates activity	0.35	Activation of ERK5 potentiates while inhibition of ERK5 attenuates Neurog1 stimulated neurogenesis.\|ERK5 directly phosphorylated Neurog1 in vitro and modulated the transcriptional and pro-neural activity of Neurog1 in cortical progenitors.	SIGNOR-278364
P51955	Q8N137	1	phosphorylation	down-regulates activity	0.35	The opposite outcomes in NEK2- and centrobin-depleted cells suggest that NEK2 antagonizes biological functions of centrobin.\|These results suggest that NEK2 phosphorylates specific sites of centrobin, which are distinct from the PLK1 phosphorylation sites.	SIGNOR-279545
Q96QE3	O60885	1	binding	up-regulates	0.35	ATAD5 Interacts with BRD4 through a Conserved BET Protein-Binding Domain. BRD4-ATAD5 binds to acetyl-histones in nascent chromatin. BRD4 release from chromatin correlates with PCNA unloading. Disruption of the interaction between BRD4 and acetyl-histones or between BRD4 and ATAD5 reduces the PCNA amount on chromatin.	SIGNOR-266412
P06493	Q06830	1	phosphorylation	down-regulates	0.35	Peroxiredoxin (prx) i is a member of the peroxiredoxin family of peroxidases and contains a consensus site (thr(90)-pro-lys-lys) for phosphorylation by cyclin-dependent kinases (cdks). This protein has now been shown to be phosphorylated specifically on thr(90) by several cdks, including cdc2, in vitro. Phosphorylation of prx i on thr(90) reduced the peroxidase activity of this protein by 80%.	SIGNOR-87097
P03956	P02461	1	cleavage	down-regulates quantity by destabilization	0.35	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-272339
P06241	Q9HBA0	1	phosphorylation	up-regulates activity	0.35	ROS could be detected by Fyn, which is required to activate TRPV4 in a redox-sensitive manner.\|The Ca 2+ response to H 2 O 2 required the basal phosphorylation of TRPV4 by the Src kinase Fyn, which may serve as the redox sensor responsible for TRPV4 activation (Figure 2 ) [220] , and was able to increase barrier permeability [219] .	SIGNOR-279991
P06493	P11387	1	phosphorylation	up-regulates activity	0.349	In vitro kinase assays demonstrated that Ser(10) can be phosphorylated by casein kinase II, Ser(21) can be phosphorylated by protein kinase Calpha, and Ser(112) and Ser(394) can be phosphorylated by Cdk1.Collectively these results indicate that topo I is phosphorylated during mitosis at multiple sites, one of which enhances DNA relaxation activity in vitro and interaction with DNA in cells.	SIGNOR-276157
P20742	P14780	2	binding	down-regulates activity	0.349	Both PZP and a2M collagenase complexes incubated with gelatin demonstrated a significant inhibition of the catalytic activity\| MMP-2 and MMP-9 cause a significant degradation of these bands and the background, a degradation which is prevented by both a2M and PZP.	SIGNOR-261802
P17252	P10415	1	phosphorylation	up-regulates	0.349	Purified pkca can efficiently and directly phosphorylate bcl2 at serine 70	SIGNOR-60120
P48436	P32243	1	binding	up-regulates activity	0.349	BEST1 promoter activity was increased by SOX9 overexpression and decreased by siRNA-mediated SOX9 knockdown. SOX9 physically interacted with MITF and OTX2 and orchestrated synergistic activation of the BEST1 promoter with the paired SOX site playing essential roles.	SIGNOR-255184
P17612	Q14103	1	phosphorylation	up-regulates	0.349	Protein kinase a enhances, whereas glycogen synthase kinase-3 beta inhibits, the activity of the exon 2-encoded transactivator domain of heterogeneous nuclear ribonucleoprotein d in a hierarchical fashion.	SIGNOR-116144
Q969H0	Q96KS0	1	ubiquitination	down-regulates quantity by destabilization	0.349	Mechanistically, we further show that FBW7, an E3 ligase complex component that is frequently downregulated in TNBC, negatively regulates EglN2 protein stability.	SIGNOR-261997
Q16513	O15553	1	phosphorylation	down-regulates activity	0.349	PKNs bind to human pyrin and phosphorylate S208 and S242. Pyrin forms an inflammasome when mutant or in response to bacterial modification of the GTPase RhoA. We found that RhoA activated the serine-threonine kinases PKN1 and PKN2 that bind and phosphorylate pyrin. Phosphorylated pyrin bound to 14-3-3 proteins, regulatory proteins that in turn blocked the pyrin inflammasome.	SIGNOR-275464
P49841	Q7KZI7	1	phosphorylation	down-regulates activity	0.349	MARK family kinases can be activated by phosphorylation of a conserved threonine (Thr-208 in MARK2), and inactivated by phosphorylation of a serine (Ser-212), both in the activation loop of the catalytic domain. Activation is achieved by the kinases MARKK/TAO1 or LKB1, although the inactivating kinase was unknown. We show here that GSK3beta serves the role of the inhibitory kinase.	SIGNOR-276163
Q04759	Q00613	1	phosphorylation	up-regulates	0.349	At the same time, ea causes pkc?-Mediated phosphorylation and activation of the transcription factor heat shock factor 1, an inducer of glucose dependence.	SIGNOR-200576
O14829	O14737	1	dephosphorylation	down-regulates quantity by destabilization	0.349	Here, we report that the serine/threonine phosphatase PPEF-1 interacts with and dephosphorylates PDCD5 at Ser 119, which leads to PDCD5 destabilization.\|These results demonstrate that PPEF-1 reduces PDCD5 stability via PDCD5 dephosphorylation.	SIGNOR-277008
O14713	P16144	1	binding	down-regulates activity	0.349	Integrins also bind to many PTBdomain-containing proteins (Calderwood et al., 2003) – including Dok1 and integrincytoplasmic-domain-associated protein 1 (ICAP1) – and these can compete with talin for binding to integrin and so can impair activation	SIGNOR-257658
P14780	P20742	2	cleavage	down-regulates quantity by destabilization	0.349	The complex formation was confirmed by the use of 125I-labeled matrix metalloproteinase-2. The cleavage sites in the "bait" regions following formation of high-molecular-weight complexes of matrix metalloproteinases with the alpha-macroglobulins were determined by protein sequence analysis. Pregnancy zone protein was cleaved at Thr693-Tyr694 and alpha2-macroglobulin at Gly679-Leu680 and Arg696-Leu697 by matrix metalloproteinase-2. Matrix metalloproteinase-9 cleaved alpha2-macroglobulin at the same site as matrix metalloproteinase-2, but cleavage of pregnancy zone protein was at Leu753-Ser754.\|MMP-2 and MMP-9 cause a significant degradation of these bands and the background, a degradation which is prevented by both a2M and PZP.	SIGNOR-261785
Q8TCY5	Q01726	1	binding	down-regulates activity	0.349	We report that MRAP and MRAP2 can interact with all 5 MCRs. This interaction results in MC2R surface expression and signaling. In contrast, MRAP and MRAP2 can reduce MC1R, MC3R, MC4R, and MC5R responsiveness to [Nle4,D-Phe7]alpha-melanocyte-stimulating hormone (NDP-MSH). MRAP and MRAP2 can reduce the surface expression of MC4R and also the signaling of this receptor. we observed a significant decrease in the cell-surface expression of MC4R and MC5R in the presence of MRAP and MRAP2. It is interesting that MRAP and MRAP2 have opposite effects in the modulation of different MCR family members.	SIGNOR-252364
Q00987	P46695	1	ubiquitination	down-regulates quantity by destabilization	0.349	FHL2 stimulates MDM2 mediated ubiquitination of IER3 by forming a ternary complex.\|Scaffold protein FHL2 facilitates MDM2 mediated degradation of IER3 to regulate proliferation of cervical cancer cells.	SIGNOR-278824
P06239	Q13444	1	phosphorylation	up-regulates	0.349	Hck, and to a lesser extent lck, phosphorylated the adam15. Deletion and point mutation analysis of the adam15 cytoplasmic domain confirmed the importance of the proline-rich motifs for grb2 and lck binding and indicated the regulatory nature of tyr(715) and tyr(735). These data demonstrate selective, phosphorylation-dependent interactions of adam15 with src family ptks and grb2, which highlight the potential for integration of adam functions and cellular signaling.	SIGNOR-112931
P28223	P63096	1	binding	up-regulates activity	0.349	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-256742
O96017	P61289	1	phosphorylation	up-regulates activity	0.349	REGγ interacts with DBC1 and is phosphorylated by Chk2.	SIGNOR-273611
Q5VWQ8	O60674	1	binding	down-regulates activity	0.349	In vascular smooth muscle cells (VSMCs) treated with IFN-γ, DAB2IP directly binds to JAK2 and inhibits its kinase activity, limiting JAK-dependent STAT1/3 and PI3K–AKT phosphorylation and activation	SIGNOR-254760
Q9UM11	O00429	1	ubiquitination	down-regulates quantity	0.349	Here we demonstrate that changes in mitochondrial dynamics as cells exit mitosis are driven in part through ubiquitylation of Drp1 catalyzed by the APC/Ccdh1 (anaphase-promoting complex/cyclosome and its coactivator (Cdh1) E3 ubiquiting ligase complex	SIGNOR-274127
P08172	P09471	1	binding	up-regulates activity	0.349	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-256964
P49137	P53350	1	phosphorylation	up-regulates	0.349	Here, we have identified mk2 as a major plk1 kinase toward ser326, whose phosphorylation is critical to recruit ?-Tubulin to centrosomes and subsequent establishment of functional bipolar spindles. To our knowledge, this is the first direct evidence to demonstrate that the essential function of plk1 in centrosome maturation and bipolar spindle formation is controlled by its upstream kinase.	SIGNOR-179968
Q05086	P78352	1	ubiquitination	down-regulates quantity by destabilization	0.349	E6-induced degradation of DLG4 depends on E6AP in vivo. Our findings as a whole indicate that E6AP is involved in E6-mediated ubiquitination and degradation of DLG4 both in vivo and in vitro.	SIGNOR-271397
Q13315	Q99607	1	phosphorylation	down-regulates activity	0.349	Elf4 is phosphorylated by Atm after gamma irradiation, leading to its degradation.\|Thus, Atm promotes Elf4 protein degradation after gamma irradiation via phosphorylation at these sites.	SIGNOR-278466
Q8N1E6	P01106	1	ubiquitination	down-regulates quantity by destabilization	0.349	In this study, we demonstrate that the deubiquitinase USP13 stabilizes c-Myc by antagonizing FBXL14-mediated ubiquitination to maintain GSC self-renewal and tumorigenic potential. USP13 was preferentially expressed in GSCs, and its depletion potently inhibited GSC proliferation and tumor growth by promoting c-Myc ubiquitination and degradation.	SIGNOR-274125
Q7Z5G4	P01112	1	palmitoylation	up-regulates activity	0.349	Covalent lipid modifications mediate the membrane attachment and biological activity of Ras proteins. All Ras isoforms are farnesylated and carboxyl-methylated at the terminal cysteine; H-Ras and N-Ras are further modified by palmitoylation. Here we report that H- and N-Ras are palmitoylated by a human protein palmitoyltransferase encoded by the ZDHHC9 and GCP16 genes. DHHC9 is an integral membrane protein that contains a DHHC cysteine-rich domain. GCP16 encodes a Golgi-localized membrane protein.	SIGNOR-261351
Q13153	P17600	1	phosphorylation	up-regulates activity	0.349	Synapsin I is phosphorylated at Ser603 by p21-activated kinases. the Ser603 residue must be one of the pivotal sites for the release	SIGNOR-250235
Q9H4B4	Q16665	1	phosphorylation	down-regulates	0.348	Polo-like kinase 3 functions as a tumor suppressor and is a negative regulator of hypoxia-inducible factor-1 alpha under hypoxic conditionsplk3 can potentially inhibit hif-1_ by physical interaction and direct phosphorylation	SIGNOR-178743
P19784	Q00613	1	phosphorylation	up-regulates	0.348	Transcriptional activity and dna binding of heat shock factor-1 involve phosphorylation on threonine 142 by ck2.As hsf1 is activated by heat shock simultaneously with the nuclear translocation of the protein kinase ck2, we have investigated the role of ck2 in hsf1 activatio	SIGNOR-99606
P68400	O95863	1	phosphorylation	up-regulates quantity by stabilization	0.348	Serines 11 and 92 participate in the control of snail1 stability and positively regulate snail1 repressive function and its interaction with msin3a corepressor. Furthermore, serines 11 and 92 are required for snail1-mediated emt and cell viability, respectively. Pka and ck2 have been characterized as the main kinases responsible for in vitro snail1 phosphorylation at serine 11 and 92, respectively.	SIGNOR-161771
Q05655	P41594	1	phosphorylation	up-regulates activity	0.348	Thus, we showed that it is phosphorylation of Ser-839, not Thr-840, that is absolutely required for the unique Ca2+ oscillations produced by mGluR5 activation. The Thr-840 residue is important only in that it is permissive for the PKC-dependent phosphorylation of Ser-839.	SIGNOR-249287
Q9UEW8	Q9Y6R1	1	phosphorylation	down-regulates activity	0.348	SPAK phosphorylates the transporters to reduce their surface expression and thus their activity and consequently inhibits ductal secretion to stabilize the resting state. PP1 reverses the effect of SPAK. Molecular analysis revealed that the WNK kinases acted as scaffolds to recruit SPAK, which phosphorylated CFTR and NBCe1-B, reducing their cell surface expression.	SIGNOR-263133
Q96J02	Q16625	1	ubiquitination	down-regulates quantity by destabilization	0.348	Two mechanisms regarding junction protein turnover were illustrated in this process, that is, the Itch-induced occludin ubiquitination and proteasome degradation, and the caveolae-dependent endocytosis of junction proteins (JAM-A, N-cadherin, and \u03b2 -catenin), both of which led to the instability of junction apparatus between adjacent SCs and a subsequent damaged BTB.	SIGNOR-278756
P06493	O15297	1	phosphorylation	down-regulates quantity by destabilization	0.348	Phosphorylation of multiple residues in the catalytic domain of PPM1D during mitosis, including Ser40 by Cyclin-dependent kinase 1 (CDK1), leads to ubiquitination of PPM1D and subsequent proteasomal degradation by Adenomatous polyposis coli (APC) and cell-division cycle protein 20 (CDC20)	SIGNOR-275489
P11309	P30307	1	phosphorylation	up-regulates activity	0.348	First, Pim-1 activates the Cdc25C phosphatase directly through phosphorylation, very probably at the N-terminal part of the protein.\|We find that phosphorylation by Pim-1 enhances the phosphatase activity of Cdc25C and in transfected cells that are arrested in G2/M by bleomycin, Pim-1 can enhance progression into G1.	SIGNOR-278298
Q7Z553	Q9NPF5	1	binding	up-regulates quantity by stabilization	0.348	The anti-tumorigenic effect of MDGA2 was mediated through direct stabilising of DNA methyltransferase 1 associated protein 1 (DMAP1), which played a tumour suppressive role in gastric cancer. MDGA2 expression and MG132 treatment increased the level of DMAP1, suggesting that the MDGA2–DMAP1 interaction stabilises DMAP1 by inhibiting its ubiquitin-mediated degradation.	SIGNOR-264240
P60763	Q99828	1	binding	up-regulates activity	0.348	We here report that CIB, a protein that binds to the alpha(IIb)beta(3) fibrinogen receptor, interacts exclusively with activated (V12) Rac3 but not Rac1 or Rac2. Binding of V12Rac3 to CIB was mediated by the C-terminal end of Rac3 and by Rac3 membrane localization	SIGNOR-269060
O43187	Q07955	1	phosphorylation	down-regulates activity	0.348	IRAK2 phosphorylates SRSF1 and thereby reduces SRSF1 binding to the target mRNAs.	SIGNOR-278406
Q02763	P35590	1	phosphorylation	up-regulates activity	0.348	Thus, Tie2 was able to induce Tie1 phosphorylation.\|When cotransfected, Tie2 formed heteromeric complexes with Tie1, enhanced Tie1 activation, and induced phosphorylation of a kinase-inactive Tie1 in a ligand-dependent manner.	SIGNOR-279769
P22455	P42224	1	phosphorylation	up-regulates activity	0.348	Activation of Stat1 and Stat3 by FGFR derivatives. Lysates of 293T cells transfected as indicated were analysed by Western blotting using Phospho-Stat1 (Y701) antisera (top) or Stat1 antisera (bottom). (b) The same lysates in (a) were re-examined for phosphorylated Stat3 by Western blotting with Phospho-Stat3 (Y705) (top). all three FGFR family members examined here are able to lead to Stat activation. Expression of the 'TDII-like' derivatives of FGFR1, FGFR3, and FGFR4, as well as myrR1-WT, led to phosphorylation of both Stat1 and Stat3.	SIGNOR-251141
P17252	Q13507	1	phosphorylation	down-regulates	0.348	There are two known phosphorylation-mediated inactivation mechanisms for trpc3 channels. Protein kinase g (pkg) inactivates trpc3 by direct phosphorylation on thr-11 and ser-263 of the trpc3 proteins, and protein kinase c (pkc) inactivates trpc3 by phosphorylation on ser-712.	SIGNOR-130269
P49593	Q16566	1	dephosphorylation	down-regulates activity	0.348	Calmodulin-dependent protein kinase phosphatase (CaMKP) dephosphorylates and concomitantly deactivates multifunctional Ca(2+)/calmodulin-dependent protein kinases , such as CaMKI, CaMKII, and CaMKIV.	SIGNOR-277157
Q96A56	Q9H492	1	binding	up-regulates	0.348	Tp53inp1-lc3 interaction occurs via a functional lc3-interacting region (lir).	SIGNOR-196670
Q9UBF6	P46527	1	ubiquitination	down-regulates activity	0.348	SAG (Sensitive to Apoptosis Gene), also known as RBX2 (RING box protein 2), ROC2 (Regulator of Cullins 2), or RNF7 (RING Finger Protein 7), was originally cloned in our laboratory as a redox inducible antioxidant protein and later characterized as the second member of the RBX/ROC RING component of the SCF (SKP1-CUL-F-box Proteins) E3 ubiquitin ligase. by forming a complex with other components of the SCF E3 ligase, SAG promotes ubiquitination and degradation of a number of protein substrates, including c-JUN, DEPTOR, HIF-1α, IκBα, NF1, NOXA, p27, and procaspase-3, thus regulating various signaling pathways and biological processes.	SIGNOR-271447
P31751	Q9UBK2	1	phosphorylation	down-regulates	0.348	Here we describe a mechanism by which insulin, through the intermediary protein kinase akt2/protein kinase b (pkb)-beta, elicits the phosphorylation and inhibition of the transcriptional coactivator peroxisome proliferator-activated receptor-coactivator 1alpha (pgc-1alpha), a global regulator of hepatic metabolism during fasting / phosphorylation of pgc-1? At ser?570 Is required for akt to inhibit recruitment of pgc-1? To chromatin.	SIGNOR-155536
P49841	P11388	1	phosphorylation	down-regulates quantity by destabilization	0.348	This study also reports the novel finding that topoIIα may be a target of GSK3β phosphorylation. Evidence suggests that CK2 serves as a priming kinase, through phosphorylation at Ser1365, for GSK3β-mediated phosphorylation at Ser1361.	SIGNOR-276301
P50053	P60891	1	phosphorylation	up-regulates activity	0.348	Ketohexokinase-A (KHK-A; also known as fructokinase-A) phosphorylates PRPS1 T225 and activates PRPS1 by blocking the binding of ADP, AMP, and GDP, which is required for hepatocellular carcinoma development	SIGNOR-265735
P00519	Q9Y6Q9	1	phosphorylation	up-regulates	0.348	Tyrosine phosphorylation of the nuclear receptor coactivator aib1/src-3 is enhanced by abl kinase and is required for its activity in cancer cellstyrosine kinase directly phosphorylates aib1/src-3 at y1357 and modulates the association of aib1 with c-abl, eralpha, the transcriptional cofactor p300,	SIGNOR-180571
P20749	O15379	1	binding	up-regulates	0.348	We show that bcl-3 is a substrate for the protein kinase gsk3 and that gsk3-mediated bcl-3 phosphorylation, which is inhibited by akt activation, targets its degradation through the proteasome pathway. This phosphorylation modulates its association with hdac1, 3 and 6.	SIGNOR-129804
P05771	P06730	1	phosphorylation	up-regulates	0.348	Phosphorylation of eIF-4E on serine 209 by protein kinase C is inhibited by the translational repressors, 4E-binding proteins.[..] This suggests a two-step model for the phosphorylation (and activation) of eIF4E by growth factors and hormones: first, dissociation of eIF4E .	SIGNOR-248946
P07900	Q9HC29	1	binding	up-regulates quantity by stabilization	0.348	Nod2 is constitutively associated with a chaperone protein, Hsp90, which is required for Nod2 stability and protects Nod2 from degradation.	SIGNOR-252414
P42574	O75475	1	cleavage	down-regulates	0.348	Ledgf/ p75 has a cooh-terminally truncated splice variant, p52 / during apoptosis, caspase-3 cleaved p52 to generate a p38 fragment that lacked the nh2-terminal pwwp domain and failed to transactivate the hsp27 promoter in reporter assays. However, p38 retained chromatin association properties and repressed the transactivation potential of ledgf/p75	SIGNOR-180144
P43405	Q92918	1	phosphorylation	up-regulates activity	0.348	BCR ligation induced rapid tyrosine-phosphorylation of HPK1 mainly by Syk and Lyn, resulting in its association with BASH and catalytic activation. BCR-mediated activation of HPK1 was impaired in Syk- or BASH-deficient B cells. The functional SH2 domain of BASH and Tyr-379 within HPK1 which we identified as a Syk-phosphorylation site were both necessary for interaction of both proteins and efficient HPK1 activation after BCR stimulation.	SIGNOR-246567
Q9UNH5	P48200	1	dephosphorylation	up-regulates activity	0.348	IRP2 Ser-157 is phosphorylated by Cdk1/cyclin B1 during G(2)/M and is dephosphorylated during mitotic exit by the phosphatase Cdc14A. Ser-157 phosphorylation during G(2)/M reduces IRP2 RNA-binding activity and increases ferritin synthesis, whereas Ser-157 dephosphorylation during mitotic exit restores IRP2 RNA-binding activity and represses ferritin synthesis.	SIGNOR-248829
P12931	P08559	1	phosphorylation	down-regulates activity	0.348	Src inactivated PDH through direct phosphorylation of tyrosine-289 of PDH E1α subunit (PDHA1).	SIGNOR-277204
P46734	Q9Y463	1	phosphorylation	up-regulates	0.348	Mkk3 enhanced mirk kinase activity. Mkk3 possibly activates mirk by phosphorylating it.	SIGNOR-86731
Q9NYY3	P05067	1	phosphorylation	up-regulates activity	0.348	Here we show that Polo-like kinase 2 (Plk2), an activity-inducible regulator of homeostatic plasticity, directly binds and phosphorylates threonine-668 and serine-675 of APP in\u00a0vitro and associates with APP in\u00a0vivo.\|Plk2 was necessary and sufficient to induce BACE-1-mediated APP amyloidogenic processing following overexcitation, associated intimately with APP, and directly phosphorylated the APP C-terminus.	SIGNOR-279424
P61586	Q14192	1	relocalization	up-regulates	0.348	Here, we show that stimulation of the rho pathway induces translocation of the transcriptional lim-only coactivator fhl2 to the nucleus and subsequent activation of fhl2- and androgen receptor-dependent genes.	SIGNOR-114071
Q05513	P55211	1	phosphorylation	down-regulates	0.348	Inhibitor sensitivity and interactions with caspase 9 indicate that the predominant kinase that targets ser144 is the atypical protein kinase c isoform zeta (pkczeta).	SIGNOR-141629
P12931	P42681	1	phosphorylation	up-regulates activity	0.348	We further demonstrate that Rlk can be phosphorylated and activated by Src kinases, leading to a decrease in its half-life. A specific tyrosine in the activation loop of Rlk, Y420, is required for phosphorylation and activation, as well as for decreased stability, but is not required for lipid RAFT association.	SIGNOR-247346
P68400	P27348	1	phosphorylation	down-regulates activity	0.347	The neuroprotective effect of 14-3-3theta against rotenone toxicity is dependent on the inhibition of the pro-apoptotic factor Bax\|Phosphorylation at S232 induced by rotenone is reduced by casein kinase inhibitors, and is not dependent on alphasyn.\| The S232D mutant partially reduced the ability of 14-3-3theta to inhibit Bax activation in response to rotenone. Based on these findings, we propose that phosphorylation of 14-3-3s at serine 232 contributes to the neurodegenerative process in PD.	SIGNOR-264405
Q9HC98	O95235	1	phosphorylation	down-regulates activity	0.347	We show that Nek9, Nek6, and the kinesin Mklp2 form a signaling module, which is required for Mklp2 to localize to the central spindle in anaphase. Nek6 also phosphorylates Mklp2 at Ser244, inhibiting its bundling activity until anaphase onset.	SIGNOR-273891
Q9Y6Y8	Q15437	1	binding	up-regulates activity	0.347	The results showed that the N-terminal region of p125 is important for the interaction with Sec23p. We confirmed the interaction between the two proteins by a yeast two-hybrid assay. Overexpression of p125, like that of mammalian Sec23p, caused disorganization of the endoplasmic reticulum-Golgi intermediate compartment and Golgi apparatus, suggesting its role in the early secretory pathway.	SIGNOR-265306
P36508	P17987	1	transcriptional regulation	up-regulates quantity by expression	0.347	The transcription from the minimalCcta promoter was up-regulated 3-fold by ZNF143 and 6-fold by ZNF76 when full-length proteins were co-expressed, indicating that both ZNF143 and ZNF76 can enhance Ccta transcription.	SIGNOR-266221
Q92793	P48551	1	acetylation	up-regulates activity	0.347	By binding to IFNalphaR2 within the region where two adjacent proline boxes bear phospho-Ser364 and phospho-Ser384, CBP acetylates IFNalphaR2 on Lys399, which in turn serves as the docking site for interferon regulatory factor 9 (IRF9)RF9 interacts with the acetyl-Lys399 motif by means of its IRF homology2 (IH2) domain, leading to formation of the ISGF3 complex that includes IRF9, STAT1, and STAT2.	SIGNOR-217783
P11362	Q15118	1	phosphorylation	up-regulates	0.347	Mitochondrial pdhk1 is tyrosine phosphorylated and activated by fgfr1 in cancer cells further mass spectrometric analysis identified three tyrosine residues of pdhk1, including y136, y243 and y244, that are phosphorylated by fgfr1	SIGNOR-193454
P49759	P18031	1	phosphorylation	up-regulates activity	0.347	The CLK family kinases, CLK1 and CLK2, phosphorylate and activate the tyrosine phosphatase, PTP-1B. \| although CLK1 and CLK2 directly phosphorylate PTP-1B on both Ser50 and Ser242/Ser243, the preferred CLK phosphorylation site is Ser50, as it is preferentially phosphorylated at an approximate ratio of 9:1 over the Ser242/Ser243 site.	SIGNOR-250773
Q9UQM7	Q86UR5	1	phosphorylation	up-regulates	0.347	Two serine residues in rim1 (ser-241 and ser-287) and one serine residue in rim2 (ser-335) were required for 14-3-3 binding. Incubation with ca2+/calmodulin-dependent protein kinase ii greatly stimulated the interaction of recombinant n-terminal rim but not the s241/287a mutant with 14-3-3,	SIGNOR-103890
P05981	P08709	1	cleavage	up-regulates activity	0.347	Hepsin, a putative membrane-associated serine protease, activates human factor VII and initiates a pathway of blood coagulation on the cell surface leading to thrombin formation\|In contrast, an activation cleavage site factor VII mutant, R152E factor VII, was not cleaved by hepsin-transfected cells, suggesting that factor VII and S344A factor VII were activated on these cells by cleavage of the Arg152-Ile153 peptide bond. I	SIGNOR-263638

P47736

P19086

1

binding

down-regulates activity

0.35

Biochemical analysis using purified recombinant proteins revealed that the physical interaction between Gaz and Rap1GAP blocks the ability of RGSs (regulators of G protein signaling) to stimulate GTP hydrolysis of the a subunit, and also attenuates the ability of activated Gaz to inhibit adenylyl cyclase.

SIGNOR-278053

Q06418

Q13191

2

phosphorylation

up-regulates activity

0.35

To test whether phosphorylation of Cbl-b at Tyr133 and/or Tyr363 by Tyro3 is important for its ubiquitin ligase function, we examined the ubiquitination of the Cbl-b mutants and Tyro3.

SIGNOR-279577

P50148

Q06187

1

binding

up-regulates activity

0.35

AlF− 4-activated Gaq-GDP increased Btk activity as expected, whereas AlF− 4 alone had no stimulatory effect (Table 1), so we conclude that Gaq directly stimulates Btk kinase activity

SIGNOR-278083

Q13191

Q06418

2

ubiquitination

up-regulates activity

0.35

Consistent with these data, we also found that Tyro3 is ubiquitinated by Cbl-b.|These data suggest that not only was Tyro3 a ubiquitination target of Cbl-b, but also that Cbl-b was a phosphorylation target of Tyro3.

SIGNOR-278807

P68400

P20042

1

phosphorylation

up-regulates

0.35

The n-terminal domain of the human eif2beta subunit and the ck2 phosphorylation sites are required for its function. These results suggest that ser2 and ser67 contribute to the important role of the n-terminal region of eif2beta for its function in mammals.

SIGNOR-140994

Q14164

P10914

1

phosphorylation

down-regulates activity

0.35

We demonstrated that IKK-ε phosphorylated the transcription factor IFN regulatory factor 1 (IRF-1) at amino acid (aa) 215/219/221 in primary CD4(+) T cells and blocked its transcriptional activity.

SIGNOR-276480

Q00535

Q99958

1

phosphorylation

up-regulates activity

0.35

Cdk5 phosphorylates Foxc2 and activates Foxc2 dependent transcription.

SIGNOR-279156

Q9H1C0

Q14344

1

binding

up-regulates activity

0.35

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-257284

P27361

P08235

1

phosphorylation

down-regulates quantity by destabilization

0.35

Taken together, these data suggest that ERK1/2 directly phosphorylates the MR on several serine residues present in its NTD, that the upward shift of MR is mainly due to receptor phosphorylation, and finally that these sites represent the major aldosterone-inducible targets for MR phosphorylation.MR phosphorylation limits the transcriptional activity.Taken together, these results provide evidence that MR phosphorylation plays a role in aldosterone-mediated ubiquitylation and degradation.

SIGNOR-276102

P12931

P11511

1

phosphorylation

up-regulates

0.35

Phosphorylation of the 361-tyrosine residue is crucial in the up-regulation of aromatase activity. c-src protein directly phosphorylates aromatase on tyrosine 361.

SIGNOR-186284

Q8TEL6

P01106

1

binding

down-regulates quantity by destabilization

0.35

We characterize a new Myc-interacting factor, TRPC4AP (transient receptor potential cation channel, subfamily C, member 4-associated protein)/TRUSS (tumor necrosis factor receptor-associated ubiquitous scaffolding and signaling protein), which is the receptor for a DDB1 (damage-specific DNA-binding protein 1)-CUL4 (Cullin 4) E3 ligase complex for selective Myc degradation through the proteasome. TRPC4AP/TRUSS binds specifically to the Myc C terminus and promotes its ubiquitination and destruction through the recognition of evolutionarily conserved domains in the Myc N terminus.

SIGNOR-271963

Q9UHC7

P11940

1

ubiquitination

up-regulates activity

0.35

We show that MKRN1 directly binds to the cytoplasmic poly(A)-binding protein (PABPC1) and associates with polysomes. MKRN1 is positioned upstream of poly(A) tails in mRNAs in a PABPC1-dependent manner. Ubiquitin remnant profiling and in vitro ubiquitylation assays uncover PABPC1 and ribosomal protein RPS10 as direct ubiquitylation substrates of MKRN1.Our data show that MKRN1 associates with polysomes and ubiquitylates RPS10, indicating a role in translational control. We hypothesize that ribosomes encountering the MKRN1-PABPC1 complex are stalled, possibly via ubiquitylation of RPS10 on K107 and other MKRN1 substrates.

SIGNOR-272215

Q9Y625

Q13635

1

binding

up-regulates activity

0.35

Based on results from in vitro experiments, we had previously proposed that GPC6 stimulates Hh signaling by interacting with Hh and Patched1 (Ptc1), and facilitating/stabilizing their interaction.

SIGNOR-264031

P06241

Q96PD2

1

phosphorylation

up-regulates activity

0.35

Mutagenesis analysis of ESDN's seven intracellular tyrosines in YxxP motifs found several contribute to the binding of ESDN to the SH2 domains of both CrkCT10 regulator of kinase Crk-Like (CrkL) and a representative SFK Fyn. Quantitative mass spectrometry showed that at least three of these (Y565, Y621 and Y750), as well as non-YxxP Y715, are reversibly phosphorylated. SFK activity was shown to be sufficient, but not required for the interaction between ESDN and the CrkL-SH2 domain. Finally, antibody-mediated ESDN clustering induces ESDN tyrosine phosphorylation and CrkL-SH2 binding.

SIGNOR-273946

P67775

P56524

1

dephosphorylation

up-regulates

0.35

Different signal-regulated serine/threonine kinases phosphorylate class ii histone deacetylases (hdacs) to promote nuclear export, cytosolic accumulation, and activation of gene transcriptionhere we show that hdac4 forms a complex with the pp2a holoenzyme c alpha, a alpha, b/pr55 alpha. In vitro and in vivo binding studies demonstrate that the n-terminus of hdac4 interacts with the catalytic subunit of pp2a. Hdac4 is dephosphorylated by pp2a

SIGNOR-159492

O75487

P56704

1

binding

up-regulates

0.35

Gpc4 bound to wnt3a and wnt5a which activate the beta-catenin-dependent and -independent pathways, respectively, and colocalized with wnts on the cell surface. Expression of gpc4 enhanced the wnt3a-dependent beta-catenin pathway and the wnt5a-dependent beta-catenin-independent pathway, and knockdown of gpc4 suppressed both pathways

SIGNOR-195749

P68400

P35659

1

phosphorylation

up-regulates

0.35

Dek is phosphorylated by the protein kinase ck2 in vitro and in vivo on ser32

SIGNOR-125912

Q15418

P50549

1

phosphorylation

up-regulates activity

0.35

Here we describe that the 90-kDa ribosomal S6 kinase 1 (RSK1), a protein kinase downstream of the extracellular signal-regulated kinase (ERK) subclass of MAPKs, binds to ER81, phosphorylates it, and enhances ER81-dependent transcription. Two in vivo RSK1 phosphorylation sites within ER81, Ser(191) and Ser(216), were identified, whose mutation to alanine reduces ER81 activity upon ERK-MAPK stimulation.

SIGNOR-249163

P51608

Q13224

1

transcriptional regulation

down-regulates quantity by repression

0.35

The interaction of MeCP2 with the 2BI3 and 2BI5 sites was strikingly reduced in neurons maintained in the presence of TTX (Fig. 2C). This result is consistent with the classical view of MeCP2 as a general transcriptional repressor, in that the reduced association leads to increased expression of NR2B.

SIGNOR-264685

P05412

O94925

1

transcriptional regulation

up-regulates quantity by expression

0.35

The transcription factor c-Jun can directly bind to the GLS gene promoter and enhance expression

SIGNOR-268035

Q14832

P63092

1

binding

up-regulates activity

0.35

MGluRs are members of the G-protein-coupled receptor (GPCR) superfamily, the most abundant receptor gene family in the human genome. GPCRs are membrane-bound proteins that are activated by extracellular ligands such as light, peptides, and neurotransmitters, and transduce intracellular signals via interactions with G proteins. The resulting change in conformation of the GPCR induced by ligand binding activates the G protein, which is composed of a heterotrimeric complex of α, β, and γ subunits.

SIGNOR-264083

Q86YT6

Q9NYJ7

1

ubiquitination

up-regulates activity

0.35

Mib physically interacts with Delta and promotes its ubiquitination and internalization [66], which have been shown to up-regulate Notch activity.

SIGNOR-209672

Q96J02

Q9UBN4

1

ubiquitination

down-regulates activity

0.35

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-272624

Q13829

P61586

1

binding

down-regulates quantity

0.35

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-264235

P17612

P17752

1

phosphorylation

up-regulates activity

0.35

The activation of tryptophan hydroxylase by protein kinase A is mediated by the phosphorylation of serine-58 within the regulatory domain of the enzyme.

SIGNOR-250062

O14965

Q8TEW0

1

phosphorylation

up-regulates

0.35

Aurora a interacts directly with the atypical protein kinase c binding domain of par3 and phosphorylates it at serine 962. The phosphorylation of par3 at serine 962 contributes to its function in the establishment of neuronal polarity.

SIGNOR-188398

Q13164

Q92886

1

phosphorylation

up-regulates activity

0.35

Activation of ERK5 potentiates while inhibition of ERK5 attenuates Neurog1 stimulated neurogenesis.|ERK5 directly phosphorylated Neurog1 in vitro and modulated the transcriptional and pro-neural activity of Neurog1 in cortical progenitors.

SIGNOR-278364

P51955

Q8N137

1

phosphorylation

down-regulates activity

0.35

The opposite outcomes in NEK2- and centrobin-depleted cells suggest that NEK2 antagonizes biological functions of centrobin.|These results suggest that NEK2 phosphorylates specific sites of centrobin, which are distinct from the PLK1 phosphorylation sites.

SIGNOR-279545

Q96QE3

O60885

1

binding

up-regulates

0.35

ATAD5 Interacts with BRD4 through a Conserved BET Protein-Binding Domain. BRD4-ATAD5 binds to acetyl-histones in nascent chromatin. BRD4 release from chromatin correlates with PCNA unloading. Disruption of the interaction between BRD4 and acetyl-histones or between BRD4 and ATAD5 reduces the PCNA amount on chromatin.

SIGNOR-266412

P06493

Q06830

1

phosphorylation

down-regulates

0.35

Peroxiredoxin (prx) i is a member of the peroxiredoxin family of peroxidases and contains a consensus site (thr(90)-pro-lys-lys) for phosphorylation by cyclin-dependent kinases (cdks). This protein has now been shown to be phosphorylated specifically on thr(90) by several cdks, including cdc2, in vitro. Phosphorylation of prx i on thr(90) reduced the peroxidase activity of this protein by 80%.

SIGNOR-87097

P03956

P02461

1

cleavage

down-regulates quantity by destabilization

0.35

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-272339

P06241

Q9HBA0

1

phosphorylation

up-regulates activity

0.35

ROS could be detected by Fyn, which is required to activate TRPV4 in a redox-sensitive manner.|The Ca 2+ response to H 2 O 2 required the basal phosphorylation of TRPV4 by the Src kinase Fyn, which may serve as the redox sensor responsible for TRPV4 activation (Figure 2 ) [220] , and was able to increase barrier permeability [219] .

SIGNOR-279991

P06493

P11387

1

phosphorylation

up-regulates activity

0.349

In vitro kinase assays demonstrated that Ser(10) can be phosphorylated by casein kinase II, Ser(21) can be phosphorylated by protein kinase Calpha, and Ser(112) and Ser(394) can be phosphorylated by Cdk1.Collectively these results indicate that topo I is phosphorylated during mitosis at multiple sites, one of which enhances DNA relaxation activity in vitro and interaction with DNA in cells.

SIGNOR-276157

P20742

P14780

2

binding

down-regulates activity

0.349

Both PZP and a2M collagenase complexes incubated with gelatin demonstrated a significant inhibition of the catalytic activity| MMP-2 and MMP-9 cause a significant degradation of these bands and the background, a degradation which is prevented by both a2M and PZP.

SIGNOR-261802

P17252

P10415

1

phosphorylation

up-regulates

0.349

Purified pkca can efficiently and directly phosphorylate bcl2 at serine 70

SIGNOR-60120

P48436

P32243

1

binding

up-regulates activity

0.349

BEST1 promoter activity was increased by SOX9 overexpression and decreased by siRNA-mediated SOX9 knockdown. SOX9 physically interacted with MITF and OTX2 and orchestrated synergistic activation of the BEST1 promoter with the paired SOX site playing essential roles.

SIGNOR-255184

P17612

Q14103

1

phosphorylation

up-regulates

0.349

Protein kinase a enhances, whereas glycogen synthase kinase-3 beta inhibits, the activity of the exon 2-encoded transactivator domain of heterogeneous nuclear ribonucleoprotein d in a hierarchical fashion.

SIGNOR-116144

Q969H0

Q96KS0

1

ubiquitination

down-regulates quantity by destabilization

0.349

Mechanistically, we further show that FBW7, an E3 ligase complex component that is frequently downregulated in TNBC, negatively regulates EglN2 protein stability.

SIGNOR-261997

Q16513

O15553

1

phosphorylation

down-regulates activity

0.349

PKNs bind to human pyrin and phosphorylate S208 and S242. Pyrin forms an inflammasome when mutant or in response to bacterial modification of the GTPase RhoA. We found that RhoA activated the serine-threonine kinases PKN1 and PKN2 that bind and phosphorylate pyrin. Phosphorylated pyrin bound to 14-3-3 proteins, regulatory proteins that in turn blocked the pyrin inflammasome.

SIGNOR-275464

P49841

Q7KZI7

1

phosphorylation

down-regulates activity

0.349

MARK family kinases can be activated by phosphorylation of a conserved threonine (Thr-208 in MARK2), and inactivated by phosphorylation of a serine (Ser-212), both in the activation loop of the catalytic domain. Activation is achieved by the kinases MARKK/TAO1 or LKB1, although the inactivating kinase was unknown. We show here that GSK3beta serves the role of the inhibitory kinase.

SIGNOR-276163

Q04759

Q00613

1

phosphorylation

up-regulates

0.349

At the same time, ea causes pkc?-Mediated phosphorylation and activation of the transcription factor heat shock factor 1, an inducer of glucose dependence.

SIGNOR-200576

O14829

O14737

1

dephosphorylation

down-regulates quantity by destabilization

0.349

Here, we report that the serine/threonine phosphatase PPEF-1 interacts with and dephosphorylates PDCD5 at Ser 119, which leads to PDCD5 destabilization.|These results demonstrate that PPEF-1 reduces PDCD5 stability via PDCD5 dephosphorylation.

SIGNOR-277008

O14713

P16144

1

binding

down-regulates activity

0.349

Integrins also bind to many PTBdomain-containing proteins (Calderwood et al., 2003) – including Dok1 and integrincytoplasmic-domain-associated protein 1 (ICAP1) – and these can compete with talin for binding to integrin and so can impair activation

SIGNOR-257658

P14780

P20742

2

cleavage

down-regulates quantity by destabilization

0.349

The complex formation was confirmed by the use of 125I-labeled matrix metalloproteinase-2. The cleavage sites in the "bait" regions following formation of high-molecular-weight complexes of matrix metalloproteinases with the alpha-macroglobulins were determined by protein sequence analysis. Pregnancy zone protein was cleaved at Thr693-Tyr694 and alpha2-macroglobulin at Gly679-Leu680 and Arg696-Leu697 by matrix metalloproteinase-2. Matrix metalloproteinase-9 cleaved alpha2-macroglobulin at the same site as matrix metalloproteinase-2, but cleavage of pregnancy zone protein was at Leu753-Ser754.|MMP-2 and MMP-9 cause a significant degradation of these bands and the background, a degradation which is prevented by both a2M and PZP.

SIGNOR-261785

Q8TCY5

Q01726

1

binding

down-regulates activity

0.349

We report that MRAP and MRAP2 can interact with all 5 MCRs. This interaction results in MC2R surface expression and signaling. In contrast, MRAP and MRAP2 can reduce MC1R, MC3R, MC4R, and MC5R responsiveness to [Nle4,D-Phe7]alpha-melanocyte-stimulating hormone (NDP-MSH). MRAP and MRAP2 can reduce the surface expression of MC4R and also the signaling of this receptor. we observed a significant decrease in the cell-surface expression of MC4R and MC5R in the presence of MRAP and MRAP2. It is interesting that MRAP and MRAP2 have opposite effects in the modulation of different MCR family members.

SIGNOR-252364

Q00987

P46695

1

ubiquitination

down-regulates quantity by destabilization

0.349

FHL2 stimulates MDM2 mediated ubiquitination of IER3 by forming a ternary complex.|Scaffold protein FHL2 facilitates MDM2 mediated degradation of IER3 to regulate proliferation of cervical cancer cells.

SIGNOR-278824

P06239

Q13444

1

phosphorylation

up-regulates

0.349

Hck, and to a lesser extent lck, phosphorylated the adam15. Deletion and point mutation analysis of the adam15 cytoplasmic domain confirmed the importance of the proline-rich motifs for grb2 and lck binding and indicated the regulatory nature of tyr(715) and tyr(735). These data demonstrate selective, phosphorylation-dependent interactions of adam15 with src family ptks and grb2, which highlight the potential for integration of adam functions and cellular signaling.

SIGNOR-112931

P28223

P63096

1

binding

up-regulates activity

0.349

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-256742

O96017

P61289

1

phosphorylation

up-regulates activity

0.349

REGγ interacts with DBC1 and is phosphorylated by Chk2.

SIGNOR-273611

Q5VWQ8

O60674

1

binding

down-regulates activity

0.349

In vascular smooth muscle cells (VSMCs) treated with IFN-γ, DAB2IP directly binds to JAK2 and inhibits its kinase activity, limiting JAK-dependent STAT1/3 and PI3K–AKT phosphorylation and activation

SIGNOR-254760

Q9UM11

O00429

1

ubiquitination

down-regulates quantity

0.349

Here we demonstrate that changes in mitochondrial dynamics as cells exit mitosis are driven in part through ubiquitylation of Drp1 catalyzed by the APC/Ccdh1 (anaphase-promoting complex/cyclosome and its coactivator (Cdh1) E3 ubiquiting ligase complex

SIGNOR-274127

P08172

P09471

1

binding

up-regulates activity

0.349

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-256964

P49137

P53350

1

phosphorylation

up-regulates

0.349

Here, we have identified mk2 as a major plk1 kinase toward ser326, whose phosphorylation is critical to recruit ?-Tubulin to centrosomes and subsequent establishment of functional bipolar spindles. To our knowledge, this is the first direct evidence to demonstrate that the essential function of plk1 in centrosome maturation and bipolar spindle formation is controlled by its upstream kinase.

SIGNOR-179968

Q05086

P78352

1

ubiquitination

down-regulates quantity by destabilization

0.349

E6-induced degradation of DLG4 depends on E6AP in vivo. Our findings as a whole indicate that E6AP is involved in E6-mediated ubiquitination and degradation of DLG4 both in vivo and in vitro.

SIGNOR-271397

Q13315

Q99607

1

phosphorylation

down-regulates activity

0.349

Elf4 is phosphorylated by Atm after gamma irradiation, leading to its degradation.|Thus, Atm promotes Elf4 protein degradation after gamma irradiation via phosphorylation at these sites.

SIGNOR-278466

Q8N1E6

P01106

1

ubiquitination

down-regulates quantity by destabilization

0.349

In this study, we demonstrate that the deubiquitinase USP13 stabilizes c-Myc by antagonizing FBXL14-mediated ubiquitination to maintain GSC self-renewal and tumorigenic potential. USP13 was preferentially expressed in GSCs, and its depletion potently inhibited GSC proliferation and tumor growth by promoting c-Myc ubiquitination and degradation.

SIGNOR-274125

Q7Z5G4

P01112

1

palmitoylation

up-regulates activity

0.349

Covalent lipid modifications mediate the membrane attachment and biological activity of Ras proteins. All Ras isoforms are farnesylated and carboxyl-methylated at the terminal cysteine; H-Ras and N-Ras are further modified by palmitoylation. Here we report that H- and N-Ras are palmitoylated by a human protein palmitoyltransferase encoded by the ZDHHC9 and GCP16 genes. DHHC9 is an integral membrane protein that contains a DHHC cysteine-rich domain. GCP16 encodes a Golgi-localized membrane protein.

SIGNOR-261351

Q13153

P17600

1

phosphorylation

up-regulates activity

0.349

Synapsin I is phosphorylated at Ser603 by p21-activated kinases. the Ser603 residue must be one of the pivotal sites for the release

SIGNOR-250235

Q9H4B4

Q16665

1

phosphorylation

down-regulates

0.348

Polo-like kinase 3 functions as a tumor suppressor and is a negative regulator of hypoxia-inducible factor-1 alpha under hypoxic conditionsplk3 can potentially inhibit hif-1_ by physical interaction and direct phosphorylation

SIGNOR-178743

P19784

Q00613

1

phosphorylation

up-regulates

0.348

Transcriptional activity and dna binding of heat shock factor-1 involve phosphorylation on threonine 142 by ck2.As hsf1 is activated by heat shock simultaneously with the nuclear translocation of the protein kinase ck2, we have investigated the role of ck2 in hsf1 activatio

SIGNOR-99606

P68400

O95863

1

phosphorylation

up-regulates quantity by stabilization

0.348

Serines 11 and 92 participate in the control of snail1 stability and positively regulate snail1 repressive function and its interaction with msin3a corepressor. Furthermore, serines 11 and 92 are required for snail1-mediated emt and cell viability, respectively. Pka and ck2 have been characterized as the main kinases responsible for in vitro snail1 phosphorylation at serine 11 and 92, respectively.

SIGNOR-161771

Q05655

P41594

1

phosphorylation

up-regulates activity

0.348

Thus, we showed that it is phosphorylation of Ser-839, not Thr-840, that is absolutely required for the unique Ca2+ oscillations produced by mGluR5 activation. The Thr-840 residue is important only in that it is permissive for the PKC-dependent phosphorylation of Ser-839.

SIGNOR-249287

Q9UEW8

Q9Y6R1

1

phosphorylation

down-regulates activity

0.348

SPAK phosphorylates the transporters to reduce their surface expression and thus their activity and consequently inhibits ductal secretion to stabilize the resting state. PP1 reverses the effect of SPAK. Molecular analysis revealed that the WNK kinases acted as scaffolds to recruit SPAK, which phosphorylated CFTR and NBCe1-B, reducing their cell surface expression.

SIGNOR-263133

Q96J02

Q16625

1

ubiquitination

down-regulates quantity by destabilization

0.348

Two mechanisms regarding junction protein turnover were illustrated in this process, that is, the Itch-induced occludin ubiquitination and proteasome degradation, and the caveolae-dependent endocytosis of junction proteins (JAM-A, N-cadherin, and \u03b2 -catenin), both of which led to the instability of junction apparatus between adjacent SCs and a subsequent damaged BTB.

SIGNOR-278756

P06493

O15297

1

phosphorylation

down-regulates quantity by destabilization

0.348

Phosphorylation of multiple residues in the catalytic domain of PPM1D during mitosis, including Ser40 by Cyclin-dependent kinase 1 (CDK1), leads to ubiquitination of PPM1D and subsequent proteasomal degradation by Adenomatous polyposis coli (APC) and cell-division cycle protein 20 (CDC20)

SIGNOR-275489

P11309

P30307

1

phosphorylation

up-regulates activity

0.348

First, Pim-1 activates the Cdc25C phosphatase directly through phosphorylation, very probably at the N-terminal part of the protein.|We find that phosphorylation by Pim-1 enhances the phosphatase activity of Cdc25C and in transfected cells that are arrested in G2/M by bleomycin, Pim-1 can enhance progression into G1.

SIGNOR-278298

Q7Z553

Q9NPF5

1

binding

up-regulates quantity by stabilization

0.348

The anti-tumorigenic effect of MDGA2 was mediated through direct stabilising of DNA methyltransferase 1 associated protein 1 (DMAP1), which played a tumour suppressive role in gastric cancer. MDGA2 expression and MG132 treatment increased the level of DMAP1, suggesting that the MDGA2–DMAP1 interaction stabilises DMAP1 by inhibiting its ubiquitin-mediated degradation.

SIGNOR-264240

P60763

Q99828

1

binding

up-regulates activity

0.348

We here report that CIB, a protein that binds to the alpha(IIb)beta(3) fibrinogen receptor, interacts exclusively with activated (V12) Rac3 but not Rac1 or Rac2. Binding of V12Rac3 to CIB was mediated by the C-terminal end of Rac3 and by Rac3 membrane localization

SIGNOR-269060

O43187

Q07955

1

phosphorylation

down-regulates activity

0.348

IRAK2 phosphorylates SRSF1 and thereby reduces SRSF1 binding to the target mRNAs.

SIGNOR-278406

Q02763

P35590

1

phosphorylation

up-regulates activity

0.348

Thus, Tie2 was able to induce Tie1 phosphorylation.|When cotransfected, Tie2 formed heteromeric complexes with Tie1, enhanced Tie1 activation, and induced phosphorylation of a kinase-inactive Tie1 in a ligand-dependent manner.

SIGNOR-279769

P22455

P42224

1

phosphorylation

up-regulates activity

0.348

Activation of Stat1 and Stat3 by FGFR derivatives. Lysates of 293T cells transfected as indicated were analysed by Western blotting using Phospho-Stat1 (Y701) antisera (top) or Stat1 antisera (bottom). (b) The same lysates in (a) were re-examined for phosphorylated Stat3 by Western blotting with Phospho-Stat3 (Y705) (top). all three FGFR family members examined here are able to lead to Stat activation. Expression of the 'TDII-like' derivatives of FGFR1, FGFR3, and FGFR4, as well as myrR1-WT, led to phosphorylation of both Stat1 and Stat3.

SIGNOR-251141

P17252

Q13507

1

phosphorylation

down-regulates

0.348

There are two known phosphorylation-mediated inactivation mechanisms for trpc3 channels. Protein kinase g (pkg) inactivates trpc3 by direct phosphorylation on thr-11 and ser-263 of the trpc3 proteins, and protein kinase c (pkc) inactivates trpc3 by phosphorylation on ser-712.

SIGNOR-130269

P49593

Q16566

1

dephosphorylation

down-regulates activity

0.348

Calmodulin-dependent protein kinase phosphatase (CaMKP) dephosphorylates and concomitantly deactivates multifunctional Ca(2+)/calmodulin-dependent protein kinases , such as CaMKI, CaMKII, and CaMKIV.

SIGNOR-277157

Q96A56

Q9H492

1

binding

up-regulates

0.348

Tp53inp1-lc3 interaction occurs via a functional lc3-interacting region (lir).

SIGNOR-196670

Q9UBF6

P46527

1

ubiquitination

down-regulates activity

0.348

SAG (Sensitive to Apoptosis Gene), also known as RBX2 (RING box protein 2), ROC2 (Regulator of Cullins 2), or RNF7 (RING Finger Protein 7), was originally cloned in our laboratory as a redox inducible antioxidant protein and later characterized as the second member of the RBX/ROC RING component of the SCF (SKP1-CUL-F-box Proteins) E3 ubiquitin ligase. by forming a complex with other components of the SCF E3 ligase, SAG promotes ubiquitination and degradation of a number of protein substrates, including c-JUN, DEPTOR, HIF-1α, IκBα, NF1, NOXA, p27, and procaspase-3, thus regulating various signaling pathways and biological processes.

SIGNOR-271447

P31751

Q9UBK2

1

phosphorylation

down-regulates

0.348

Here we describe a mechanism by which insulin, through the intermediary protein kinase akt2/protein kinase b (pkb)-beta, elicits the phosphorylation and inhibition of the transcriptional coactivator peroxisome proliferator-activated receptor-coactivator 1alpha (pgc-1alpha), a global regulator of hepatic metabolism during fasting / phosphorylation of pgc-1? At ser?570 Is required for akt to inhibit recruitment of pgc-1? To chromatin.

SIGNOR-155536

P49841

P11388

1

phosphorylation

down-regulates quantity by destabilization

0.348

This study also reports the novel finding that topoIIα may be a target of GSK3β phosphorylation. Evidence suggests that CK2 serves as a priming kinase, through phosphorylation at Ser1365, for GSK3β-mediated phosphorylation at Ser1361.

SIGNOR-276301

P50053

P60891

1

phosphorylation

up-regulates activity

0.348

Ketohexokinase-A (KHK-A; also known as fructokinase-A) phosphorylates PRPS1 T225 and activates PRPS1 by blocking the binding of ADP, AMP, and GDP, which is required for hepatocellular carcinoma development

SIGNOR-265735

P00519

Q9Y6Q9

1

phosphorylation

up-regulates

0.348

Tyrosine phosphorylation of the nuclear receptor coactivator aib1/src-3 is enhanced by abl kinase and is required for its activity in cancer cellstyrosine kinase directly phosphorylates aib1/src-3 at y1357 and modulates the association of aib1 with c-abl, eralpha, the transcriptional cofactor p300,

SIGNOR-180571

P20749

O15379

1

binding

up-regulates

0.348

We show that bcl-3 is a substrate for the protein kinase gsk3 and that gsk3-mediated bcl-3 phosphorylation, which is inhibited by akt activation, targets its degradation through the proteasome pathway. This phosphorylation modulates its association with hdac1, 3 and 6.

SIGNOR-129804

P05771

P06730

1

phosphorylation

up-regulates

0.348

Phosphorylation of eIF-4E on serine 209 by protein kinase C is inhibited by the translational repressors, 4E-binding proteins.[..] This suggests a two-step model for the phosphorylation (and activation) of eIF4E by growth factors and hormones: first, dissociation of eIF4E .

SIGNOR-248946

P07900

Q9HC29

1

binding

up-regulates quantity by stabilization

0.348

Nod2 is constitutively associated with a chaperone protein, Hsp90, which is required for Nod2 stability and protects Nod2 from degradation.

SIGNOR-252414

P42574

O75475

1

cleavage

down-regulates

0.348

Ledgf/ p75 has a cooh-terminally truncated splice variant, p52 / during apoptosis, caspase-3 cleaved p52 to generate a p38 fragment that lacked the nh2-terminal pwwp domain and failed to transactivate the hsp27 promoter in reporter assays. However, p38 retained chromatin association properties and repressed the transactivation potential of ledgf/p75

SIGNOR-180144

P43405

Q92918

1

phosphorylation

up-regulates activity

0.348

BCR ligation induced rapid tyrosine-phosphorylation of HPK1 mainly by Syk and Lyn, resulting in its association with BASH and catalytic activation. BCR-mediated activation of HPK1 was impaired in Syk- or BASH-deficient B cells. The functional SH2 domain of BASH and Tyr-379 within HPK1 which we identified as a Syk-phosphorylation site were both necessary for interaction of both proteins and efficient HPK1 activation after BCR stimulation.

SIGNOR-246567

Q9UNH5

P48200

1

dephosphorylation

up-regulates activity

0.348

IRP2 Ser-157 is phosphorylated by Cdk1/cyclin B1 during G(2)/M and is dephosphorylated during mitotic exit by the phosphatase Cdc14A. Ser-157 phosphorylation during G(2)/M reduces IRP2 RNA-binding activity and increases ferritin synthesis, whereas Ser-157 dephosphorylation during mitotic exit restores IRP2 RNA-binding activity and represses ferritin synthesis.

SIGNOR-248829

P12931

P08559

1

phosphorylation

down-regulates activity

0.348

Src inactivated PDH through direct phosphorylation of tyrosine-289 of PDH E1α subunit (PDHA1).

SIGNOR-277204

P46734

Q9Y463

1

phosphorylation

up-regulates

0.348

Mkk3 enhanced mirk kinase activity. Mkk3 possibly activates mirk by phosphorylating it.

SIGNOR-86731

Q9NYY3

P05067

1

phosphorylation

up-regulates activity

0.348

Here we show that Polo-like kinase 2 (Plk2), an activity-inducible regulator of homeostatic plasticity, directly binds and phosphorylates threonine-668 and serine-675 of APP in\u00a0vitro and associates with APP in\u00a0vivo.|Plk2 was necessary and sufficient to induce BACE-1-mediated APP amyloidogenic processing following overexcitation, associated intimately with APP, and directly phosphorylated the APP C-terminus.

SIGNOR-279424

P61586

Q14192

1

relocalization

up-regulates

0.348

Here, we show that stimulation of the rho pathway induces translocation of the transcriptional lim-only coactivator fhl2 to the nucleus and subsequent activation of fhl2- and androgen receptor-dependent genes.

SIGNOR-114071

Q05513

P55211

1

phosphorylation

down-regulates

0.348

Inhibitor sensitivity and interactions with caspase 9 indicate that the predominant kinase that targets ser144 is the atypical protein kinase c isoform zeta (pkczeta).

SIGNOR-141629

P12931

P42681

1

phosphorylation

up-regulates activity

0.348

We further demonstrate that Rlk can be phosphorylated and activated by Src kinases, leading to a decrease in its half-life. A specific tyrosine in the activation loop of Rlk, Y420, is required for phosphorylation and activation, as well as for decreased stability, but is not required for lipid RAFT association.

SIGNOR-247346

P68400

P27348

1

phosphorylation

down-regulates activity

0.347

The neuroprotective effect of 14-3-3theta against rotenone toxicity is dependent on the inhibition of the pro-apoptotic factor Bax|Phosphorylation at S232 induced by rotenone is reduced by casein kinase inhibitors, and is not dependent on alphasyn.| The S232D mutant partially reduced the ability of 14-3-3theta to inhibit Bax activation in response to rotenone. Based on these findings, we propose that phosphorylation of 14-3-3s at serine 232 contributes to the neurodegenerative process in PD.

SIGNOR-264405

Q9HC98

O95235

1

phosphorylation

down-regulates activity

0.347

We show that Nek9, Nek6, and the kinesin Mklp2 form a signaling module, which is required for Mklp2 to localize to the central spindle in anaphase. Nek6 also phosphorylates Mklp2 at Ser244, inhibiting its bundling activity until anaphase onset.

SIGNOR-273891

Q9Y6Y8

Q15437

1

binding

up-regulates activity

0.347

The results showed that the N-terminal region of p125 is important for the interaction with Sec23p. We confirmed the interaction between the two proteins by a yeast two-hybrid assay. Overexpression of p125, like that of mammalian Sec23p, caused disorganization of the endoplasmic reticulum-Golgi intermediate compartment and Golgi apparatus, suggesting its role in the early secretory pathway.

SIGNOR-265306

P36508

P17987

1

transcriptional regulation

up-regulates quantity by expression

0.347

The transcription from the minimalCcta promoter was up-regulated 3-fold by ZNF143 and 6-fold by ZNF76 when full-length proteins were co-expressed, indicating that both ZNF143 and ZNF76 can enhance Ccta transcription.

SIGNOR-266221

Q92793

P48551

1

acetylation

up-regulates activity

0.347

By binding to IFNalphaR2 within the region where two adjacent proline boxes bear phospho-Ser364 and phospho-Ser384, CBP acetylates IFNalphaR2 on Lys399, which in turn serves as the docking site for interferon regulatory factor 9 (IRF9)RF9 interacts with the acetyl-Lys399 motif by means of its IRF homology2 (IH2) domain, leading to formation of the ISGF3 complex that includes IRF9, STAT1, and STAT2.

SIGNOR-217783

P11362

Q15118

1

phosphorylation

up-regulates

0.347

Mitochondrial pdhk1 is tyrosine phosphorylated and activated by fgfr1 in cancer cells further mass spectrometric analysis identified three tyrosine residues of pdhk1, including y136, y243 and y244, that are phosphorylated by fgfr1

SIGNOR-193454

P49759

P18031

1

phosphorylation

up-regulates activity

0.347

The CLK family kinases, CLK1 and CLK2, phosphorylate and activate the tyrosine phosphatase, PTP-1B. | although CLK1 and CLK2 directly phosphorylate PTP-1B on both Ser50 and Ser242/Ser243, the preferred CLK phosphorylation site is Ser50, as it is preferentially phosphorylated at an approximate ratio of 9:1 over the Ser242/Ser243 site.

SIGNOR-250773

Q9UQM7

Q86UR5

1

phosphorylation

up-regulates

0.347

Two serine residues in rim1 (ser-241 and ser-287) and one serine residue in rim2 (ser-335) were required for 14-3-3 binding. Incubation with ca2+/calmodulin-dependent protein kinase ii greatly stimulated the interaction of recombinant n-terminal rim but not the s241/287a mutant with 14-3-3,

SIGNOR-103890

P05981

P08709

1

cleavage

up-regulates activity

0.347

Hepsin, a putative membrane-associated serine protease, activates human factor VII and initiates a pathway of blood coagulation on the cell surface leading to thrombin formation|In contrast, an activation cleavage site factor VII mutant, R152E factor VII, was not cleaved by hepsin-transfected cells, suggesting that factor VII and S344A factor VII were activated on these cells by cleavage of the Arg152-Ile153 peptide bond. I

SIGNOR-263638