GleghornLab/Signor_3class · Datasets at Hugging Face

IdA stringlengths 6 21	IdB stringlengths 6 21	labels int64 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
P50148	Q92847	2	binding	up-regulates activity	0.474	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-257380
P00519	Q9UPY6	1	phosphorylation	up-regulates activity	0.582	WAVE3-Abl interaction promotes the tyrosine phosphorylation of WAVE3 by Abl, and STI-571, a specific inhibitor of Abl kinase activity, abrogates the Abl-mediated phosphorylation of WAVE3.	SIGNOR-259077
P98170	Q9NR28	2	ubiquitination	down-regulates quantity by destabilization	0.914	Xiap functions as ubiquitin ligase toward smac to inhibit apoptosis.	SIGNOR-134504
Q9BRV8	Q9UHD2	0	phosphorylation	down-regulates quantity	0.718	Mechanism of endogenous regulation of the type I interferon response by suppressor of I\u03baB kinase epsilon (SIKE), a novel substrate of TANK-binding kinase 1 (TBK1).\|TBK1 phosphorylation of IRF3 and SIKE displayed negative cooperativity.	SIGNOR-280152
Q8NFZ4	Q9P2S2	2	binding	up-regulates activity	0.829	Pre- and postsynaptic plasma membranes are always precisely aligned, and are separated by a synaptic cleft of ~20 nm. The cleft contains an undefined proteinaceous material in the middle, and is presumably bridged by synaptic cell-adhesion molecules such as Nrxns and Nlgns that align the pre- and postsynaptic elements and mediate trans-synaptic signaling.\|Nlgns bind to both alpha- and beta-Nrxns with nanomolar affinities; binding involves the sixth LNS-domain of alpha-Nrxns which corresponds to the only LNS-domain of beta-Nrxns52. The binding affinities differ characteristically between various pairs of Nlgns and Nrxns, and are controlled by alternative splicing of both Nrxns and Nlgns (Figure 1c)	SIGNOR-264156
P98177	P16220	2	binding	down-regulates activity	0.308	We provide evidence that the acetyltransferase creb-binding protein (cbp) binds foxo resulting in acetylation of foxo. This acetylation inhibits foxo transcriptional activity	SIGNOR-124711
O14920	P35813	0	dephosphorylation	down-regulates	0.308	Using a functional genomic approach, we have identified two protein serine/threonine phosphatases, ppm1a and ppm1b, as ikkbeta phosphatases. Overexpression of ppm1a or ppm1b results in dephosphorylation of ikkbeta at ser177 and ser181 and termination of ikkbeta-induced nf-kappab activation	SIGNOR-181659
P36956	P49327	1	transcriptional regulation	up-regulates quantity by expression	0.495	Ultimately, both the AKT and MAPK transduction pathways regulate FASN expression through the modulation of expression of sterol regulatory element-binding protein (SREBP)-1c, which binds to regulatory elements in the FASN promoter. Proto-oncogene FBI-1 (Pokemon), a transcription factor of the bric--brac tramtrack broad complex/pox viruses and zinc fingers (BTB/POZ) domain family, interacts directly with SREBP-1c through its DNA-binding domain to synergistically activate the transcription of FASN	SIGNOR-242884
Q9NZP8	P00738	1	cleavage	up-regulates activity	0.375	We demonstrate that coexpression of the proform of Hp (proHp) and C1r-LP in COS-1 cells effected cleavage of proHp in the endoplasmic reticulum. This cleavage depended on proteolytic activity of C1r-LP because mutation of the putative active-site Ser residue abolished the reaction. Furthermore, incubation of affinity-purified C1r-LP and proHp led to the cleavage of the latter protein. ProHp appeared to be cleaved at the expected site because substitution of Gly for Arg-161 blocked the reaction.	SIGNOR-256358
P31749	P84243	1	phosphorylation	down-regulates activity	0.2	Additionally, active akt1 kinase strongly phosphorylates histone h3 at serine 10 in vitro	SIGNOR-98285
O14793	Q13705	2	binding	up-regulates activity	0.642	The purified C-terminal myostatin dimer was capable of binding the activin type II receptors, Act RIIB and, to a lesser extent, Act RIIA	SIGNOR-235153
P04637	P45984	0	phosphorylation	up-regulates	0.747	These findings strongly suggest that jnks are the major direct signaling mediators of uvb-induced p53 phosphorylation at serine 20. furthermore, phosphorylation of p53 at serine 20 by uvb-activated jnks and uvb-induced p53-dependent transcriptional activity were suppressed in jnk1 or jnk2 knockout (jnk1(-/-) or jnk2(-/-)) cells.	SIGNOR-115835
Q07820	P49840	0	phosphorylation	down-regulates quantity by destabilization	0.457	MCL-1 was phosphorylated by GSK-3 at a conserved GSK-3 phosphorylation site (S159). Glycogen Synthase Kinase-3 Regulates Mitochondrial Outer Membrane Permeabilization and Apoptosis by Destabilization of MCL-1. threonine 163, which represents the GSK-3 priming phosphorylation in this protein	SIGNOR-251217
P00533	O43639	2	binding	up-regulates	0.399	Growth factor binding to receptor protein tyrosine kinases (r-ptks)1 induces their dimerization and trans-phosphorylation, creating docking sites for proteins containing sh2 and ptb protein interaction domains. Nck binds to the pdgf and egfr receptors (figure 3c).	SIGNOR-64731
Q05655	Q96C90	1	phosphorylation	up-regulates activity	0.2	Recombinant tagged PHI-1 was phosphorylated by protein kinase C at two sites, one a Ser and one a Thr; phosphorylation enhanced inhibitory potency 50-fold.	SIGNOR-265739
Q9BVG3	Q9H257	1	ubiquitination	up-regulates activity	0.51	Importantly, using in vitro ubiquitination assays with purified proteins, we verified that CARD9 is directly ubiquitinated by TRIM62 at residue K125; this ubiquitination is dependent on the ligase activity of TRIM62 and does not occur in CARD9 Delta11 (XREF_FIG).	SIGNOR-278552
Q14332	P41221	2	binding	down-regulates	0.766	Fz2 was also required for the wnt3a-dependent accumulation of beta-catenin, and wnt5a competed with wnt3a for binding to fz2 in vitro and in intact cells, thereby inhibiting the beta-catenin pathway.	SIGNOR-23441
Q99959	P15924	2	binding	up-regulates quantity by stabilization	0.787	In contrast to the proper membrane localization of PKP2 and DSP after cotransfection of both WT proteins, mutant PKP2 C796R protein was not able to interact with FLAG-DSP to enable assembly at the junctional plaque, indicating the requirement of functional PKP2 for DSP integration into the desmosome.	SIGNOR-261254
P03951	P01008	0	cleavage	down-regulates activity	0.657	Antithrombin (AT), a member of the serine protease inhibitor (SERPIN) superfamily, is a major circulating inhibitor of blood coagulation proteases such as factor (F) IIa (known as thrombin), FXa and, to a lesser extent, FIXa, FXIa and FXIIa. SERPINC1, which encodes AT in humans, is located on chromosome 1q25.1	SIGNOR-264137
O00418	P23443	0	phosphorylation	down-regulates activity	0.736	We show that two such kinases, p70 s6 kinase (regulated via mtor) and p90(rsk1) (activated by erk), phosphorylate eef2k at a conserved serine and inhibit its activity	SIGNOR-109712
P60484	P53350	0	phosphorylation	down-regulates activity	0.534	Subsequently, Plk1 phosphorylation of PTEN was shown to be responsible for its inactivation.	SIGNOR-280070
P04637	Q13131	0	phosphorylation	up-regulates	0.48	Ampk activation induces phosphorylation of p53 on serine 15, and this phosphorylation is required to initiate ampk-dependent cell-cycle arrest	SIGNOR-135960
P08243	P08047	0	transcriptional regulation	up-regulates quantity by expression	0.2	Sp1 and Sp3 Activate Transcription Driven by the AS Promoter	SIGNOR-268019
P33076	P48382	2	binding	up-regulates activity	0.759	RFX5 can activate transcription only in cooperation with CIITA. RFX5 and CIITA associate to form a complex capable of activating transcription from class II major histocompatibility complex promoters. In this complex, promoter specificity is determined by the DNA binding domain of RFX5 and the general transcription apparatus is recruited by the acidic activation domain of CIITA.	SIGNOR-240980
P36896	Q15796	1	phosphorylation	up-regulates activity	0.802	ActRIIB, and then partners with a type I receptor, either activin receptor-like kinase 4 (ALK4 or ActRIB) or ALK5 (T²RI), to induce phosphorylation of Smad2/Smad3 and activate a TGF-²-like signaling pathway	SIGNOR-235157
P63244	Q9P126	2	binding	down-regulates quantity by destabilization	0.2	In this study, we reported that RACK1, the receptor for activated C-kinase 1, associated with the cytoplasmic tail of CLEC-2. Moreover, overexpression of RACK1 decreased the stability of CLEC-2 through promoting its ubiquitin-proteasome degradation, without impairing surface expression and downstream signaling of CLEC-2. Taken together, these results suggest RACK1 as a novel modulator of CLEC-2 expression.Previous reports indicated that RACK1 mediated ubiquitin–proteasome degradation of HIF-1a and BimEL by recruiting Elongin-C/B ubiquitin ligase complex	SIGNOR-272781
P10644	Q5VU43	2	binding	up-regulates	0.315	Mmgl acts as a dual-specific akap by anchoring pka regulatory isoforms r1a and r2a.	SIGNOR-173769
P11831	P54821	2	binding	up-regulates	0.442	The human homeodomain proteinphox1interacts functionally with serum response factor (srf) to impart serum responsive transcriptional activity to srf-binding sites in a hela cell cotransfection assay.	SIGNOR-52657
P31749	P14598	1	phosphorylation	up-regulates	0.559	Akt phosphorylates p47phox and mediates respiratory burst activity in human neutrophils. A direct interaction between p47(phox) and akt was shown. Active recombinant akt phosphorylated recombinant p47(phox) in vitro. Mutation analysis indicated that 2 aa residues, ser(304) and ser(328), were phosphorylated by akt. Inhibition of akt activity also inhibited fmlp-stimulated neutrophil chemotaxis.	SIGNOR-252586
Q06187	P50148	2	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
O43516	O00401	2	binding	up-regulates activity	0.933	Recruitment of N-WASP to vaccinia is mediated by WASP-interacting protein (WIP), whereas in Shigella WIP is recruited by N-WASP. Our observations show that vaccinia and Shigella activate the Arp2/3 complex to achieve actin-based motility, by mimicking either the SH2/SH3-containing adaptor or Cdc42 signalling pathways to recruit the N-WASP-WIP complex.	SIGNOR-261880
P35222	P31749	0	phosphorylation	up-regulates	0.805	Phosphorylation of beta-catenin by akt promotes beta-catenin transcriptional activity\|we have demonstrated that akt phosphorylates beta-catenin at ser552 in vitro and in vivo.	SIGNOR-252499
Q96PH1	P17252	0	phosphorylation	up-regulates	0.2	A constitutively active form of pkc? Robustly increased basal and pma-stimulated nox5 activity and promoted the phosphorylation of nox5 on ser490, thr494, and ser498.	SIGNOR-204550
Q13002	P17612	0	phosphorylation	up-regulates activity	0.2	GluR6 glutamate receptor, transiently expressed in mammalian cells, is directly phosphorylated by PKA, and that intracellularly applied PKA increases the amplitude of the glutamate response. Site-specific mutagenesis of the serine residue (Ser 684) representing a PKA consensus site completely eliminates PKA-mediated phosphorylation of this site as well as the potentiation of the glutamate response.	SIGNOR-250315
Q16539	P78536	1	phosphorylation	up-regulates activity	0.405	We show that p38 MAP kinase, which is activated in response to inflammatory or stress signals, directly activates TACE, a membrane-associated metalloprotease that is also known as ADAM17 and effects shedding in response to growth factors and Erk MAP kinase activation. p38alpha MAP kinase interacts with the cytoplasmic domain of TACE and phosphorylates it on Thr(735), which is required for TACE-mediated ectodomain shedding	SIGNOR-163970
Q13105	Q7Z6Z7	0	ubiquitination	down-regulates quantity by destabilization	0.327	Previously, we reported that K48 linked polyubiquitination of Miz1 by Mule triggers its proteasomal degradation, thereby relieving Miz1 suppression on TNF induced JNK activation and apoptosis.	SIGNOR-278697
P35813	P50750	1	dephosphorylation	down-regulates activity	0.493	Taken together, our data indicate that PPM1A and to some extent PPM1B are important negative regulators of P-TEFb function	SIGNOR-248490
P42702	P26441	2	binding	up-regulates	0.742	Ciliary neurotrophic factor (cntf) is a cytokine supporting the differentiation and survival of various cell types in the peripheral and central nervous systems. Its receptor complex consists of a non-signaling alpha chain, cntfr, and two signaling beta chains, gp130 and the leukemia inhibitory factor receptor (lifr)	SIGNOR-81382
P55273	P24941	0	phosphorylation	up-regulates	0.526	Cdk2 and pka were found to participate in p19ink4d phosphorylation process and that they would mediate serine 76 and threonine 141 modifications respectively. Nuclear translocation of p19ink4d induced by dna damage was shown to be dependent on serine 76 phosphorylation.	SIGNOR-197270
O95155	Q99689	1	polyubiquitination	up-regulates activity	0.391	E4B mediated the polyubiquitylation of FEZ1 but did not affect its intracellular stability, suggesting that such modification of FEZ1 is not a signal for its proteolysis. Polyubiquitylation of FEZ1 by E4B required Lys(27) of ubiquitin. Expression of a dominant-negative mutant of E4B in rat pheochromocytoma PC12 cells resulted in inhibition of neurite extension induced either by nerve growth factor or by coexpression of FEZ1 and constitutively active PKCzeta. These findings indicate that E4B serves as a ubiquitin ligase for FEZ1 and thereby regulates its function but not its degradation. The polyubiquitin chain attached by E4B to FEZ1 might therefore facilitate the interaction of FEZ1 with an unidentified target that functions in neuritogenesis.	SIGNOR-271510
O14920	Q92574	1	phosphorylation	down-regulates	0.642	Here we show that ikkbeta, a major downstream kinase in the tnfalpha signaling pathway, physically interacts with and phosphorylates tsc1 at ser487 and ser511, resulting in suppression of tsc1phosphorylation of tsc2 (by akt and erk;refs. 28, 29) and tsc1(by ikkbeta;ref. 30) results in the disruption of the tsc1/2 complex, and thereby activates the oncogenic mtor signaling contributing to tumor progression.	SIGNOR-157296
Q92585	P62805	1	acetylation	down-regulates activity	0.2	We speculated that maml1, in addition to recruiting p300, might directly interact with histones to facilitate histone acetylation. We had observed acetylation of the histones h3 and h4.	SIGNOR-153041
Q9UDY2	Q9GZV5	2	binding	down-regulates	0.507	In addition, yap and taz interact with another tight junction protein zo-2, which was reported to increase nuclear localization of yap and tight-junction localization of taz.	SIGNOR-175931
Q00987	P49137	0	phosphorylation	up-regulates quantity by stabilization	0.364	Hdm2 phosphorylation by mapkap kinase 2 enhances hdm2 activity and promote the degradation of p53.	SIGNOR-133560
P84243	P83916	2	binding	up-regulates activity	0.2	A core characteristic of heterochromatin is its association with heterochromatin protein 1 (HP1) proteins, a highly conserved family of chromosomal proteins that bind to di- and trimethylated H3K9 via a conserved N-terminal domain called the chromodomain (CD) HP1 proteins are a highly conserved family of eukaryotic proteins that bind to methylated histone H3 lysine 9 (H3K9) and are required for heterochromatic gene silencing.	SIGNOR-264491
Q86UR5	A6NNM3	2	binding	down-regulates activity	0.345	SH3 domains of RBPs interact with RIMs. The enhancement of depolarization-induced secretion in PC12 cells by fusion proteins that suppress the associations of RBPs with RIMs and α1 suggests that RBPs may repress RIMs, either directly or through associated proteins.	SIGNOR-264364
P17612	O96004	1	phosphorylation	down-regulates activity	0.296	In vitro and in vivo phosphorylation studies show that both PKA and PKC can phosphorylate HAND1 and -2. T107; S109 within helix I and S98 within the basic domain, are the phosphorylated residues. We determined that modification of HAND1 at residues 107 and 109 affects dimerization affinities with E-proteins, thus changing the bHLH dimer equilibrium within the cell. These modifications also affect HAND1 function.	SIGNOR-249991
Q07812	O15297	0	dephosphorylation	down-regulates activity	0.2	34 In this study, a novel function of Wip1 was identified, that is, its ability to dephosphorylate directly and thus inactivate apoptotic BAX protein in response to gamma irradiation.\|To ascertain whether Wip1 dephosphorylates BAX, recombinant Wip1 was incubated with previously reported BAX-derived phosphopeptides containing Ser87, Ser163, Thr167, and Ser184 in an in vitro phosphatase assay. xref , xref Peptides containing phospho-Thr180 from p38 MAPK and phospho-Thr31 from UNG2 were used as a positive and negative control, respectively. xref As shown in xref , purified Wip1 did not dephosphorylate the four BAX-derived phosphopeptides.	SIGNOR-276993
Q9UJU2	P19883	1	transcriptional regulation	up-regulates quantity by expression	0.28	We further demonstrate that Fst is a direct target of the WNT/β-catenin pathway. Activation and inactivation of β-catenin induced and inhibited Fst expression, respectively, in both C2C12 cells and mouse embryos. Specific TCF/LEF1 binding sites within the promoter and intron 1 region of the Fst gene were required for RSPO2 and WNT/β-catenin-induced Fst expression.	SIGNOR-251722
P04626	Q05209	0	dephosphorylation	down-regulates activity	0.619	In MDA-MB-231 cells, a human triple negative breast cancer cell line, phosphorylation of PTPN12 on Ser 19 was increased in response to cyclin dependent kinase 2 (CDK2), and this impaired PTPN12 's ability to dephosphorylate HER2 on Y1196.\|PTPN12 negatively regulates Her2, by dephosphorylation on Tyr 1196 on Her2.	SIGNOR-277038
Q13114	P29350	0	dephosphorylation	down-regulates activity	0.2	We identified a direct interaction between SHP‐1 and TRAF3; the association between these two proteins resulted in diminished recruitment of CK1ε to TRAF3 and inhibited its K63‐linked ubiquitination; SHP‐1 inhibited K63‐linked ubiquitination of TRAF3 by promoting dephosphorylation at Tyr116 and Tyr446.	SIGNOR-277527
Q8NFG4	Q9HB90	1	gtpase-activating protein	up-regulates activity	0.695	The folliculin tumor suppressor is a GAP for the RagC/D GTPases that signal amino acid levels to mTORC1 [..} RagC/D is a key regulator of the interaction of mTORC1 with the Rag heterodimer and that, unexpectedly, RagC/D must be GDP-bound for the interaction to occur	SIGNOR-256503
P17612	O14921	1	phosphorylation	up-regulates quantity by stabilization	0.334	Phosphorylation of RGS13 by the cyclic AMP-dependent protein kinase inhibits RGS13 degradation.we show that PKA activation also leads to increased steady-state RGS13 expression through RGS13 phosphorylation, which inhibits RGS13 protein degradation. RGS13 phosphorylation was diminished by mutation of an N-terminal Thr residue (T41) identified as a phosphorylation site by mass spectrometry.	SIGNOR-259835
Q01892	P19784	0	phosphorylation	down-regulates quantity by destabilization	0.307	Phosphorylation of the Spi-B transcription factor reduces its intrinsic stability. \| Serine residues 37 in the transactivation domain and 129, 144 and 146 in the PEST domain of Spi-B are phosphorylated by CKII in vitro \| The CKII phosphorylation sites mapped in vitro are phosphorylated in vivo	SIGNOR-251042
Q08211	Q99836	2	binding	up-regulates activity	0.491	We further showed that both DHX9 and DHX36 are localized within the cytosol and are directly bound to the Toll-interleukin receptor domain of MyD88 via their helicase-associated domain 2 and DUF domains. This study demonstrates that DHX9/DHX36 represent the MyD88-dependent DNA sensors in the cytosol of pDCs and suggests a much broader role for DHX helicases in viral sensing.	SIGNOR-260955
P52333	P08575	0	dephosphorylation	down-regulates activity	0.456	CD45 is a JAK phosphatase and negatively regulates cytokine receptor signalling	SIGNOR-248359
Q96KS0	P17252	0	phosphorylation	down-regulates	0.364	Thus, recombinant phd1 was examined for in vitro phosphorylation using protein kinase a, protein kinase calpha, casein kinase i and ii and erk2. The protein was most strongly phosphorylated by protein kinase calpha, and the phosphorylation sites were found to be ser-132, ser-226 and ser-234.Mutation Of ser-132 or ser-234 to asp or glu diminished the enzymatic activity to 25-60%, while mutation of ser-226 scarcely influenced the activity.	SIGNOR-180203
Q7Z434	Q14258	0	polyubiquitination	down-regulates quantity by destabilization	0.77	We report here that RLR activation triggers MAVS ubiquitination on lysine 7 and 10 by the E3 ubiquitin ligase TRIM25 and marks it for proteasomal degradation concomitantly with downstream signaling.	SIGNOR-272042
P42680	Q06187	2	phosphorylation	down-regulates activity	0.496	Tec family protein tyrosine kinases (TFKs) play a central role in hematopoietic cellular signaling. Initial activation takes place through specific tyrosine phosphorylation situated in the activation loop. Further activation occurs within the SH3 domain via a transphosphorylation mechanism, which for Bruton's tyrosine kinase (Btk) affects tyrosine 223.\|In Btk, the SH3 domain mutation Y223F results in enhanced fibroblast transformation, implying that the SH3 domain may play a negative regulatory role	SIGNOR-246652
Q9ULJ6	P10275	2	binding	up-regulates activity	0.709	Our results demonstrate that hZimp10 is a novel AR interacting protein that augments AR-mediated transcription. Moreover, hZimp10 co-localized with AR and SUMO-1 at replication foci throughout S phase, and it was capable of enhancing sumoylation of AR in vivo.	SIGNOR-263935
P07197	Q9HCK8	0	transcriptional regulation	down-regulates quantity	0.2	Many of the most significantly up-regulated genes in Chd8+/− and Chd8−/− NPCs are involved in later stages of neuronal development, including Ascl1 [a central driver of neural reprogramming (29)], Dcx, Map2, Nefm, Neurod4, and Neurog1 (Fig. 2 E and F). Additionally, we found that Sox3 is derepressed in both Chd8+/− and Chd8−/− NPCs, and several other Sox TF members (Sox2, Sox7, and Sox11) became derepressed in the Chd8−/− cells	SIGNOR-268917
O95150	Q93038	2	binding	up-regulates	0.776	The ligand of dr3 is tl1a	SIGNOR-103078
O75914	Q05682	1	phosphorylation	down-regulates	0.2	We investigated the effects of phosphorylation by p(21)-activated kinase 3 (pak) and calmodulin on the 22 kda c-terminal fragment of caldesmon (cad22). We substituted the major pak sites, ser-672 and ser-702, with either alanine or aspartic acid to mimic nonphosphorylated and constitutively phosphorylated states of caldesmon, respectively. Phosphorylation at these sites weakened ca(2+)-calmodulin binding further and reduced the inhibitory activity of cad22 in the absence of ca(2+)-calmodulin.	SIGNOR-167976
P49683	Q14344	2	binding	up-regulates activity	0.264	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-257280
O60260	Q13002	1	ubiquitination	down-regulates quantity by destabilization	0.2	Parkin interacts with and ubiquitinates the GluK2 KAR subunit and regulates GluK2 levels and KAR currents.\|The loss of parkin function increases surface and total GluK2 levels, and consistently increases KAR currents.	SIGNOR-278541
P10912	P43378	0	dephosphorylation	down-regulates activity	0.314	Protein tyrosine phosphatases (PTPs) play key roles in switching off tyrosine phosphorylation cascades, such as initiated by cytokine receptors. We have used substrate-trapping mutants of a large set of PTPs to identify members of the PTP family that have substrate specificity for the phosphorylated human GH receptor (GHR) intracellular domain. Among 31 PTPs tested, T cell (TC)-PTP, PTP-beta, PTP1B, stomach cancer-associated PTP 1 (SAP-1), Pyst-2, Meg-2, and PTP-H1 showed specificity for phosphorylated GHR	SIGNOR-248505
Q12888	Q9Y468	2	binding	down-regulates activity	0.404	L3MBTL1, a tumor suppressor with high affinity for H4K20me2, can block 53BP1 binding at DSBs	SIGNOR-262059
P53350	P47736	1	phosphorylation	down-regulates	0.452	Plk1 phosphorylates ser525 in conserved 524dsghvs529 degron of rap1gap and promotes its interaction with _-trcp. Together, these results further support a model in which plk1, but not cdk1 or gsk-3_-mediated phosphorylation of rap1gap is a prerequisite for mitotic degradation.	SIGNOR-205577
Q7L5N7	P49137	0	phosphorylation	up-regulates activity	0.2	Mass spectrometry and mutagenesis analyses identified Ser34 of LPCAT2 as the phosphorylation site to enhance the catalytic activities. The experiments using inhibitors and siRNA against MAPK cascades demonstrated that LPCAT2 phosphorylation through LPS-TLR4 signaling may directly depend on MAPK-activated protein kinase 2 (MAPKAP kinase 2 or MK2).	SIGNOR-263077
P68400	P30622	1	phosphorylation	up-regulates	0.293	Herein, we have identified polo-like kinase 1 (plk1) and casein kinase 2 (ck2) as two kinases of clip-170 and mapped s195 and s1318 as their respective phosphorylation sites.Plk1- and ck2-associated phosphorylations of clip-170 are involved in the timely formation of kinetochore-microtubule attachments in mitosis	SIGNOR-167168
Q9P286	Q9P286	2	phosphorylation	up-regulates activity	0.2	Active form of Cdc42, but not Rac1 and Rho, protein was able to activate the purified GST-Pak5 autophosphorylation and kinase activity. Mutations of Pak5, which disrupted the interaction of Cdc42 and Pak5, also abolished the induction of autophosphorylation. The H19L/H22L mutant of Pak5 was insensitive to the Cdc42-induced autophosphorylation.	SIGNOR-250248
O95967	P28300	2	binding	up-regulates activity	0.561	Fibulin-4 directly binds LOX, and this interaction enhances fibulin-4 binding to tropoelastin, thus forming a ternary complex that may be critical for elastin cross-linking.	SIGNOR-252135
O00253	P41968	2	binding	down-regulates activity	0.592	AGRP is a potent antagonist of the melanocortin-3 receptor and the MC4R and has also been shown to have a lesser degree of inhibitory action at the melanocortin-5 receptor.	SIGNOR-252380
P68400	Q2V2M9	1	phosphorylation	down-regulates	0.309	We have identified a novel striated muscle-specific splice variant of the formin fhod3 that introduces a casein kinase 2 (ck2) phosphorylation site. The specific targeting of muscle fhod3 to the myofibrils in cardiomyocytes is abolished in phosphomutants or by the inhibition of ck2. Phosphorylation of muscle fhod3 also prevents its interaction with p62/sequestosome 1 and its recruitment to autophagosomes.	SIGNOR-170525
P62136	P28482	1	dephosphorylation	down-regulates	0.446	P-erk1/2 proteins were efficiently dephosphorylated in vitro by protein phosphatases 1 and 2a (pp1/2a) and mapk phosphatase 3 (mkp3)	SIGNOR-103152
P62714	P01106	1	dephosphorylation	down-regulates	0.276	Phosphorylation at ser-62 by pro-directed kinases (p-k) is a prerequisite for gsk3-dependent phosphorylation of thr-58. This triggers binding of pin1, subsequently protein phosphatase 2a (pp2a)-dependent dephosphorylation of ser-62, and then recruitment of scf-fbw7 to the thr-58-phosphorylated myc. Scf-fbw7 polyubiquitinylates myc (branching through lys-48), leading to its proteasomal degradation.	SIGNOR-149726
Q99814	P27361	0	phosphorylation	up-regulates quantity by stabilization	0.26	The activation of ERK1/2 upon hypoxia promoted HIF-2alpha phosphorylation, enhancing its interaction with USP33.Here, we identified USP33 as essential deubiquitinase that stabilizes HIF-2alpha protein in an ERK1/2-dependent manner to promote hypoxia response in cancer cells.	SIGNOR-277584
P18031	O15344	0	ubiquitination	down-regulates quantity	0.2	Proteasome inhibitor treatment diminished the decrease of PTP1B (Figure 5F) caused by TRIM18 overexpression.\|TRIM18 Interacts With PTP1B and Promotes PTP1B Ubiquitination.	SIGNOR-278703
Q96EB6	Q96EP1	0	ubiquitination	down-regulates quantity	0.372	CHFR binds to and ubiquitylates SIRT1, leading to its proteasomal degradation.\|CHFR ubiquitylates and promotes the proteasomal degradation of SIRT1.	SIGNOR-278691
O43542	Q13535	0	phosphorylation	up-regulates activity	0.464	HXRCC3 S225 phosphorylation is mediated by ATR via an ATM-dependent signaling pathway. These data clearly indicate that ATR mediates the late activation of XRCC3 following DSB accumulation.	SIGNOR-262666
Q08828	P04899	2	binding	down-regulates activity	0.597	Adenylate cyclase is regulated by stimulatory hormones through Gs(alpha s beta gamma) and inhibitory hormones through Gi(alpha i beta gamma)	SIGNOR-256499
Q9P2B4	O43815	2	binding	up-regulates activity	0.645	Although CTTNBP2 and CTTNBP2NL are different in terms of tissue and subcellular distribution, our data indicate that, similar to CTTNBP2NL, CTTNBP2 associates with members of the striatin family, namely striatin and zinedin. Moreover, CTTNBP2 is critical for the distribution of striatin and zinedin in dendritic spines. The role of CTTNBP2 in the regulation of the synaptic distribution of striatin and zinedin suggests that CTTNBP2 regulates synaptic signaling through PP2A.	SIGNOR-261702
P68400	P30291	1	phosphorylation	down-regulates quantity by destabilization	0.408	In the present study, we show that phosphorylation of S123 (pS123) by CDK promoted the binding of Wee1A to beta-TrCP through three independent mechanisms. S123 phosphorylation creates a PBD-binding motif and accelerates S53 phosphorylation by Plk1.	SIGNOR-276038
P17612	Q86UR1	1	phosphorylation	down-regulates	0.324	We identified ser-282 as target of mapk and ser-172 as target of pkc and pka in vitro and in a transfected human embryonic kidney 293 (hek293) cell model using site directed mutagenesis and phosphopeptide mapping analysis. In hek293 cells, phosphorylation of these sites occurred at a basal level and down-regulated constitutive nox1 activity. I	SIGNOR-163663
P04637	Q92585	2	binding	up-regulates	0.31	Unexpectedly, however, emerging evidence implicate maml proteins as exciting key transcriptional co-activators in other signal transduction pathways including: muscle differentiation and myopathies (mef2c), tumor suppressor pathway (p53) and colon carcinoma survival (beta-catenin).	SIGNOR-180136
O15534	P48729	0	phosphorylation	down-regulates quantity by destabilization	0.318	CKI\u03b1-Dependent Phosphorylation and Degradation of PER1.	SIGNOR-279700
P05129	Q7Z2E3	1	phosphorylation	up-regulates	0.32	We show the novel molecular consequences of increased kinase activities of mutants: aprataxin (aptx), a dna repair protein causative for autosomal recessive ataxia, was found to be a preferential substrate of mutant pkc gamma, and phosphorylation inhibited its nuclear entry. ollectively, phosphorylation occurred at thr111, reducing nuclear aptx.	SIGNOR-186409
Q00535	P10636	1	phosphorylation	down-regulates activity	0.763	We found that cdk5 phosphorylated tau(441) at Thr-181, Ser-199, Ser-202, Thr-205, Thr-212, Ser-214, Thr-217, Thr-231, Ser-235, Ser-396, and Ser-404, but not at Ser-262, Ser-400, Thr-403, Ser-409, Ser-413, or Ser-422. GSK-3beta phosphorylated all the cdk5-catalyzed sites above except Ser-235.	SIGNOR-249321
P07948	Q8N6F7	1	phosphorylation	up-regulates activity	0.245	Herein, we demonstrate phosphorylation of HGAL by Syk and Lyn kinases at tyrosines Y80, Y86, Y106Y107, Y128, and Y148. Y148 (in black) was already phosphorylated before the addition of kinases. We demonstrate that Grb2 facilitates HGAL and Syk binding following BCR stimulation but does not affect the HGAL-mediated increase in Syk kinase activity. Previous studies showed that Grb2 inhibits BCR signaling by decreasing the activation of Syk by Lyn.11 Thus, while HGAL and Grb2 oppositely affect Syk kinase activity, this is not due to direct Grb2 effects on HGAL-mediated Syk kinase activation.	SIGNOR-273560
P24752	Q9P0J1	1	acetylation	down-regulates activity	0.34	We previously reported that the mitochondrial fraction of FLT3 activates acetyl-CoA acetyltransferase ACAT1 in mitochondria via Y407 phosphorylation to acetylate and inhibit mitochondrial pyruvate dehydrogenase A (PDHA) and PDH phosphatase 1 (PDP1)	SIGNOR-267635
P04150	P05412	1	transcriptional regulation	down-regulates quantity by repression	0.743	We have described how the receptor uses several means to achieve repression of the genes regulated by AP-1 and NF-KB proteins	SIGNOR-251679
Q9P2S2	Q8NFZ4	2	binding	up-regulates activity	0.829	The neurexin–NL2 interaction is sufficient to induce GABAergic differentiation and clustering of GABAARs at postsynaptic sites	SIGNOR-265454
Q99801	Q13315	0	phosphorylation	down-regulates quantity by destabilization	0.362	ATM phosphorylates NKX3.1 on T166 and then T134, resulting in NKX3.1 ubiquitination and degradation resulting from an apparent regulatory interaction.	SIGNOR-276499
P08631	P40763	1	phosphorylation	up-regulates activity	0.618	Activation of STAT3 by the Src family kinase Hck requires a functional SH3 domain. Direct Phosphorylation of STAT3 on Tyr-705 by Src Family Kinases	SIGNOR-251267
Q5TEC6	Q9UIF8	2	binding	down-regulates activity	0.2	The BAZ2B bromodomain has been shown to bind to acetylated H3K14 (H3K14ac), whose presence at promoter regions is generally associated with gene activation. This suggests a potential role for BAZ2B in transcriptional activation.	SIGNOR-266618
Q6P5Z2	P56945	2	binding	up-regulates activity	0.2	Taken together, the data suggest that p130Cas expression induces PKN3 activation and this activation is independent of p130Cas–PKN3 interaction.	SIGNOR-264573
P05546	P08311	0	cleavage	down-regulates activity	0.444	Amino acid sequence analysis led to the conclusion that both neutrophil elastase and cathepsin G cleave HC at Ile66, which does not affect HC activity, and at Val439, near the reactive site Leu444, which inactivates HC.	SIGNOR-256509
P04637	P11413	2	binding	down-regulates activity	0.583	The p53 protein binds to glucose-6-phosphate dehydrogenase (G6PD), the first and rate-limiting enzyme of the PPP, and prevents the formation of the active dimer.	SIGNOR-267468
P06239	P04150	2	binding	up-regulates	0.355	The present study shows that the GC receptor is part of a TCR-linked multiprotein complex containing heat-shock protein (HSP)90, LCK and FYN, which is essential for TCR-dependent LCK/FYN activation.	SIGNOR-251685
P53350	P06493	2	binding	up-regulates activity	0.611	Moreover, CDK1 phosphorylates RSF1 at Ser1375, and this phosphorylation is necessary for PLK1 recruitment. Subsequently, PLK1 phosphorylates RSF1 at Ser1359, stabilizing PLK1 deposition.	SIGNOR-273589

P50148

Q92847

2

binding

up-regulates activity

0.474

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-257380

P00519

Q9UPY6

1

phosphorylation

up-regulates activity

0.582

WAVE3-Abl interaction promotes the tyrosine phosphorylation of WAVE3 by Abl, and STI-571, a specific inhibitor of Abl kinase activity, abrogates the Abl-mediated phosphorylation of WAVE3.

SIGNOR-259077

P98170

Q9NR28

2

ubiquitination

down-regulates quantity by destabilization

0.914

Xiap functions as ubiquitin ligase toward smac to inhibit apoptosis.

SIGNOR-134504

Q9BRV8

Q9UHD2

0

phosphorylation

down-regulates quantity

0.718

Mechanism of endogenous regulation of the type I interferon response by suppressor of I\u03baB kinase epsilon (SIKE), a novel substrate of TANK-binding kinase 1 (TBK1).|TBK1 phosphorylation of IRF3 and SIKE displayed negative cooperativity.

SIGNOR-280152

Q8NFZ4

Q9P2S2

2

binding

up-regulates activity

0.829

Pre- and postsynaptic plasma membranes are always precisely aligned, and are separated by a synaptic cleft of ~20 nm. The cleft contains an undefined proteinaceous material in the middle, and is presumably bridged by synaptic cell-adhesion molecules such as Nrxns and Nlgns that align the pre- and postsynaptic elements and mediate trans-synaptic signaling.|Nlgns bind to both alpha- and beta-Nrxns with nanomolar affinities; binding involves the sixth LNS-domain of alpha-Nrxns which corresponds to the only LNS-domain of beta-Nrxns52. The binding affinities differ characteristically between various pairs of Nlgns and Nrxns, and are controlled by alternative splicing of both Nrxns and Nlgns (Figure 1c)

SIGNOR-264156

P98177

P16220

2

binding

down-regulates activity

0.308

We provide evidence that the acetyltransferase creb-binding protein (cbp) binds foxo resulting in acetylation of foxo. This acetylation inhibits foxo transcriptional activity

SIGNOR-124711

O14920

P35813

0

dephosphorylation

down-regulates

0.308

Using a functional genomic approach, we have identified two protein serine/threonine phosphatases, ppm1a and ppm1b, as ikkbeta phosphatases. Overexpression of ppm1a or ppm1b results in dephosphorylation of ikkbeta at ser177 and ser181 and termination of ikkbeta-induced nf-kappab activation

SIGNOR-181659

P36956

P49327

1

transcriptional regulation

up-regulates quantity by expression

0.495

Ultimately, both the AKT and MAPK transduction pathways regulate FASN expression through the modulation of expression of sterol regulatory element-binding protein (SREBP)-1c, which binds to regulatory elements in the FASN promoter. Proto-oncogene FBI-1 (Pokemon), a transcription factor of the bric--brac tramtrack broad complex/pox viruses and zinc fingers (BTB/POZ) domain family, interacts directly with SREBP-1c through its DNA-binding domain to synergistically activate the transcription of FASN

SIGNOR-242884

Q9NZP8

P00738

1

cleavage

up-regulates activity

0.375

We demonstrate that coexpression of the proform of Hp (proHp) and C1r-LP in COS-1 cells effected cleavage of proHp in the endoplasmic reticulum. This cleavage depended on proteolytic activity of C1r-LP because mutation of the putative active-site Ser residue abolished the reaction. Furthermore, incubation of affinity-purified C1r-LP and proHp led to the cleavage of the latter protein. ProHp appeared to be cleaved at the expected site because substitution of Gly for Arg-161 blocked the reaction.

SIGNOR-256358

P31749

P84243

1

phosphorylation

down-regulates activity

0.2

Additionally, active akt1 kinase strongly phosphorylates histone h3 at serine 10 in vitro

SIGNOR-98285

O14793

Q13705

2

binding

up-regulates activity

0.642

The purified C-terminal myostatin dimer was capable of binding the activin type II receptors, Act RIIB and, to a lesser extent, Act RIIA

SIGNOR-235153

P04637

P45984

0

phosphorylation

up-regulates

0.747

These findings strongly suggest that jnks are the major direct signaling mediators of uvb-induced p53 phosphorylation at serine 20. furthermore, phosphorylation of p53 at serine 20 by uvb-activated jnks and uvb-induced p53-dependent transcriptional activity were suppressed in jnk1 or jnk2 knockout (jnk1(-/-) or jnk2(-/-)) cells.

SIGNOR-115835

Q07820

P49840

0

phosphorylation

down-regulates quantity by destabilization

0.457

MCL-1 was phosphorylated by GSK-3 at a conserved GSK-3 phosphorylation site (S159). Glycogen Synthase Kinase-3 Regulates Mitochondrial Outer Membrane Permeabilization and Apoptosis by Destabilization of MCL-1. threonine 163, which represents the GSK-3 priming phosphorylation in this protein

SIGNOR-251217

P00533

O43639

2

binding

up-regulates

0.399

Growth factor binding to receptor protein tyrosine kinases (r-ptks)1 induces their dimerization and trans-phosphorylation, creating docking sites for proteins containing sh2 and ptb protein interaction domains. Nck binds to the pdgf and egfr receptors (figure 3c).

SIGNOR-64731

Q05655

Q96C90

1

phosphorylation

up-regulates activity

0.2

Recombinant tagged PHI-1 was phosphorylated by protein kinase C at two sites, one a Ser and one a Thr; phosphorylation enhanced inhibitory potency 50-fold.

SIGNOR-265739

Q9BVG3

Q9H257

1

ubiquitination

up-regulates activity

0.51

Importantly, using in vitro ubiquitination assays with purified proteins, we verified that CARD9 is directly ubiquitinated by TRIM62 at residue K125; this ubiquitination is dependent on the ligase activity of TRIM62 and does not occur in CARD9 Delta11 (XREF_FIG).

SIGNOR-278552

Q14332

P41221

2

binding

down-regulates

0.766

Fz2 was also required for the wnt3a-dependent accumulation of beta-catenin, and wnt5a competed with wnt3a for binding to fz2 in vitro and in intact cells, thereby inhibiting the beta-catenin pathway.

SIGNOR-23441

Q99959

P15924

2

binding

up-regulates quantity by stabilization

0.787

In contrast to the proper membrane localization of PKP2 and DSP after cotransfection of both WT proteins, mutant PKP2 C796R protein was not able to interact with FLAG-DSP to enable assembly at the junctional plaque, indicating the requirement of functional PKP2 for DSP integration into the desmosome.

SIGNOR-261254

P03951

P01008

0

cleavage

down-regulates activity

0.657

Antithrombin (AT), a member of the serine protease inhibitor (SERPIN) superfamily, is a major circulating inhibitor of blood coagulation proteases such as factor (F) IIa (known as thrombin), FXa and, to a lesser extent, FIXa, FXIa and FXIIa. SERPINC1, which encodes AT in humans, is located on chromosome 1q25.1

SIGNOR-264137

O00418

P23443

0

phosphorylation

down-regulates activity

0.736

We show that two such kinases, p70 s6 kinase (regulated via mtor) and p90(rsk1) (activated by erk), phosphorylate eef2k at a conserved serine and inhibit its activity

SIGNOR-109712

P60484

P53350

0

phosphorylation

down-regulates activity

0.534

Subsequently, Plk1 phosphorylation of PTEN was shown to be responsible for its inactivation.

SIGNOR-280070

P04637

Q13131

0

phosphorylation

up-regulates

0.48

Ampk activation induces phosphorylation of p53 on serine 15, and this phosphorylation is required to initiate ampk-dependent cell-cycle arrest

SIGNOR-135960

P08243

P08047

0

transcriptional regulation

up-regulates quantity by expression

0.2

Sp1 and Sp3 Activate Transcription Driven by the AS Promoter

SIGNOR-268019

P33076

P48382

2

binding

up-regulates activity

0.759

RFX5 can activate transcription only in cooperation with CIITA. RFX5 and CIITA associate to form a complex capable of activating transcription from class II major histocompatibility complex promoters. In this complex, promoter specificity is determined by the DNA binding domain of RFX5 and the general transcription apparatus is recruited by the acidic activation domain of CIITA.

SIGNOR-240980

P36896

Q15796

1

phosphorylation

up-regulates activity

0.802

ActRIIB, and then partners with a type I receptor, either activin receptor-like kinase 4 (ALK4 or ActRIB) or ALK5 (T²RI), to induce phosphorylation of Smad2/Smad3 and activate a TGF-²-like signaling pathway

SIGNOR-235157

P63244

Q9P126

2

binding

down-regulates quantity by destabilization

0.2

In this study, we reported that RACK1, the receptor for activated C-kinase 1, associated with the cytoplasmic tail of CLEC-2. Moreover, overexpression of RACK1 decreased the stability of CLEC-2 through promoting its ubiquitin-proteasome degradation, without impairing surface expression and downstream signaling of CLEC-2. Taken together, these results suggest RACK1 as a novel modulator of CLEC-2 expression.Previous reports indicated that RACK1 mediated ubiquitin–proteasome degradation of HIF-1a and BimEL by recruiting Elongin-C/B ubiquitin ligase complex

SIGNOR-272781

P10644

Q5VU43

2

binding

up-regulates

0.315

Mmgl acts as a dual-specific akap by anchoring pka regulatory isoforms r1a and r2a.

SIGNOR-173769

P11831

P54821

2

binding

up-regulates

0.442

The human homeodomain proteinphox1interacts functionally with serum response factor (srf) to impart serum responsive transcriptional activity to srf-binding sites in a hela cell cotransfection assay.

SIGNOR-52657

P31749

P14598

1

phosphorylation

up-regulates

0.559

Akt phosphorylates p47phox and mediates respiratory burst activity in human neutrophils. A direct interaction between p47(phox) and akt was shown. Active recombinant akt phosphorylated recombinant p47(phox) in vitro. Mutation analysis indicated that 2 aa residues, ser(304) and ser(328), were phosphorylated by akt. Inhibition of akt activity also inhibited fmlp-stimulated neutrophil chemotaxis.

SIGNOR-252586

Q06187

P50148

2

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

O43516

O00401

2

binding

up-regulates activity

0.933

Recruitment of N-WASP to vaccinia is mediated by WASP-interacting protein (WIP), whereas in Shigella WIP is recruited by N-WASP. Our observations show that vaccinia and Shigella activate the Arp2/3 complex to achieve actin-based motility, by mimicking either the SH2/SH3-containing adaptor or Cdc42 signalling pathways to recruit the N-WASP-WIP complex.

SIGNOR-261880

P35222

P31749

0

phosphorylation

up-regulates

0.805

Phosphorylation of beta-catenin by akt promotes beta-catenin transcriptional activity|we have demonstrated that akt phosphorylates beta-catenin at ser552 in vitro and in vivo.

SIGNOR-252499

Q96PH1

P17252

0

phosphorylation

up-regulates

0.2

A constitutively active form of pkc? Robustly increased basal and pma-stimulated nox5 activity and promoted the phosphorylation of nox5 on ser490, thr494, and ser498.

SIGNOR-204550

Q13002

P17612

0

phosphorylation

up-regulates activity

0.2

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

SIGNOR-250315

Q16539

P78536

1

phosphorylation

up-regulates activity

0.405

We show that p38 MAP kinase, which is activated in response to inflammatory or stress signals, directly activates TACE, a membrane-associated metalloprotease that is also known as ADAM17 and effects shedding in response to growth factors and Erk MAP kinase activation. p38alpha MAP kinase interacts with the cytoplasmic domain of TACE and phosphorylates it on Thr(735), which is required for TACE-mediated ectodomain shedding

SIGNOR-163970

Q13105

Q7Z6Z7

0

ubiquitination

down-regulates quantity by destabilization

0.327

Previously, we reported that K48 linked polyubiquitination of Miz1 by Mule triggers its proteasomal degradation, thereby relieving Miz1 suppression on TNF induced JNK activation and apoptosis.

SIGNOR-278697

P35813

P50750

1

dephosphorylation

down-regulates activity

0.493

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

SIGNOR-248490

P42702

P26441

2

binding

up-regulates

0.742

Ciliary neurotrophic factor (cntf) is a cytokine supporting the differentiation and survival of various cell types in the peripheral and central nervous systems. Its receptor complex consists of a non-signaling alpha chain, cntfr, and two signaling beta chains, gp130 and the leukemia inhibitory factor receptor (lifr)

SIGNOR-81382

P55273

P24941

0

phosphorylation

up-regulates

0.526

Cdk2 and pka were found to participate in p19ink4d phosphorylation process and that they would mediate serine 76 and threonine 141 modifications respectively. Nuclear translocation of p19ink4d induced by dna damage was shown to be dependent on serine 76 phosphorylation.

SIGNOR-197270

O95155

Q99689

1

polyubiquitination

up-regulates activity

0.391

E4B mediated the polyubiquitylation of FEZ1 but did not affect its intracellular stability, suggesting that such modification of FEZ1 is not a signal for its proteolysis. Polyubiquitylation of FEZ1 by E4B required Lys(27) of ubiquitin. Expression of a dominant-negative mutant of E4B in rat pheochromocytoma PC12 cells resulted in inhibition of neurite extension induced either by nerve growth factor or by coexpression of FEZ1 and constitutively active PKCzeta. These findings indicate that E4B serves as a ubiquitin ligase for FEZ1 and thereby regulates its function but not its degradation. The polyubiquitin chain attached by E4B to FEZ1 might therefore facilitate the interaction of FEZ1 with an unidentified target that functions in neuritogenesis.

SIGNOR-271510

O14920

Q92574

1

phosphorylation

down-regulates

0.642

Here we show that ikkbeta, a major downstream kinase in the tnfalpha signaling pathway, physically interacts with and phosphorylates tsc1 at ser487 and ser511, resulting in suppression of tsc1phosphorylation of tsc2 (by akt and erk;refs. 28, 29) and tsc1(by ikkbeta;ref. 30) results in the disruption of the tsc1/2 complex, and thereby activates the oncogenic mtor signaling contributing to tumor progression.

SIGNOR-157296

Q92585

P62805

1

acetylation

down-regulates activity

0.2

We speculated that maml1, in addition to recruiting p300, might directly interact with histones to facilitate histone acetylation. We had observed acetylation of the histones h3 and h4.

SIGNOR-153041

Q9UDY2

Q9GZV5

2

binding

down-regulates

0.507

In addition, yap and taz interact with another tight junction protein zo-2, which was reported to increase nuclear localization of yap and tight-junction localization of taz.

SIGNOR-175931

Q00987

P49137

0

phosphorylation

up-regulates quantity by stabilization

0.364

Hdm2 phosphorylation by mapkap kinase 2 enhances hdm2 activity and promote the degradation of p53.

SIGNOR-133560

P84243

P83916

2

binding

up-regulates activity

0.2

A core characteristic of heterochromatin is its association with heterochromatin protein 1 (HP1) proteins, a highly conserved family of chromosomal proteins that bind to di- and trimethylated H3K9 via a conserved N-terminal domain called the chromodomain (CD) HP1 proteins are a highly conserved family of eukaryotic proteins that bind to methylated histone H3 lysine 9 (H3K9) and are required for heterochromatic gene silencing.

SIGNOR-264491

Q86UR5

A6NNM3

2

binding

down-regulates activity

0.345

SH3 domains of RBPs interact with RIMs. The enhancement of depolarization-induced secretion in PC12 cells by fusion proteins that suppress the associations of RBPs with RIMs and α1 suggests that RBPs may repress RIMs, either directly or through associated proteins.

SIGNOR-264364

P17612

O96004

1

phosphorylation

down-regulates activity

0.296

In vitro and in vivo phosphorylation studies show that both PKA and PKC can phosphorylate HAND1 and -2. T107; S109 within helix I and S98 within the basic domain, are the phosphorylated residues. We determined that modification of HAND1 at residues 107 and 109 affects dimerization affinities with E-proteins, thus changing the bHLH dimer equilibrium within the cell. These modifications also affect HAND1 function.

SIGNOR-249991

Q07812

O15297

0

dephosphorylation

down-regulates activity

0.2

34 In this study, a novel function of Wip1 was identified, that is, its ability to dephosphorylate directly and thus inactivate apoptotic BAX protein in response to gamma irradiation.|To ascertain whether Wip1 dephosphorylates BAX, recombinant Wip1 was incubated with previously reported BAX-derived phosphopeptides containing Ser87, Ser163, Thr167, and Ser184 in an in vitro phosphatase assay. xref , xref Peptides containing phospho-Thr180 from p38 MAPK and phospho-Thr31 from UNG2 were used as a positive and negative control, respectively. xref As shown in xref , purified Wip1 did not dephosphorylate the four BAX-derived phosphopeptides.

SIGNOR-276993

Q9UJU2

P19883

1

transcriptional regulation

up-regulates quantity by expression

0.28

We further demonstrate that Fst is a direct target of the WNT/β-catenin pathway. Activation and inactivation of β-catenin induced and inhibited Fst expression, respectively, in both C2C12 cells and mouse embryos. Specific TCF/LEF1 binding sites within the promoter and intron 1 region of the Fst gene were required for RSPO2 and WNT/β-catenin-induced Fst expression.

SIGNOR-251722

P04626

Q05209

0

dephosphorylation

down-regulates activity

0.619

In MDA-MB-231 cells, a human triple negative breast cancer cell line, phosphorylation of PTPN12 on Ser 19 was increased in response to cyclin dependent kinase 2 (CDK2), and this impaired PTPN12 's ability to dephosphorylate HER2 on Y1196.|PTPN12 negatively regulates Her2, by dephosphorylation on Tyr 1196 on Her2.

SIGNOR-277038

Q13114

P29350

0

dephosphorylation

down-regulates activity

0.2

We identified a direct interaction between SHP‐1 and TRAF3; the association between these two proteins resulted in diminished recruitment of CK1ε to TRAF3 and inhibited its K63‐linked ubiquitination; SHP‐1 inhibited K63‐linked ubiquitination of TRAF3 by promoting dephosphorylation at Tyr116 and Tyr446.

SIGNOR-277527

Q8NFG4

Q9HB90

1

gtpase-activating protein

up-regulates activity

0.695

The folliculin tumor suppressor is a GAP for the RagC/D GTPases that signal amino acid levels to mTORC1 [..} RagC/D is a key regulator of the interaction of mTORC1 with the Rag heterodimer and that, unexpectedly, RagC/D must be GDP-bound for the interaction to occur

SIGNOR-256503

P17612

O14921

1

phosphorylation

up-regulates quantity by stabilization

0.334

Phosphorylation of RGS13 by the cyclic AMP-dependent protein kinase inhibits RGS13 degradation.we show that PKA activation also leads to increased steady-state RGS13 expression through RGS13 phosphorylation, which inhibits RGS13 protein degradation. RGS13 phosphorylation was diminished by mutation of an N-terminal Thr residue (T41) identified as a phosphorylation site by mass spectrometry.

SIGNOR-259835

Q01892

P19784

0

phosphorylation

down-regulates quantity by destabilization

0.307

Phosphorylation of the Spi-B transcription factor reduces its intrinsic stability. | Serine residues 37 in the transactivation domain and 129, 144 and 146 in the PEST domain of Spi-B are phosphorylated by CKII in vitro | The CKII phosphorylation sites mapped in vitro are phosphorylated in vivo

SIGNOR-251042

Q08211

Q99836

2

binding

up-regulates activity

0.491

We further showed that both DHX9 and DHX36 are localized within the cytosol and are directly bound to the Toll-interleukin receptor domain of MyD88 via their helicase-associated domain 2 and DUF domains. This study demonstrates that DHX9/DHX36 represent the MyD88-dependent DNA sensors in the cytosol of pDCs and suggests a much broader role for DHX helicases in viral sensing.

SIGNOR-260955

P52333

P08575

0

dephosphorylation

down-regulates activity

0.456

CD45 is a JAK phosphatase and negatively regulates cytokine receptor signalling

SIGNOR-248359

Q96KS0

P17252

0

phosphorylation

down-regulates

0.364

Thus, recombinant phd1 was examined for in vitro phosphorylation using protein kinase a, protein kinase calpha, casein kinase i and ii and erk2. The protein was most strongly phosphorylated by protein kinase calpha, and the phosphorylation sites were found to be ser-132, ser-226 and ser-234.Mutation Of ser-132 or ser-234 to asp or glu diminished the enzymatic activity to 25-60%, while mutation of ser-226 scarcely influenced the activity.

SIGNOR-180203

Q7Z434

Q14258

0

polyubiquitination

down-regulates quantity by destabilization

0.77

We report here that RLR activation triggers MAVS ubiquitination on lysine 7 and 10 by the E3 ubiquitin ligase TRIM25 and marks it for proteasomal degradation concomitantly with downstream signaling.

SIGNOR-272042

P42680

Q06187

2

phosphorylation

down-regulates activity

0.496

Tec family protein tyrosine kinases (TFKs) play a central role in hematopoietic cellular signaling. Initial activation takes place through specific tyrosine phosphorylation situated in the activation loop. Further activation occurs within the SH3 domain via a transphosphorylation mechanism, which for Bruton's tyrosine kinase (Btk) affects tyrosine 223.|In Btk, the SH3 domain mutation Y223F results in enhanced fibroblast transformation, implying that the SH3 domain may play a negative regulatory role

SIGNOR-246652

Q9ULJ6

P10275

2

binding

up-regulates activity

0.709

Our results demonstrate that hZimp10 is a novel AR interacting protein that augments AR-mediated transcription. Moreover, hZimp10 co-localized with AR and SUMO-1 at replication foci throughout S phase, and it was capable of enhancing sumoylation of AR in vivo.

SIGNOR-263935

P07197

Q9HCK8

0

transcriptional regulation

down-regulates quantity

0.2

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

SIGNOR-268917

O95150

Q93038

2

binding

up-regulates

0.776

The ligand of dr3 is tl1a

SIGNOR-103078

O75914

Q05682

1

phosphorylation

down-regulates

0.2

We investigated the effects of phosphorylation by p(21)-activated kinase 3 (pak) and calmodulin on the 22 kda c-terminal fragment of caldesmon (cad22). We substituted the major pak sites, ser-672 and ser-702, with either alanine or aspartic acid to mimic nonphosphorylated and constitutively phosphorylated states of caldesmon, respectively. Phosphorylation at these sites weakened ca(2+)-calmodulin binding further and reduced the inhibitory activity of cad22 in the absence of ca(2+)-calmodulin.

SIGNOR-167976

P49683

Q14344

2

binding

up-regulates activity

0.264

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-257280

O60260

Q13002

1

ubiquitination

down-regulates quantity by destabilization

0.2

Parkin interacts with and ubiquitinates the GluK2 KAR subunit and regulates GluK2 levels and KAR currents.|The loss of parkin function increases surface and total GluK2 levels, and consistently increases KAR currents.

SIGNOR-278541

P10912

P43378

0

dephosphorylation

down-regulates activity

0.314

Protein tyrosine phosphatases (PTPs) play key roles in switching off tyrosine phosphorylation cascades, such as initiated by cytokine receptors. We have used substrate-trapping mutants of a large set of PTPs to identify members of the PTP family that have substrate specificity for the phosphorylated human GH receptor (GHR) intracellular domain. Among 31 PTPs tested, T cell (TC)-PTP, PTP-beta, PTP1B, stomach cancer-associated PTP 1 (SAP-1), Pyst-2, Meg-2, and PTP-H1 showed specificity for phosphorylated GHR

SIGNOR-248505

Q12888

Q9Y468

2

binding

down-regulates activity

0.404

L3MBTL1, a tumor suppressor with high affinity for H4K20me2, can block 53BP1 binding at DSBs

SIGNOR-262059

P53350

P47736

1

phosphorylation

down-regulates

0.452

Plk1 phosphorylates ser525 in conserved 524dsghvs529 degron of rap1gap and promotes its interaction with _-trcp. Together, these results further support a model in which plk1, but not cdk1 or gsk-3_-mediated phosphorylation of rap1gap is a prerequisite for mitotic degradation.

SIGNOR-205577

Q7L5N7

P49137

0

phosphorylation

up-regulates activity

0.2

Mass spectrometry and mutagenesis analyses identified Ser34 of LPCAT2 as the phosphorylation site to enhance the catalytic activities. The experiments using inhibitors and siRNA against MAPK cascades demonstrated that LPCAT2 phosphorylation through LPS-TLR4 signaling may directly depend on MAPK-activated protein kinase 2 (MAPKAP kinase 2 or MK2).

SIGNOR-263077

P68400

P30622

1

phosphorylation

up-regulates

0.293

Herein, we have identified polo-like kinase 1 (plk1) and casein kinase 2 (ck2) as two kinases of clip-170 and mapped s195 and s1318 as their respective phosphorylation sites.Plk1- and ck2-associated phosphorylations of clip-170 are involved in the timely formation of kinetochore-microtubule attachments in mitosis

SIGNOR-167168

Q9P286

2

phosphorylation

up-regulates activity

0.2

Active form of Cdc42, but not Rac1 and Rho, protein was able to activate the purified GST-Pak5 autophosphorylation and kinase activity. Mutations of Pak5, which disrupted the interaction of Cdc42 and Pak5, also abolished the induction of autophosphorylation. The H19L/H22L mutant of Pak5 was insensitive to the Cdc42-induced autophosphorylation.

SIGNOR-250248

O95967

P28300

2

binding

up-regulates activity

0.561

Fibulin-4 directly binds LOX, and this interaction enhances fibulin-4 binding to tropoelastin, thus forming a ternary complex that may be critical for elastin cross-linking.

SIGNOR-252135

O00253

P41968

2

binding

down-regulates activity

0.592

AGRP is a potent antagonist of the melanocortin-3 receptor and the MC4R and has also been shown to have a lesser degree of inhibitory action at the melanocortin-5 receptor.

SIGNOR-252380

P68400

Q2V2M9

1

phosphorylation

down-regulates

0.309

We have identified a novel striated muscle-specific splice variant of the formin fhod3 that introduces a casein kinase 2 (ck2) phosphorylation site. The specific targeting of muscle fhod3 to the myofibrils in cardiomyocytes is abolished in phosphomutants or by the inhibition of ck2. Phosphorylation of muscle fhod3 also prevents its interaction with p62/sequestosome 1 and its recruitment to autophagosomes.

SIGNOR-170525

P62136

P28482

1

dephosphorylation

down-regulates

0.446

P-erk1/2 proteins were efficiently dephosphorylated in vitro by protein phosphatases 1 and 2a (pp1/2a) and mapk phosphatase 3 (mkp3)

SIGNOR-103152

P62714

P01106

1

dephosphorylation

down-regulates

0.276

Phosphorylation at ser-62 by pro-directed kinases (p-k) is a prerequisite for gsk3-dependent phosphorylation of thr-58. This triggers binding of pin1, subsequently protein phosphatase 2a (pp2a)-dependent dephosphorylation of ser-62, and then recruitment of scf-fbw7 to the thr-58-phosphorylated myc. Scf-fbw7 polyubiquitinylates myc (branching through lys-48), leading to its proteasomal degradation.

SIGNOR-149726

Q99814

P27361

0

phosphorylation

up-regulates quantity by stabilization

0.26

The activation of ERK1/2 upon hypoxia promoted HIF-2alpha phosphorylation, enhancing its interaction with USP33.Here, we identified USP33 as essential deubiquitinase that stabilizes HIF-2alpha protein in an ERK1/2-dependent manner to promote hypoxia response in cancer cells.

SIGNOR-277584

P18031

O15344

0

ubiquitination

down-regulates quantity

0.2

Proteasome inhibitor treatment diminished the decrease of PTP1B (Figure 5F) caused by TRIM18 overexpression.|TRIM18 Interacts With PTP1B and Promotes PTP1B Ubiquitination.

SIGNOR-278703

Q96EB6

Q96EP1

0

ubiquitination

down-regulates quantity

0.372

CHFR binds to and ubiquitylates SIRT1, leading to its proteasomal degradation.|CHFR ubiquitylates and promotes the proteasomal degradation of SIRT1.

SIGNOR-278691

O43542

Q13535

0

phosphorylation

up-regulates activity

0.464

HXRCC3 S225 phosphorylation is mediated by ATR via an ATM-dependent signaling pathway. These data clearly indicate that ATR mediates the late activation of XRCC3 following DSB accumulation.

SIGNOR-262666

Q08828

P04899

2

binding

down-regulates activity

0.597

Adenylate cyclase is regulated by stimulatory hormones through Gs(alpha s beta gamma) and inhibitory hormones through Gi(alpha i beta gamma)

SIGNOR-256499

Q9P2B4

O43815

2

binding

up-regulates activity

0.645

Although CTTNBP2 and CTTNBP2NL are different in terms of tissue and subcellular distribution, our data indicate that, similar to CTTNBP2NL, CTTNBP2 associates with members of the striatin family, namely striatin and zinedin. Moreover, CTTNBP2 is critical for the distribution of striatin and zinedin in dendritic spines. The role of CTTNBP2 in the regulation of the synaptic distribution of striatin and zinedin suggests that CTTNBP2 regulates synaptic signaling through PP2A.

SIGNOR-261702

P68400

P30291

1

phosphorylation

down-regulates quantity by destabilization

0.408

In the present study, we show that phosphorylation of S123 (pS123) by CDK promoted the binding of Wee1A to beta-TrCP through three independent mechanisms. S123 phosphorylation creates a PBD-binding motif and accelerates S53 phosphorylation by Plk1.

SIGNOR-276038

P17612

Q86UR1

1

phosphorylation

down-regulates

0.324

We identified ser-282 as target of mapk and ser-172 as target of pkc and pka in vitro and in a transfected human embryonic kidney 293 (hek293) cell model using site directed mutagenesis and phosphopeptide mapping analysis. In hek293 cells, phosphorylation of these sites occurred at a basal level and down-regulated constitutive nox1 activity. I

SIGNOR-163663

P04637

Q92585

2

binding

up-regulates

0.31

Unexpectedly, however, emerging evidence implicate maml proteins as exciting key transcriptional co-activators in other signal transduction pathways including: muscle differentiation and myopathies (mef2c), tumor suppressor pathway (p53) and colon carcinoma survival (beta-catenin).

SIGNOR-180136

O15534

P48729

0

phosphorylation

down-regulates quantity by destabilization

0.318

CKI\u03b1-Dependent Phosphorylation and Degradation of PER1.

SIGNOR-279700

P05129

Q7Z2E3

1

phosphorylation

up-regulates

0.32

We show the novel molecular consequences of increased kinase activities of mutants: aprataxin (aptx), a dna repair protein causative for autosomal recessive ataxia, was found to be a preferential substrate of mutant pkc gamma, and phosphorylation inhibited its nuclear entry. ollectively, phosphorylation occurred at thr111, reducing nuclear aptx.

SIGNOR-186409

Q00535

P10636

1

phosphorylation

down-regulates activity

0.763

We found that cdk5 phosphorylated tau(441) at Thr-181, Ser-199, Ser-202, Thr-205, Thr-212, Ser-214, Thr-217, Thr-231, Ser-235, Ser-396, and Ser-404, but not at Ser-262, Ser-400, Thr-403, Ser-409, Ser-413, or Ser-422. GSK-3beta phosphorylated all the cdk5-catalyzed sites above except Ser-235.

SIGNOR-249321

P07948

Q8N6F7

1

phosphorylation

up-regulates activity

0.245

Herein, we demonstrate phosphorylation of HGAL by Syk and Lyn kinases at tyrosines Y80, Y86, Y106Y107, Y128, and Y148. Y148 (in black) was already phosphorylated before the addition of kinases. We demonstrate that Grb2 facilitates HGAL and Syk binding following BCR stimulation but does not affect the HGAL-mediated increase in Syk kinase activity. Previous studies showed that Grb2 inhibits BCR signaling by decreasing the activation of Syk by Lyn.11 Thus, while HGAL and Grb2 oppositely affect Syk kinase activity, this is not due to direct Grb2 effects on HGAL-mediated Syk kinase activation.

SIGNOR-273560

P24752

Q9P0J1

1

acetylation

down-regulates activity

0.34

We previously reported that the mitochondrial fraction of FLT3 activates acetyl-CoA acetyltransferase ACAT1 in mitochondria via Y407 phosphorylation to acetylate and inhibit mitochondrial pyruvate dehydrogenase A (PDHA) and PDH phosphatase 1 (PDP1)

SIGNOR-267635

P04150

P05412

1

transcriptional regulation

down-regulates quantity by repression

0.743

We have described how the receptor uses several means to achieve repression of the genes regulated by AP-1 and NF-KB proteins

SIGNOR-251679

Q9P2S2

Q8NFZ4

2

binding

up-regulates activity

0.829

The neurexin–NL2 interaction is sufficient to induce GABAergic differentiation and clustering of GABAARs at postsynaptic sites

SIGNOR-265454

Q99801

Q13315

0

phosphorylation

down-regulates quantity by destabilization

0.362

ATM phosphorylates NKX3.1 on T166 and then T134, resulting in NKX3.1 ubiquitination and degradation resulting from an apparent regulatory interaction.

SIGNOR-276499

P08631

P40763

1

phosphorylation

up-regulates activity

0.618

Activation of STAT3 by the Src family kinase Hck requires a functional SH3 domain. Direct Phosphorylation of STAT3 on Tyr-705 by Src Family Kinases

SIGNOR-251267

Q5TEC6

Q9UIF8

2

binding

down-regulates activity

0.2

The BAZ2B bromodomain has been shown to bind to acetylated H3K14 (H3K14ac), whose presence at promoter regions is generally associated with gene activation. This suggests a potential role for BAZ2B in transcriptional activation.

SIGNOR-266618

Q6P5Z2

P56945

2

binding

up-regulates activity

0.2

Taken together, the data suggest that p130Cas expression induces PKN3 activation and this activation is independent of p130Cas–PKN3 interaction.

SIGNOR-264573

P05546

P08311

0

cleavage

down-regulates activity

0.444

Amino acid sequence analysis led to the conclusion that both neutrophil elastase and cathepsin G cleave HC at Ile66, which does not affect HC activity, and at Val439, near the reactive site Leu444, which inactivates HC.

SIGNOR-256509

P04637

P11413

2

binding

down-regulates activity

0.583

The p53 protein binds to glucose-6-phosphate dehydrogenase (G6PD), the first and rate-limiting enzyme of the PPP, and prevents the formation of the active dimer.

SIGNOR-267468

P06239

P04150

2

binding

up-regulates

0.355

The present study shows that the GC receptor is part of a TCR-linked multiprotein complex containing heat-shock protein (HSP)90, LCK and FYN, which is essential for TCR-dependent LCK/FYN activation.

SIGNOR-251685

P53350

P06493

2

binding

up-regulates activity

0.611

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

SIGNOR-273589