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
Q15759	O75582	1	phosphorylation	up-regulates	0.615	Mitogen- and stress-activated protein kinase-1 (msk1) is directly activated by mapk and sapk2/p38, and may mediate activation of crebactivated by phosphorylation at ser-360, thr-581 and thr-700 by mapk1/erk2, mapk3/erk1 and mapk14/p38-alpha	SIGNOR-59443
P04637	P53778	0	phosphorylation	up-regulates activity	0.474	Furthermore, upon activation by oncogenic ras, p38gamma stimulated the transcriptional activity of p53 by phosphorylating p53 at Ser(33), suggesting that the ability of p38gamma to mediate senescence is at least partly achieved through p53.	SIGNOR-280026
O15111	O14920	1	phosphorylation	up-regulates activity	0.67	Our data indicate that IKKα stimulates IKKβ kinase activity for the IκBα substrate. Finally, we demonstrate that IKKα can phosphorylate IKKβ in in vitro kinase assays.	SIGNOR-250772
Q99835	Q9UBI6	2	binding	up-regulates	0.2	As pka suppresses the activity of gli, smo might use the stimulation of pi3k by galfai and gbetagamma subu- nits to block pka in cells that have high levels of camp.	SIGNOR-152817
P01106	P50750	0	phosphorylation	down-regulates activity	0.54	CDK9 promotes phosphorylation of MYC on Ser 62 .	SIGNOR-279024
P05129	P06127	1	phosphorylation	up-regulates	0.341	Cd5 is a good pkc substrate. Phosphorylation of cd5 is necessary for cd5-mediated lipid second messenger generation.	SIGNOR-85183
P43405	Q9GZY6	1	phosphorylation	up-regulates activity	0.592	Our results indicated that human LAB was primarily phosphorylated on three membrane-distal tyrosines, Tyr(136), Tyr(193), and Tyr(233). Mutation of these three tyrosines abolished Grb2 binding and LAB function. Our data suggested that these tyrosines are the most important tyrosines for LAB function.The dramatic reduction in phosphorylation of the LAB Y233F mutant suggested that Tyr233 is a primary target of the Syk family kinases.	SIGNOR-273576
P49841	P04198	1	phosphorylation	down-regulates quantity by destabilization	0.33	Because GSK3\u03b2 phosphorylates Nmyc at T58, we assessed GSK3\u03b2 activation in Dex-treated MB cells.	SIGNOR-279722
P38405	O00254	2	binding	up-regulates activity	0.2	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-256904
P06493	Q8NHV4	1	phosphorylation	up-regulates activity	0.585	Here we report that the function of Nedd1 is regulated by Cdk1 and Plk1. During mitosis, Nedd1 is firstly phosphorylated at T550 by Cdk1, which creates a binding site for the polo-box domain of Plk1. Then, Nedd1 is further phosphorylated by Plk1 at four sites: T382, S397, S637 and S426. The sequential phosphorylation of Nedd1 by Cdk1 and Plk1 promotes its interaction with gamma-tubulin for targeting the gammaTuRC to the centrosome and is important for spindle formation.	SIGNOR-272973
O00429	P00519	0	phosphorylation	up-regulates activity	0.26	In this study, we found that c-Abl phosphorylated Drp1 at tyrosine 266, 368 and 449 in vitro and in vivo, which augmented the GTPase activity of Drp1 and promoted Drp1-mediated mitochondrial fragmentation.	SIGNOR-277328
P04637	Q92630	0	phosphorylation	up-regulates	0.67	Here, we demonstrate that the dual-specificity tyrosine-phosphorylation-regulated kinase 2 (dyrk2) directly phosphorylates p53 at ser46. these findings indicate that dyrk2 regulates p53 to induce apoptosis in response to dna damage.	SIGNOR-153544
Q92847	Q9UBU3	2	binding	up-regulates	0.722	In contrast to wild-type mice, acute treatment of ghsr- mice with ghrelin stimulated neither gh release nor food intake, showing that the ghsr is a biologically relevant ghrelin receptor.	SIGNOR-123948
Q14444	Q13283	2	binding	up-regulates activity	0.588	Caprin-1 and G3BP-1 were directly or indirectly associated in a stable complex. The Caprin-1/G3BP-1 complex occurs in cytoplasmic RNA granules	SIGNOR-260982
P11831	P78527	0	phosphorylation	up-regulates activity	0.406	The carboxyl-terminal transcription activation domain was mapped within a 71-amino acid region that contains both DNA-PK phosphorylation sites. Amino acid substitutions that interfered with phosphorylation by DNA-PK at Ser-435/446 in GAL4-SRF fusion proteins were reduced in transactivation potency. From these data we suggest that DNA-PK phosphorylation may modulate SRF activity in vivo.	SIGNOR-248922
P27361	P10636-2	1	phosphorylation	down-regulates activity	0.501	We have studied the relationship between the phosphorylation oftau by several kinases (MARK, PKA, MAPK, GSK3) and its assembly into PHFs. By contrast, MARK and PKA phosphorylate several sites within the repeats (notably theKXGS motifs including Ser262, Ser324, and Ser356, plus Ser320); in addition PKA phosphorylates somesites in the flanking domains, notably Ser214. This type of phosphorylation strongly reduces tau’s affinityfor microtubules, and at the same time inhibits tau’s assembly into PHFs.	SIGNOR-275434
P18846	O75676	0	phosphorylation	up-regulates	0.615	Msk1 and msk2 directly phosphorilate and activate transcription factors such as creb1, atf1.	SIGNOR-116252
O15303	P63092	2	binding	up-regulates activity	0.34	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-264084
P0DP25	P29474	2	binding	up-regulates activity	0.565	Electrons flow from the C-terminal reductase domain of one NOS monomer to the N-terminal oxygenase domain of the other NOS monomer (Siddhanta et al., 1998). The primary mode of enzyme activation is the binding of calcium-bound calmodulin to the N-terminal CaM-binding domain. This facilitates a structure change and the flow of electrons from NADPH through the flavins to the oxygenase domain of the other eNOS monomer	SIGNOR-266339
Q53GL7	Q13283	1	post translational modification	up-regulates activity	0.2	Further, we pinpoint the core SG component, G3BP1, as a PARP10 substrate and find that PARP10 regulates SG assembly driven by both G3BP1 and its modeled mechanism. Intriguingly, while PARP10 only adds a single ADP-ribose unit to proteins, G3BP1 is PARylated, suggesting its potential role as a scaffold for protein recruitment. PARP10 knockdown alters the SG core composition, notably decreasing translation factor presence.	SIGNOR-273727
Q96GD4	Q53HL2	1	phosphorylation	up-regulates activity	0.82	AURKB directly phosphorylated CDCA8 at Ser(154), Ser(219), Ser(275), and Thr(278) and seemed to stabilize CDCA8 protein in cancer cells.\|Phosphorylation and activation of cell division cycle associated 8 by aurora kinase B plays a significant role in human lung carcinogenesis.	SIGNOR-279506
Q8NB16	P30530	0	phosphorylation	up-regulates quantity by stabilization	0.2	TAM kinases phosphorylate MLKL to promote necroptosis. MLKL is then recruited to the plasma membrane, where TAM kinases phosphorylate MLKL at Tyr376 (Figure 5G, step 5), promoting its oligomerization and formation of membrane-rupturing pores that result in necrotic cell death (Figure 5G, step 6).	SIGNOR-274119
Q05901	O00468	2	binding	up-regulates activity	0.2	Treatment of muscle cells with neural agrin causes tyrosine phosphorylation of the AChR β subunit and induces AChR clustering by promoting anchoring of the receptor protein to postsynaptic cytoskeleton. Regulation of acetylcholine receptor clustering by the tumor suppressor APC. By showing a direct requirement for APC in AChR clustering, our present study suggests that the Wnt/β-catenin pathway may crosstalk with the agrin signaling cascade during the formation of mammalian neuromuscular junction.	SIGNOR-264260
P00533	Q13332	0	dephosphorylation	down-regulates activity	0.43	Similarly, Pestana et al. (89) have reported that overexpression of RPTPsigma in human A431 carcinoma cells partially inhibits EGFR activation, whereas antisense mediated suppression of RPTPsigma expression enhances EGFR activation, substrate phosphorylation, and signalling.\|These data indicate that LAR and RPTPsigma may have a significant role in GPCR induced EGFR signalling.Whereas in A431 cells LAR and RPTPsigma may act to suppress the EGFR in response to GPCR activation, it is possible that the converse may also be true in other cell types.	SIGNOR-277145
Q8IVH8	Q13233	1	phosphorylation	up-regulates	0.453	With regard to at least mekk1, serine/threonine kinases such as nik,glkand hpk1 appear also to be important for regulation	SIGNOR-61814
P25116	P63096	2	binding	up-regulates	0.402	Upon proteolysis, the newly formed n terminus acts as a tethered ligand that activates the receptor and initiates signaling cascades through multiple g proteins (galfaq, galfai, and galfa12/13).	SIGNOR-196009
Q13829	Q13618	2	binding	up-regulates activity	0.461	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-264232
Q15054	P17612	0	phosphorylation	down-regulates	0.2	In this study, we identified s458, located in the pcna-interacting protein (pip-box) motif of p68, as a phosphorylation site for pka. Phosphomimetic mutation of s458 resulted in a decrease in p68 affinity for pcna as well as the processivity of pol _.	SIGNOR-195203
Q02156	P17302	1	phosphorylation	down-regulates activity	0.44	Phosphorylation of connexin43 on serine368 by protein kinase C regulates gap junctional communication.\|These data strongly suggest that PKC directly phosphorylates Cx43 on S368 in vivo, which results in a change in single channel behavior that contributes to a decrease in intercellular communication.	SIGNOR-144465
Q14114	P06241	0	phosphorylation	up-regulates quantity	0.635	Fyn phosphorylates ApoER2.\|Together these data demonstrate that Fyn activity is necessary for its effects increasing ApoER2 levels.	SIGNOR-278197
P27361	O95997	1	phosphorylation	up-regulates	0.304	Pttg is phosphorylated in vitro on ser(162) by map kinase and this phosphorylation site plays an essential role in pttg transactivation function.	SIGNOR-79519
Q96GD4	Q9P2J3	2	binding	up-regulates activity	0.71	Aurora B Interacts with the Cul3 Complex during Mitosis and Is Ubiquitylated in a Cul3-Dependent Manner In Vivo and In Vitro. our results suggest that Cul3/KLHL9/KLHL13 activity is required to remove the chromosomal passenger protein Aurora B from mitotic chromosomes, and that Aurora B is ubiquitylated in vivo and in vitro in a KLHL9/13-dependent manner. We conclude that the Cul3/KLHL9/KLHL13 E3 ligase is an important cell-cycle regulator which, in addition to the anaphase-promoting complex (APC), coordinates mitotic progression and completion of cytokinesis.	SIGNOR-271658
P12931	P04637	1	phosphorylation	down-regulates quantity by destabilization	0.524	We recently found that ISGylation of the p53 tumor suppressor is an important novel mechanism to control its stability. Here we identified that Isg15-dependent regulation of p53 can be enhanced by different oncogenes. We further show that the Src-mediated phosphorylation of p53 on Tyr126 and Tyr220 has a positive effect on p53 ISGylation by enhancing Herc5 binding.	SIGNOR-276668
Q15796	Q13233	0	phosphorylation	up-regulates activity	0.474	As yet, the apparent discrepancy between these and above data is not clear, but obviously the type of cell under study and the cellular context may play an important role.In endothelial cells, Smad2 activity is stimulated by MEKK1, a component of the Stress Activated Protein Kinase and c-Jun N terminal kinase (SAPK and JNK) pathway.\|Phosphorylation of Smad2 by MEKK1 increased its association with Smad4, its nuclear accumulation and its transcription induction activity .	SIGNOR-279064
P19474	Q13501	1	ubiquitination	down-regulates activity	0.404	TRIM21 directly ubiquitylates p62 at residue K7 to inhibit its oligomerization and sequestration function.\|TRIM21 negatively regulates p62 mediated sequestration of Keap1 and antioxidant response.	SIGNOR-278602
P49116	Q86VZ6	2	binding	down-regulates	0.453	Tip27 interacts specifically with tak1 / tip27 functions as a tak1-selective repressor	SIGNOR-127900
Q9UKB1	Q9HAW4	1	ubiquitination	down-regulates	0.345	Claspin degradation was triggered by its interaction with, and ubiquitylation by, the scfbetatrcp ubiquitin ligase.	SIGNOR-148438
Q9NXA8	P11413	1	catalytic activity	up-regulates activity	0.278	Here, we report that SIRT5 desuccinylates and deglutarylates isocitrate dehydrogenase 2 (IDH2) and glucose-6-phosphate dehydrogenase (G6PD), respectively, and thus activates both NADPH-producing enzymes.	SIGNOR-261211
Q9NXV6	Q00987	0	ubiquitination	down-regulates	0.37	Carf interacts with hdm2 and is ubiquitinated and negatively regulated by hdm2 by proteasome-dependent degradation.	SIGNOR-160974
Q93098	O75581	2	binding	up-regulates	0.617	Wnt proteins bind to the frizzled receptors and lrp5/6 co-receptors, and through stabilizing the critical mediator betBeta-catenin, initiate a complex signaling cascade that plays an important role in regulating cell proliferation and differentiation.	SIGNOR-132027
P07947	P46937	1	phosphorylation	up-regulates activity	0.721	Yes directly phosphorylates YAP and TAZ, resulting in their increased nuclear localization and transcriptional activity.Analysis by mass spectrometry identified Tyr391 and Tyr407 as the two phosphorylation sites of YAP, whereas Tyr305 was the sole phosphorylated residue of TAZ (Fig. 5F and fig. S4, A to C).	SIGNOR-277653
O60566	O14757	0	phosphorylation	up-regulates activity	0.447	Nonetheless, in our experimental system a Chk1-dependent BubR1 phosphorylation was also observed after Noc treatment.\|Possible requirement of Chk1 in U2OS cells to activate the mitotic spindle checkpoint proteins Mad2 and BubR1.	SIGNOR-280223
P04406	Q5XX13	0	polyubiquitination	up-regulates activity	0.2	Mechanistically, FBXW10 promotes GAPDH polyubiquitination and activation; VRK2-dependent phosphorylation of GAPDH Ser151 residue is critical for GAPDH ubiquitination and activation.	SIGNOR-277841
P25963	Q14164	0	phosphorylation	down-regulates quantity by destabilization	0.484	The activated ikk complex then phosphorylates ikbalfa (an inhibitor of nf-kb) thereby targeting it for ubiquitination and proteasomal degradation.	SIGNOR-167524
P16104	O76064	0	ubiquitination	up-regulates	0.2	Rnf8 can ubiquitylate histone h2a and h2ax,	SIGNOR-159309
P68363	Q8NG68	0	tyrosination	down-regulates	0.46	Tubulin tyrosine ligase (ttl) adds a c-terminal tyr to __tubulin as part of a tyrosination/detyrosination cycle present in most eukaryotic cells. / ttl inhibits spontaneous tubulin polymerization	SIGNOR-176915
P06241	P35222	1	phosphorylation	down-regulates activity	0.851	Interaction of beta-catenin with alpha-catenin is regulated by the phosphorylation of beta-catenin Tyr-142. This residue can be phosphorylated in vitro by Fer or Fyn tyrosine kinases. Transfection of these kinases to epithelial cells disrupted the association between both catenins.	SIGNOR-251162
Q13485	P28482	0	phosphorylation	up-regulates	0.511	Phosphorylation of thr276 is shown to be important for tgf-?-Induced nuclear accumulation and, as a consequence, transcriptional activity of smad4. these results suggest that smad4 can be phosphorylated by erk2 at thr276.	SIGNOR-101660
P62826	O43592	2	binding	up-regulates activity	0.815	The first step in export appears to be the formation of a trimeric tRNA/exportin-t/RanGTP complex. tRNA and RanGTP bind to exportin-t in a highly cooperative manner: tRNA increases the affinity of exportin-t for RanGTP apparently 300-fold (Figure 5A); conversely, RanGTP has to increase the affinity of exportin-t for tRNA by the same factor. RanGTP appears to have at least two functions in this complex. First, it stabilizes the tRNA/exportin-t interaction (see Figure 4B). Second, exportin-t apparently has to bind RanGTP for rapid exit from the nucleus	SIGNOR-261392
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
P55210	Q13177	0	phosphorylation	down-regulates	0.351	Pak2 can bind with caspase-7 and phosphorylate caspase-7 at the ser-30, thr-173, and ser-239 sites. Functionally, the phosphorylation of caspase-7 decreases its activity, thereby inhibiting cellular apoptosis.	SIGNOR-173655
O43303	Q12798	2	binding	up-regulates activity	0.483	We report that CP110 interacts with two different Ca2+-binding proteins, calmodulin (CaM) and centrin, in vivo. our data demonstrate a functional role for CaM binding to CP110 and suggest that CP110 cooperates with CaM and centrin to regulate progression through cytokinesis.	SIGNOR-265966
P00519	Q92466	1	phosphorylation	down-regulates	0.458	C-abl might act as a negative regulator of uv-ddb by phosphorylating ddb2	SIGNOR-90446
O75444	P35452	2	binding	down-regulates activity	0.367	Hoxd12 and MHox, that interact with v-/c-Maf, using the phage display method. The Hox proteins also could associate with the other Maf protein family members, MafB, MafK, MafF, and MafG, but not with Jun and Fos. The Hox proteins negatively regulated the DNA binding, transactivation and cell-transforming abilities of Maf.	SIGNOR-221887
Q9UQ26	P20336	1	relocalization	up-regulates activity	0.762	N-terminal interactions of RIMs with RAB3 and MUNC13 regulate DCV fusion. Through N-terminal interactions, RIMs position MUNC13 and recruit DCVs via RAB3, which is located on the vesicle	SIGNOR-264377
P11802	Q06413	2	binding	down-regulates	0.283	In contrast to cdk2, cyclin d/cdk4 blocks myod activity through an as yet unclear mechanism that may involve direct binding. Cyclin d/cdk4 can also block the activity of myogenin and all mef2 isoforms.	SIGNOR-176518
P01111	P42338	2	binding	up-regulates	0.668	Grb2 binds and activates sos, which then activates ras, and this activates p110 independently of p85./it was also described that ras interacts with pi3k in a direct manner./lysine residue 227 is essential for the interaction of ras with pi3k	SIGNOR-175225
P51617	Q99836	2	binding	up-regulates activity	0.848	Interleukin-1 (il-1) stimulates the association of the il-1 receptor-associated protein kinase (irak) with the heterodimer of il-iri and il-iracp via the adapter protein myd88. Myd88 binds to both irak (il-1 receptor-associated kinase) and the heterocomplex (the signaling complex) of the two receptor chains and thereby mediates the association of irak with the receptor.	SIGNOR-67143
Q8IWL8	P00519	0	phosphorylation	up-regulates activity	0.2	STH interacts with tau and Abl, and Abl phosphorylates STH on its single tyrosine residue.	SIGNOR-279353
P15056	Q02750	1	phosphorylation	up-regulates activity	0.789	Activation of mek family kinases requires phosphorylation of two conserved ser/thr residueserine residues 218 and 222 of human mek1 are the primary sites for phosphorylation by c-raf.	SIGNOR-235475
P49841	Q13976	0	phosphorylation	down-regulates activity	0.26	Moreover, PrkG1 inhibits GSK3\u03b2 by binding and directly phosphorylating GSK3\u03b2 at its serine-9 residue (Zhao et al., xref ).\|Moreover, PrkG1 inhibits GSK3beta by binding and directly phosphorylating GSK3beta at its serine 9 residue.	SIGNOR-280094
Q9BXM7	P99999	1	null	down-regulates quantity	0.382	There is a strong cyto-protective role of PINK1 in maintaining mitochondrial homeostasis via different mechanisms. Overexpression of wild-type PINK1 in SH-SY5Y neuroblastoma cells stabilizes respiring mitochondrial networks through various mechanisms that include maintaining mitochondrial membrane potential, reducing basal and neurotoxin-induced ROS, suppression of cytochrome c release, reversal of toxin-induced fission, and suppression of autophagy	SIGNOR-249704
P23443	P08151	1	phosphorylation	up-regulates	0.523	In this study, we found that an activated mtor/s6k1 pathway promotes gli1 transcriptional activity and oncogenic function through s6k1-mediated gli1 phosphorylation at ser84, which releases gli1 from its endogenous inhibitor, sufu.	SIGNOR-196756
Q13188	P31749	0	phosphorylation	down-regulates	0.356	We determined that mst2 phosphorylation by akt limits mst2 activity in two ways: first, by blocking its binding to rassf1a and by promoting its association into the raf-1 inhibitory complex, and second, by preventing homodimerization of mst2, which is needed for its activation. we identified t117 and t384 as akt phosphorylation sites in mst2.	SIGNOR-163533
Q9Y6E7	P15336	0	transcriptional regulation	down-regulates quantity by repression	0.2	Our data suggest that mTORC1 promotes the binding of the E3 ligase, βTrCP, to CREB2 (Figure 4D), promoting CREB2 degradation by the proteasome (Figure 4E). Here, we show that mTORC1 promotes glutamine anaplerosis by activating glutamate dehydrogenase (GDH). This regulation requires transcriptional repression of SIRT4, the mitochondrial-localized sirtuin that inhibits GDH. Mechanistically, mTORC1 represses SIRT4 by promoting the proteasome-mediated destabilization of cAMP-responsive element binding 2 (CREB2).	SIGNOR-267831
P28482	P41182	1	phosphorylation	down-regulates	0.489	Here we show that antigen receptor activation leads to bcl-6 phosphorylation by mitogen-activated protein kinase (mapk). Phosphorylation, in turn, targets bcl-6 for rapid degradation by the ubiquitin/proteasome pathway.	SIGNOR-58481
O15055	P49674	0	phosphorylation	down-regulates quantity by destabilization	0.902	Priming-independent clusters located in the C-terminal portion of PER2’s PAS domains are targeted by CK1ε/δ and are required for ubiquitin ligase–mediated degradation of PER2	SIGNOR-277419
Q7Z6J0	P45983	2	binding	up-regulates	0.371	Posh activates jnk1 in cos-1 cells.	SIGNOR-55759
Q9HC98	Q13200	1	phosphorylation	up-regulates activity	0.2	Seven of these kinases (PIM1/2/3, MAP4K1/2, PKA, and NEK6) directly and robustly phosphorylated recombinant GST-Rpn1 at S361 in vitro (Fig. 3D and SI Appendix, Fig. S3 A and B).	SIGNOR-273894
Q06187	Q08881	2	phosphorylation	up-regulates	0.497	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 mechanismthe major phosphorylation sites were identified as conserved tyrosines, for itk y180	SIGNOR-98036
Q16513	O15530	0	phosphorylation	up-regulates	0.705	It is shown that activation in vitro and in vivo involves the activation loop phosphorylation of prk1/2 by 3-phosphoinositide-dependent protein kinase-1 (pdk1) /pdk1 phosphorylates the prks at their conserved activation loop threonines (thr-774 and thr-816 for prk1 and prk2, respectively)	SIGNOR-76710
P37231	P46934	0	ubiquitination	up-regulates activity	0.386	First, NEDD4 interacts with and ubiquitinates PPARgamma.\|NEDD4 increases PPARgamma stability through the inhibition of its proteasomal degradation.	SIGNOR-278540
Q13153	P49593	0	dephosphorylation	down-regulates activity	0.39	The p21-activated kinase PAK is negatively regulated by POPX1 and POPX2, a pair of serine/threonine phosphatases of the PP2C family\|POPX Can Dephosphorylate and Downregulate PAK\| To confirm that POPX2 acts on αPAK phospho-Thr422, a key regulator of activity in the kinase activation loop [9], we used phospho-specific antibodies against αPAK P-Thr422 (Figure 3B, lower panel), which proved to be an excellent substrate for POPX2. Similarly, complete loss of αPAK P-Ser57 with 0.2 μg POPX2 contrasts with the slight loss observed with 1.5 μg PP1. On the basis of these results, we suggest PAK is a substrate of POPX.	SIGNOR-248530
Q9UHD2	O95865	1	phosphorylation	down-regulates activity	0.2	TANK-binding kinase 1 (TBK1), a kinase downstream of MAVS, inhibited DDAH2 by phosphorylating DDAH2 at multiple sites. \|The T203D, T211D, S245D, and S253D mutations significantly reduced the inhibitory effect of DDAH2 on RLR signaling, suggesting that phosphorylation of these residues was critical for DDAH2 to inhibit activation o	SIGNOR-275648
O14757	P06493	0	phosphorylation	up-regulates	0.411	Chk1 itself is also subject to cdk-mediated phosphorylation at serines 286 and 301 (s286 and 301). We show that chk1 s301 phosphorylation increases as cells progress through s and g2 and that both cdk1 and cdk2 are likely to contribute to this modification in vivo. We also find that substitution of s286 and s301 with non-phosphorylatable alanine residues strongly attenuates dna damage-induced chk1 activation and g2 checkpoint proficiency	SIGNOR-175071
Q9UBF6	P67870	0	phosphorylation	up-regulates activity	0.329	In the present study, we show the evidence that CKBBP1 is phosphorylated on threonine residue at position 10 by CKII in vitro and in vivo. Most importantly, disruption of this phosphorylation in CKBBP1 results in accumulation of IκBα and p27Kip1 in HeLa cells and inhibits cell proliferation that appears to be linked to defects in G1/S transition.	SIGNOR-251081
P55211	P06493	0	phosphorylation	down-regulates	0.429	Here, we show that the apoptotic initiator protease caspase-9 is regulated during the cell cycle through periodic phosphorylation at an inhibitory site, thr125. This site is phosphorylated by cdk1/cyclin b1 during mitosis and in response to microtubule poisons that arrest cells at this stage of the cell cycle.	SIGNOR-141621
P35968	P35790	0	phosphorylation	down-regulates quantity by destabilization	0.249	Here, we show for the first time a possible mechanism by which CKI dependent phosphorylation of VEGFR2 at specific sites in its C-terminal tail triggers SCF beta-TRCP -mediated VEGFR2 ubiquitination and destruction.	SIGNOR-279029
P29350	P35968	1	dephosphorylation	down-regulates activity	0.668	Src homology 2 (SH2) domain containing protein tyrosine phosphatase-1 (SHP-1) dephosphorylates VEGF Receptor-2 and attenuates endothelial DNA synthesis, but not migration\|Knockdown of SHP-1 by siRNA or inhibition of c-Src by an inhibitor, results in augmented DNA synthesis perhaps due to increased phosphorylation of at least three tyrosine residues of KDR 996, 1059 and 1175	SIGNOR-248474
Q12809	Q96PU5	0	ubiquitination	down-regulates quantity by destabilization	0.399	As quantified in Fig. 5 B, only Nedd4-2 significantly increased the basal ubiquitylation of hERG1, while Nedd4-2-C801S and the other ubiquitin ligases had no effect.\|The major findings of this study are as follows : 1) hERG1 interacts via its PY motif with the ubiquitin ligase Nedd4-2, 2) this interaction promotes the down-regulation of the functional form of the channel at the plasma membrane through Nedd4-2 ubiquitylation of the channel, and 3) I hERG1 is strongly decreased by Nedd4-2 catalytic dependent activity.The hERG1 PY motif is a highly conserved sequence across animal species lines, highlighting its crucial role in the regulation of the hERG1 channel at the cell surface.	SIGNOR-278771
P21452	P08754	2	binding	up-regulates activity	0.2	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-256879
Q92890	Q8TAT6	2	binding	up-regulates activity	0.2	These findings ascribe specific functions to each of the components of the VCP-UFD1L-NPL4 complex in Vpu-mediated CD4 degradation: VCP energizes the process through ATP binding and hydrolysis, UFD1L binds ubiquitinated CD4 through recognition of K48 Ub chains, and NPL4 stabilizes UFD1L. VCP is thus likely to provide the energy required for extraction of CD4 from membranes.	SIGNOR-252422
P23508	Q13535	0	phosphorylation	up-regulates activity	0.2	MCC is phosphorylated at the ATM/ATR consensus sites Ser118 and Ser120. Finally, mutation of S118/120 to alanine did not affect MCC nuclear shuttling following UV but did impair MCC G2/M checkpoint activity.	SIGNOR-273514
Q04759	O15530	0	phosphorylation	up-regulates	0.572	We demonstrate that 3-phosphoinositide-dependent kinase 1 (pdk1) has an essential role in this pathway by regulating the activation of pkc and through signal-dependent recruiting of both pkc and card11 to lipid rafts.	SIGNOR-134869
P25090	P08754	2	binding	up-regulates activity	0.435	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-256745
P63092	P30550	2	binding	up-regulates activity	0.25	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 ‚â• -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 ‚â• -1.0 for defining true couplings. \| The score associated to this interaction has a LogRAi ‚â• -1.0.	SIGNOR-256774
Q14012	Q8N5S9	0	phosphorylation	up-regulates activity	0.414	Human calcium-calmodulin dependent protein kinase I: cDNA cloning, domain structure and activation by phosphorylation at threonine-177 by calcium-calmodulin dependent protein kinase I kinase.	SIGNOR-250717
P84243	P49336	0	phosphorylation	down-regulates activity	0.2	However, within T/G-Mediator, cdk8 phosphorylates serine-10 on histone H3, which in turn stimulates H3K14 acetylation by GCN5L within the complex. Tandem phosphoacetylation of H3 correlates with transcriptional activation, and ChIP assays demonstrate co-occupancy of T/G-Mediator components at several activated genes in vivo.	SIGNOR-273173
O00141	Q96J92	1	phosphorylation	up-regulates activity	0.415	In addition, we identified a novel SGK1 phosphorylation site (S1201) in WNK4, and phosphorylation at this site is reduced by Ca(2+)/CaM.	SIGNOR-276421
P98177	P11233	0	phosphorylation	up-regulates activity	0.2	We conclude that Ral-mediated phosphorylation of threonines 447 and 451 is required for proper activity of AFX-WT.	SIGNOR-249665
P67775	Q9Y243	1	dephosphorylation	down-regulates activity	0.738	Protein phosphatase 2A negatively regulates insulin's metabolic signaling pathway by inhibiting Akt (protein kinase B) activity in 3T3-L1 adipocytes	SIGNOR-248654
P42574	P49137	0	phosphorylation	up-regulates activity	0.311	MK2 Phosphorylates Caspase-3, Facilitates Nuclear Translocation of Caspase 3, and Regulates Apoptosis.\|Over-expression of MK2 led to an increase in nuclear caspase-3 activity.	SIGNOR-278960
Q99836	P14778	2	binding	up-regulates activity	0.945	Interleukin-1 (il-1) stimulates the association of the il-1 receptor-associated protein kinase (irak) with the heterodimer of il-iri and il-iracp via the adapter protein myd88.	SIGNOR-67140
Q99835	P63211	2	binding	up-regulates	0.2	Consistent with its predicted topology, smo couples to a specific family of inhibitory g protein (gis) to regulate hh signaling.	SIGNOR-148601
Q13433	P43403	0	phosphorylation	up-regulates activity	0.2	To summarize, upon TCR triggering Zap70 activates Zip6, which is localized to the IS, through phosphorylation of tyrosine residues likely located in the long cytoplasmic loop.\|Zip6 Is Phosphorylated by Zap70 in Response to TCR Stimulation.	SIGNOR-280165
Q8N165	Q05D32	0	dephosphorylation	up-regulates quantity by stabilization	0.356	We found that peptides corresponding to phosphoserines 194 and 216 of PDIK1L (S385 and S413 of STK35) were efficiently dephosphorylated by SCP4, whereas no activity was detected for the other two phosphopeptides (Figure 6D).	SIGNOR-273773
Q8TEW6	P07949	2	binding	up-regulates	0.576	We identified two new family members, dok-4 and dok-5, that can directly associate with y1062 of c-ret dok-4 and dok-5 enhance c-ret-dependent activation of mitogen-activated protein kinase	SIGNOR-109513
Q9BX84	P63244	2	binding	down-regulates activity	0.2	We identified RACK1 as the first TRPM6-associated protein and demonstrated that RACK1 inhibits TRPM6 channel activity depending on the phosphorylation state T1851 in the α-kinase domain.	SIGNOR-260921
P60953	Q96P48	0	gtpase-activating protein	down-regulates activity	0.531	We therefore developed a screening-compatible live-cell imaging assay, using FRET-based biosensors for the prototype GTPases RHOA, RAC1 and CDC4215,19,20 (Extended Data Fig. 2 and Supplementary Note 1)\|We found catalytic activities for 45/75 RhoGEFs and 48/63 RhoGAPs\| Our data thus not only reveal extensive promiscuity among regulators, but also that the inactivating RhoGAPs are less selective than the activating RhoGEFs (p-value=0.02)(Supplementary Table 2).	SIGNOR-260452
P19086	Q9HC97	2	binding	up-regulates activity	0.2	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-257112

Q15759

O75582

1

phosphorylation

up-regulates

0.615

Mitogen- and stress-activated protein kinase-1 (msk1) is directly activated by mapk and sapk2/p38, and may mediate activation of crebactivated by phosphorylation at ser-360, thr-581 and thr-700 by mapk1/erk2, mapk3/erk1 and mapk14/p38-alpha

SIGNOR-59443

P04637

P53778

0

phosphorylation

up-regulates activity

0.474

Furthermore, upon activation by oncogenic ras, p38gamma stimulated the transcriptional activity of p53 by phosphorylating p53 at Ser(33), suggesting that the ability of p38gamma to mediate senescence is at least partly achieved through p53.

SIGNOR-280026

O15111

O14920

1

phosphorylation

up-regulates activity

0.67

Our data indicate that IKKα stimulates IKKβ kinase activity for the IκBα substrate. Finally, we demonstrate that IKKα can phosphorylate IKKβ in in vitro kinase assays.

SIGNOR-250772

Q99835

Q9UBI6

2

binding

up-regulates

0.2

As pka suppresses the activity of gli, smo might use the stimulation of pi3k by galfai and gbetagamma subu- nits to block pka in cells that have high levels of camp.

SIGNOR-152817

P01106

P50750

0

phosphorylation

down-regulates activity

0.54

CDK9 promotes phosphorylation of MYC on Ser 62 .

SIGNOR-279024

P05129

P06127

1

phosphorylation

up-regulates

0.341

Cd5 is a good pkc substrate. Phosphorylation of cd5 is necessary for cd5-mediated lipid second messenger generation.

SIGNOR-85183

P43405

Q9GZY6

1

phosphorylation

up-regulates activity

0.592

Our results indicated that human LAB was primarily phosphorylated on three membrane-distal tyrosines, Tyr(136), Tyr(193), and Tyr(233). Mutation of these three tyrosines abolished Grb2 binding and LAB function. Our data suggested that these tyrosines are the most important tyrosines for LAB function.The dramatic reduction in phosphorylation of the LAB Y233F mutant suggested that Tyr233 is a primary target of the Syk family kinases.

SIGNOR-273576

P49841

P04198

1

phosphorylation

down-regulates quantity by destabilization

0.33

Because GSK3\u03b2 phosphorylates Nmyc at T58, we assessed GSK3\u03b2 activation in Dex-treated MB cells.

SIGNOR-279722

P38405

O00254

2

binding

up-regulates activity

0.2

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-256904

P06493

Q8NHV4

1

phosphorylation

up-regulates activity

0.585

Here we report that the function of Nedd1 is regulated by Cdk1 and Plk1. During mitosis, Nedd1 is firstly phosphorylated at T550 by Cdk1, which creates a binding site for the polo-box domain of Plk1. Then, Nedd1 is further phosphorylated by Plk1 at four sites: T382, S397, S637 and S426. The sequential phosphorylation of Nedd1 by Cdk1 and Plk1 promotes its interaction with gamma-tubulin for targeting the gammaTuRC to the centrosome and is important for spindle formation.

SIGNOR-272973

O00429

P00519

0

phosphorylation

up-regulates activity

0.26

In this study, we found that c-Abl phosphorylated Drp1 at tyrosine 266, 368 and 449 in vitro and in vivo, which augmented the GTPase activity of Drp1 and promoted Drp1-mediated mitochondrial fragmentation.

SIGNOR-277328

P04637

Q92630

0

phosphorylation

up-regulates

0.67

Here, we demonstrate that the dual-specificity tyrosine-phosphorylation-regulated kinase 2 (dyrk2) directly phosphorylates p53 at ser46. these findings indicate that dyrk2 regulates p53 to induce apoptosis in response to dna damage.

SIGNOR-153544

Q92847

Q9UBU3

2

binding

up-regulates

0.722

In contrast to wild-type mice, acute treatment of ghsr- mice with ghrelin stimulated neither gh release nor food intake, showing that the ghsr is a biologically relevant ghrelin receptor.

SIGNOR-123948

Q14444

Q13283

2

binding

up-regulates activity

0.588

Caprin-1 and G3BP-1 were directly or indirectly associated in a stable complex. The Caprin-1/G3BP-1 complex occurs in cytoplasmic RNA granules

SIGNOR-260982

P11831

P78527

0

phosphorylation

up-regulates activity

0.406

The carboxyl-terminal transcription activation domain was mapped within a 71-amino acid region that contains both DNA-PK phosphorylation sites. Amino acid substitutions that interfered with phosphorylation by DNA-PK at Ser-435/446 in GAL4-SRF fusion proteins were reduced in transactivation potency. From these data we suggest that DNA-PK phosphorylation may modulate SRF activity in vivo.

SIGNOR-248922

P27361

P10636-2

1

phosphorylation

down-regulates activity

0.501

We have studied the relationship between the phosphorylation oftau by several kinases (MARK, PKA, MAPK, GSK3) and its assembly into PHFs. By contrast, MARK and PKA phosphorylate several sites within the repeats (notably theKXGS motifs including Ser262, Ser324, and Ser356, plus Ser320); in addition PKA phosphorylates somesites in the flanking domains, notably Ser214. This type of phosphorylation strongly reduces tau’s affinityfor microtubules, and at the same time inhibits tau’s assembly into PHFs.

SIGNOR-275434

P18846

O75676

0

phosphorylation

up-regulates

0.615

Msk1 and msk2 directly phosphorilate and activate transcription factors such as creb1, atf1.

SIGNOR-116252

O15303

P63092

2

binding

up-regulates activity

0.34

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-264084

P0DP25

P29474

2

binding

up-regulates activity

0.565

Electrons flow from the C-terminal reductase domain of one NOS monomer to the N-terminal oxygenase domain of the other NOS monomer (Siddhanta et al., 1998). The primary mode of enzyme activation is the binding of calcium-bound calmodulin to the N-terminal CaM-binding domain. This facilitates a structure change and the flow of electrons from NADPH through the flavins to the oxygenase domain of the other eNOS monomer

SIGNOR-266339

Q53GL7

Q13283

1

post translational modification

up-regulates activity

0.2

Further, we pinpoint the core SG component, G3BP1, as a PARP10 substrate and find that PARP10 regulates SG assembly driven by both G3BP1 and its modeled mechanism. Intriguingly, while PARP10 only adds a single ADP-ribose unit to proteins, G3BP1 is PARylated, suggesting its potential role as a scaffold for protein recruitment. PARP10 knockdown alters the SG core composition, notably decreasing translation factor presence.

SIGNOR-273727

Q96GD4

Q53HL2

1

phosphorylation

up-regulates activity

0.82

AURKB directly phosphorylated CDCA8 at Ser(154), Ser(219), Ser(275), and Thr(278) and seemed to stabilize CDCA8 protein in cancer cells.|Phosphorylation and activation of cell division cycle associated 8 by aurora kinase B plays a significant role in human lung carcinogenesis.

SIGNOR-279506

Q8NB16

P30530

0

phosphorylation

up-regulates quantity by stabilization

0.2

TAM kinases phosphorylate MLKL to promote necroptosis. MLKL is then recruited to the plasma membrane, where TAM kinases phosphorylate MLKL at Tyr376 (Figure 5G, step 5), promoting its oligomerization and formation of membrane-rupturing pores that result in necrotic cell death (Figure 5G, step 6).

SIGNOR-274119

Q05901

O00468

2

binding

up-regulates activity

0.2

Treatment of muscle cells with neural agrin causes tyrosine phosphorylation of the AChR β subunit and induces AChR clustering by promoting anchoring of the receptor protein to postsynaptic cytoskeleton. Regulation of acetylcholine receptor clustering by the tumor suppressor APC. By showing a direct requirement for APC in AChR clustering, our present study suggests that the Wnt/β-catenin pathway may crosstalk with the agrin signaling cascade during the formation of mammalian neuromuscular junction.

SIGNOR-264260

P00533

Q13332

0

dephosphorylation

down-regulates activity

0.43

Similarly, Pestana et al. (89) have reported that overexpression of RPTPsigma in human A431 carcinoma cells partially inhibits EGFR activation, whereas antisense mediated suppression of RPTPsigma expression enhances EGFR activation, substrate phosphorylation, and signalling.|These data indicate that LAR and RPTPsigma may have a significant role in GPCR induced EGFR signalling.Whereas in A431 cells LAR and RPTPsigma may act to suppress the EGFR in response to GPCR activation, it is possible that the converse may also be true in other cell types.

SIGNOR-277145

Q8IVH8

Q13233

1

phosphorylation

up-regulates

0.453

With regard to at least mekk1, serine/threonine kinases such as nik,glkand hpk1 appear also to be important for regulation

SIGNOR-61814

P25116

P63096

2

binding

up-regulates

0.402

Upon proteolysis, the newly formed n terminus acts as a tethered ligand that activates the receptor and initiates signaling cascades through multiple g proteins (galfaq, galfai, and galfa12/13).

SIGNOR-196009

Q13829

Q13618

2

binding

up-regulates activity

0.461

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-264232

Q15054

P17612

0

phosphorylation

down-regulates

0.2

In this study, we identified s458, located in the pcna-interacting protein (pip-box) motif of p68, as a phosphorylation site for pka. Phosphomimetic mutation of s458 resulted in a decrease in p68 affinity for pcna as well as the processivity of pol _.

SIGNOR-195203

Q02156

P17302

1

phosphorylation

down-regulates activity

0.44

Phosphorylation of connexin43 on serine368 by protein kinase C regulates gap junctional communication.|These data strongly suggest that PKC directly phosphorylates Cx43 on S368 in vivo, which results in a change in single channel behavior that contributes to a decrease in intercellular communication.

SIGNOR-144465

Q14114

P06241

0

phosphorylation

up-regulates quantity

0.635

Fyn phosphorylates ApoER2.|Together these data demonstrate that Fyn activity is necessary for its effects increasing ApoER2 levels.

SIGNOR-278197

P27361

O95997

1

phosphorylation

up-regulates

0.304

Pttg is phosphorylated in vitro on ser(162) by map kinase and this phosphorylation site plays an essential role in pttg transactivation function.

SIGNOR-79519

Q96GD4

Q9P2J3

2

binding

up-regulates activity

0.71

Aurora B Interacts with the Cul3 Complex during Mitosis and Is Ubiquitylated in a Cul3-Dependent Manner In Vivo and In Vitro. our results suggest that Cul3/KLHL9/KLHL13 activity is required to remove the chromosomal passenger protein Aurora B from mitotic chromosomes, and that Aurora B is ubiquitylated in vivo and in vitro in a KLHL9/13-dependent manner. We conclude that the Cul3/KLHL9/KLHL13 E3 ligase is an important cell-cycle regulator which, in addition to the anaphase-promoting complex (APC), coordinates mitotic progression and completion of cytokinesis.

SIGNOR-271658

P12931

P04637

1

phosphorylation

down-regulates quantity by destabilization

0.524

We recently found that ISGylation of the p53 tumor suppressor is an important novel mechanism to control its stability. Here we identified that Isg15-dependent regulation of p53 can be enhanced by different oncogenes. We further show that the Src-mediated phosphorylation of p53 on Tyr126 and Tyr220 has a positive effect on p53 ISGylation by enhancing Herc5 binding.

SIGNOR-276668

Q15796

Q13233

0

phosphorylation

up-regulates activity

0.474

As yet, the apparent discrepancy between these and above data is not clear, but obviously the type of cell under study and the cellular context may play an important role.In endothelial cells, Smad2 activity is stimulated by MEKK1, a component of the Stress Activated Protein Kinase and c-Jun N terminal kinase (SAPK and JNK) pathway.|Phosphorylation of Smad2 by MEKK1 increased its association with Smad4, its nuclear accumulation and its transcription induction activity .

SIGNOR-279064

P19474

Q13501

1

ubiquitination

down-regulates activity

0.404

TRIM21 directly ubiquitylates p62 at residue K7 to inhibit its oligomerization and sequestration function.|TRIM21 negatively regulates p62 mediated sequestration of Keap1 and antioxidant response.

SIGNOR-278602

P49116

Q86VZ6

2

binding

down-regulates

0.453

Tip27 interacts specifically with tak1 / tip27 functions as a tak1-selective repressor

SIGNOR-127900

Q9UKB1

Q9HAW4

1

ubiquitination

down-regulates

0.345

Claspin degradation was triggered by its interaction with, and ubiquitylation by, the scfbetatrcp ubiquitin ligase.

SIGNOR-148438

Q9NXA8

P11413

1

catalytic activity

up-regulates activity

0.278

Here, we report that SIRT5 desuccinylates and deglutarylates isocitrate dehydrogenase 2 (IDH2) and glucose-6-phosphate dehydrogenase (G6PD), respectively, and thus activates both NADPH-producing enzymes.

SIGNOR-261211

Q9NXV6

Q00987

0

ubiquitination

down-regulates

0.37

Carf interacts with hdm2 and is ubiquitinated and negatively regulated by hdm2 by proteasome-dependent degradation.

SIGNOR-160974

Q93098

O75581

2

binding

up-regulates

0.617

Wnt proteins bind to the frizzled receptors and lrp5/6 co-receptors, and through stabilizing the critical mediator betBeta-catenin, initiate a complex signaling cascade that plays an important role in regulating cell proliferation and differentiation.

SIGNOR-132027

P07947

P46937

1

phosphorylation

up-regulates activity

0.721

Yes directly phosphorylates YAP and TAZ, resulting in their increased nuclear localization and transcriptional activity.Analysis by mass spectrometry identified Tyr391 and Tyr407 as the two phosphorylation sites of YAP, whereas Tyr305 was the sole phosphorylated residue of TAZ (Fig. 5F and fig. S4, A to C).

SIGNOR-277653

O60566

O14757

0

phosphorylation

up-regulates activity

0.447

Nonetheless, in our experimental system a Chk1-dependent BubR1 phosphorylation was also observed after Noc treatment.|Possible requirement of Chk1 in U2OS cells to activate the mitotic spindle checkpoint proteins Mad2 and BubR1.

SIGNOR-280223

P04406

Q5XX13

0

polyubiquitination

up-regulates activity

0.2

Mechanistically, FBXW10 promotes GAPDH polyubiquitination and activation; VRK2-dependent phosphorylation of GAPDH Ser151 residue is critical for GAPDH ubiquitination and activation.

SIGNOR-277841

P25963

Q14164

0

phosphorylation

down-regulates quantity by destabilization

0.484

The activated ikk complex then phosphorylates ikbalfa (an inhibitor of nf-kb) thereby targeting it for ubiquitination and proteasomal degradation.

SIGNOR-167524

P16104

O76064

0

ubiquitination

up-regulates

0.2

Rnf8 can ubiquitylate histone h2a and h2ax,

SIGNOR-159309

P68363

Q8NG68

0

tyrosination

down-regulates

0.46

Tubulin tyrosine ligase (ttl) adds a c-terminal tyr to __tubulin as part of a tyrosination/detyrosination cycle present in most eukaryotic cells. / ttl inhibits spontaneous tubulin polymerization

SIGNOR-176915

P06241

P35222

1

phosphorylation

down-regulates activity

0.851

Interaction of beta-catenin with alpha-catenin is regulated by the phosphorylation of beta-catenin Tyr-142. This residue can be phosphorylated in vitro by Fer or Fyn tyrosine kinases. Transfection of these kinases to epithelial cells disrupted the association between both catenins.

SIGNOR-251162

Q13485

P28482

0

phosphorylation

up-regulates

0.511

Phosphorylation of thr276 is shown to be important for tgf-?-Induced nuclear accumulation and, as a consequence, transcriptional activity of smad4. these results suggest that smad4 can be phosphorylated by erk2 at thr276.

SIGNOR-101660

P62826

O43592

2

binding

up-regulates activity

0.815

The first step in export appears to be the formation of a trimeric tRNA/exportin-t/RanGTP complex. tRNA and RanGTP bind to exportin-t in a highly cooperative manner: tRNA increases the affinity of exportin-t for RanGTP apparently 300-fold (Figure 5A); conversely, RanGTP has to increase the affinity of exportin-t for tRNA by the same factor. RanGTP appears to have at least two functions in this complex. First, it stabilizes the tRNA/exportin-t interaction (see Figure 4B). Second, exportin-t apparently has to bind RanGTP for rapid exit from the nucleus

SIGNOR-261392

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

P55210

Q13177

0

phosphorylation

down-regulates

0.351

Pak2 can bind with caspase-7 and phosphorylate caspase-7 at the ser-30, thr-173, and ser-239 sites. Functionally, the phosphorylation of caspase-7 decreases its activity, thereby inhibiting cellular apoptosis.

SIGNOR-173655

O43303

Q12798

2

binding

up-regulates activity

0.483

We report that CP110 interacts with two different Ca2+-binding proteins, calmodulin (CaM) and centrin, in vivo. our data demonstrate a functional role for CaM binding to CP110 and suggest that CP110 cooperates with CaM and centrin to regulate progression through cytokinesis.

SIGNOR-265966

P00519

Q92466

1

phosphorylation

down-regulates

0.458

C-abl might act as a negative regulator of uv-ddb by phosphorylating ddb2

SIGNOR-90446

O75444

P35452

2

binding

down-regulates activity

0.367

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

SIGNOR-221887

Q9UQ26

P20336

1

relocalization

up-regulates activity

0.762

N-terminal interactions of RIMs with RAB3 and MUNC13 regulate DCV fusion. Through N-terminal interactions, RIMs position MUNC13 and recruit DCVs via RAB3, which is located on the vesicle

SIGNOR-264377

P11802

Q06413

2

binding

down-regulates

0.283

In contrast to cdk2, cyclin d/cdk4 blocks myod activity through an as yet unclear mechanism that may involve direct binding. Cyclin d/cdk4 can also block the activity of myogenin and all mef2 isoforms.

SIGNOR-176518

P01111

P42338

2

binding

up-regulates

0.668

Grb2 binds and activates sos, which then activates ras, and this activates p110 independently of p85./it was also described that ras interacts with pi3k in a direct manner./lysine residue 227 is essential for the interaction of ras with pi3k

SIGNOR-175225

P51617

Q99836

2

binding

up-regulates activity

0.848

Interleukin-1 (il-1) stimulates the association of the il-1 receptor-associated protein kinase (irak) with the heterodimer of il-iri and il-iracp via the adapter protein myd88. Myd88 binds to both irak (il-1 receptor-associated kinase) and the heterocomplex (the signaling complex) of the two receptor chains and thereby mediates the association of irak with the receptor.

SIGNOR-67143

Q8IWL8

P00519

0

phosphorylation

up-regulates activity

0.2

STH interacts with tau and Abl, and Abl phosphorylates STH on its single tyrosine residue.

SIGNOR-279353

P15056

Q02750

1

phosphorylation

up-regulates activity

0.789

Activation of mek family kinases requires phosphorylation of two conserved ser/thr residueserine residues 218 and 222 of human mek1 are the primary sites for phosphorylation by c-raf.

SIGNOR-235475

P49841

Q13976

0

phosphorylation

down-regulates activity

0.26

Moreover, PrkG1 inhibits GSK3\u03b2 by binding and directly phosphorylating GSK3\u03b2 at its serine-9 residue (Zhao et al., xref ).|Moreover, PrkG1 inhibits GSK3beta by binding and directly phosphorylating GSK3beta at its serine 9 residue.

SIGNOR-280094

Q9BXM7

P99999

1

null

down-regulates quantity

0.382

There is a strong cyto-protective role of PINK1 in maintaining mitochondrial homeostasis via different mechanisms. Overexpression of wild-type PINK1 in SH-SY5Y neuroblastoma cells stabilizes respiring mitochondrial networks through various mechanisms that include maintaining mitochondrial membrane potential, reducing basal and neurotoxin-induced ROS, suppression of cytochrome c release, reversal of toxin-induced fission, and suppression of autophagy

SIGNOR-249704

P23443

P08151

1

phosphorylation

up-regulates

0.523

In this study, we found that an activated mtor/s6k1 pathway promotes gli1 transcriptional activity and oncogenic function through s6k1-mediated gli1 phosphorylation at ser84, which releases gli1 from its endogenous inhibitor, sufu.

SIGNOR-196756

Q13188

P31749

0

phosphorylation

down-regulates

0.356

We determined that mst2 phosphorylation by akt limits mst2 activity in two ways: first, by blocking its binding to rassf1a and by promoting its association into the raf-1 inhibitory complex, and second, by preventing homodimerization of mst2, which is needed for its activation. we identified t117 and t384 as akt phosphorylation sites in mst2.

SIGNOR-163533

Q9Y6E7

P15336

0

transcriptional regulation

down-regulates quantity by repression

0.2

Our data suggest that mTORC1 promotes the binding of the E3 ligase, βTrCP, to CREB2 (Figure 4D), promoting CREB2 degradation by the proteasome (Figure 4E). Here, we show that mTORC1 promotes glutamine anaplerosis by activating glutamate dehydrogenase (GDH). This regulation requires transcriptional repression of SIRT4, the mitochondrial-localized sirtuin that inhibits GDH. Mechanistically, mTORC1 represses SIRT4 by promoting the proteasome-mediated destabilization of cAMP-responsive element binding 2 (CREB2).

SIGNOR-267831

P28482

P41182

1

phosphorylation

down-regulates

0.489

Here we show that antigen receptor activation leads to bcl-6 phosphorylation by mitogen-activated protein kinase (mapk). Phosphorylation, in turn, targets bcl-6 for rapid degradation by the ubiquitin/proteasome pathway.

SIGNOR-58481

O15055

P49674

0

phosphorylation

down-regulates quantity by destabilization

0.902

Priming-independent clusters located in the C-terminal portion of PER2’s PAS domains are targeted by CK1ε/δ and are required for ubiquitin ligase–mediated degradation of PER2

SIGNOR-277419

Q7Z6J0

P45983

2

binding

up-regulates

0.371

Posh activates jnk1 in cos-1 cells.

SIGNOR-55759

Q9HC98

Q13200

1

phosphorylation

up-regulates activity

0.2

Seven of these kinases (PIM1/2/3, MAP4K1/2, PKA, and NEK6) directly and robustly phosphorylated recombinant GST-Rpn1 at S361 in vitro (Fig. 3D and SI Appendix, Fig. S3 A and B).

SIGNOR-273894

Q06187

Q08881

2

phosphorylation

up-regulates

0.497

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 mechanismthe major phosphorylation sites were identified as conserved tyrosines, for itk y180

SIGNOR-98036

Q16513

O15530

0

phosphorylation

up-regulates

0.705

It is shown that activation in vitro and in vivo involves the activation loop phosphorylation of prk1/2 by 3-phosphoinositide-dependent protein kinase-1 (pdk1) /pdk1 phosphorylates the prks at their conserved activation loop threonines (thr-774 and thr-816 for prk1 and prk2, respectively)

SIGNOR-76710

P37231

P46934

0

ubiquitination

up-regulates activity

0.386

First, NEDD4 interacts with and ubiquitinates PPARgamma.|NEDD4 increases PPARgamma stability through the inhibition of its proteasomal degradation.

SIGNOR-278540

Q13153

P49593

0

dephosphorylation

down-regulates activity

0.39

The p21-activated kinase PAK is negatively regulated by POPX1 and POPX2, a pair of serine/threonine phosphatases of the PP2C family|POPX Can Dephosphorylate and Downregulate PAK| To confirm that POPX2 acts on αPAK phospho-Thr422, a key regulator of activity in the kinase activation loop [9], we used phospho-specific antibodies against αPAK P-Thr422 (Figure 3B, lower panel), which proved to be an excellent substrate for POPX2. Similarly, complete loss of αPAK P-Ser57 with 0.2 μg POPX2 contrasts with the slight loss observed with 1.5 μg PP1. On the basis of these results, we suggest PAK is a substrate of POPX.

SIGNOR-248530

Q9UHD2

O95865

1

phosphorylation

down-regulates activity

0.2

TANK-binding kinase 1 (TBK1), a kinase downstream of MAVS, inhibited DDAH2 by phosphorylating DDAH2 at multiple sites. |The T203D, T211D, S245D, and S253D mutations significantly reduced the inhibitory effect of DDAH2 on RLR signaling, suggesting that phosphorylation of these residues was critical for DDAH2 to inhibit activation o

SIGNOR-275648

O14757

P06493

0

phosphorylation

up-regulates

0.411

Chk1 itself is also subject to cdk-mediated phosphorylation at serines 286 and 301 (s286 and 301). We show that chk1 s301 phosphorylation increases as cells progress through s and g2 and that both cdk1 and cdk2 are likely to contribute to this modification in vivo. We also find that substitution of s286 and s301 with non-phosphorylatable alanine residues strongly attenuates dna damage-induced chk1 activation and g2 checkpoint proficiency

SIGNOR-175071

Q9UBF6

P67870

0

phosphorylation

up-regulates activity

0.329

In the present study, we show the evidence that CKBBP1 is phosphorylated on threonine residue at position 10 by CKII in vitro and in vivo. Most importantly, disruption of this phosphorylation in CKBBP1 results in accumulation of IκBα and p27Kip1 in HeLa cells and inhibits cell proliferation that appears to be linked to defects in G1/S transition.

SIGNOR-251081

P55211

P06493

0

phosphorylation

down-regulates

0.429

Here, we show that the apoptotic initiator protease caspase-9 is regulated during the cell cycle through periodic phosphorylation at an inhibitory site, thr125. This site is phosphorylated by cdk1/cyclin b1 during mitosis and in response to microtubule poisons that arrest cells at this stage of the cell cycle.

SIGNOR-141621

P35968

P35790

0

phosphorylation

down-regulates quantity by destabilization

0.249

Here, we show for the first time a possible mechanism by which CKI dependent phosphorylation of VEGFR2 at specific sites in its C-terminal tail triggers SCF beta-TRCP -mediated VEGFR2 ubiquitination and destruction.

SIGNOR-279029

P29350

P35968

1

dephosphorylation

down-regulates activity

0.668

Src homology 2 (SH2) domain containing protein tyrosine phosphatase-1 (SHP-1) dephosphorylates VEGF Receptor-2 and attenuates endothelial DNA synthesis, but not migration|Knockdown of SHP-1 by siRNA or inhibition of c-Src by an inhibitor, results in augmented DNA synthesis perhaps due to increased phosphorylation of at least three tyrosine residues of KDR 996, 1059 and 1175

SIGNOR-248474

Q12809

Q96PU5

0

ubiquitination

down-regulates quantity by destabilization

0.399

As quantified in Fig. 5 B, only Nedd4-2 significantly increased the basal ubiquitylation of hERG1, while Nedd4-2-C801S and the other ubiquitin ligases had no effect.|The major findings of this study are as follows : 1) hERG1 interacts via its PY motif with the ubiquitin ligase Nedd4-2, 2) this interaction promotes the down-regulation of the functional form of the channel at the plasma membrane through Nedd4-2 ubiquitylation of the channel, and 3) I hERG1 is strongly decreased by Nedd4-2 catalytic dependent activity.The hERG1 PY motif is a highly conserved sequence across animal species lines, highlighting its crucial role in the regulation of the hERG1 channel at the cell surface.

SIGNOR-278771

P21452

P08754

2

binding

up-regulates activity

0.2

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-256879

Q92890

Q8TAT6

2

binding

up-regulates activity

0.2

These findings ascribe specific functions to each of the components of the VCP-UFD1L-NPL4 complex in Vpu-mediated CD4 degradation: VCP energizes the process through ATP binding and hydrolysis, UFD1L binds ubiquitinated CD4 through recognition of K48 Ub chains, and NPL4 stabilizes UFD1L. VCP is thus likely to provide the energy required for extraction of CD4 from membranes.

SIGNOR-252422

P23508

Q13535

0

phosphorylation

up-regulates activity

0.2

MCC is phosphorylated at the ATM/ATR consensus sites Ser118 and Ser120. Finally, mutation of S118/120 to alanine did not affect MCC nuclear shuttling following UV but did impair MCC G2/M checkpoint activity.

SIGNOR-273514

Q04759

O15530

0

phosphorylation

up-regulates

0.572

We demonstrate that 3-phosphoinositide-dependent kinase 1 (pdk1) has an essential role in this pathway by regulating the activation of pkc and through signal-dependent recruiting of both pkc and card11 to lipid rafts.

SIGNOR-134869

P25090

P08754

2

binding

up-regulates activity

0.435

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-256745

P63092

P30550

2

binding

up-regulates activity

0.25

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 ‚â• -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 ‚â• -1.0 for defining true couplings. | The score associated to this interaction has a LogRAi ‚â• -1.0.

SIGNOR-256774

Q14012

Q8N5S9

0

phosphorylation

up-regulates activity

0.414

Human calcium-calmodulin dependent protein kinase I: cDNA cloning, domain structure and activation by phosphorylation at threonine-177 by calcium-calmodulin dependent protein kinase I kinase.

SIGNOR-250717

P84243

P49336

0

phosphorylation

down-regulates activity

0.2

However, within T/G-Mediator, cdk8 phosphorylates serine-10 on histone H3, which in turn stimulates H3K14 acetylation by GCN5L within the complex. Tandem phosphoacetylation of H3 correlates with transcriptional activation, and ChIP assays demonstrate co-occupancy of T/G-Mediator components at several activated genes in vivo.

SIGNOR-273173

O00141

Q96J92

1

phosphorylation

up-regulates activity

0.415

In addition, we identified a novel SGK1 phosphorylation site (S1201) in WNK4, and phosphorylation at this site is reduced by Ca(2+)/CaM.

SIGNOR-276421

P98177

P11233

0

phosphorylation

up-regulates activity

0.2

We conclude that Ral-mediated phosphorylation of threonines 447 and 451 is required for proper activity of AFX-WT.

SIGNOR-249665

P67775

Q9Y243

1

dephosphorylation

down-regulates activity

0.738

Protein phosphatase 2A negatively regulates insulin's metabolic signaling pathway by inhibiting Akt (protein kinase B) activity in 3T3-L1 adipocytes

SIGNOR-248654

P42574

P49137

0

phosphorylation

up-regulates activity

0.311

MK2 Phosphorylates Caspase-3, Facilitates Nuclear Translocation of Caspase 3, and Regulates Apoptosis.|Over-expression of MK2 led to an increase in nuclear caspase-3 activity.

SIGNOR-278960

Q99836

P14778

2

binding

up-regulates activity

0.945

Interleukin-1 (il-1) stimulates the association of the il-1 receptor-associated protein kinase (irak) with the heterodimer of il-iri and il-iracp via the adapter protein myd88.

SIGNOR-67140

Q99835

P63211

2

binding

up-regulates

0.2

Consistent with its predicted topology, smo couples to a specific family of inhibitory g protein (gis) to regulate hh signaling.

SIGNOR-148601

Q13433

P43403

0

phosphorylation

up-regulates activity

0.2

To summarize, upon TCR triggering Zap70 activates Zip6, which is localized to the IS, through phosphorylation of tyrosine residues likely located in the long cytoplasmic loop.|Zip6 Is Phosphorylated by Zap70 in Response to TCR Stimulation.

SIGNOR-280165

Q8N165

Q05D32

0

dephosphorylation

up-regulates quantity by stabilization

0.356

We found that peptides corresponding to phosphoserines 194 and 216 of PDIK1L (S385 and S413 of STK35) were efficiently dephosphorylated by SCP4, whereas no activity was detected for the other two phosphopeptides (Figure 6D).

SIGNOR-273773

Q8TEW6

P07949

2

binding

up-regulates

0.576

We identified two new family members, dok-4 and dok-5, that can directly associate with y1062 of c-ret dok-4 and dok-5 enhance c-ret-dependent activation of mitogen-activated protein kinase

SIGNOR-109513

Q9BX84

P63244

2

binding

down-regulates activity

0.2

We identified RACK1 as the first TRPM6-associated protein and demonstrated that RACK1 inhibits TRPM6 channel activity depending on the phosphorylation state T1851 in the α-kinase domain.

SIGNOR-260921

P60953

Q96P48

0

gtpase-activating protein

down-regulates activity

0.531

We therefore developed a screening-compatible live-cell imaging assay, using FRET-based biosensors for the prototype GTPases RHOA, RAC1 and CDC4215,19,20 (Extended Data Fig. 2 and Supplementary Note 1)|We found catalytic activities for 45/75 RhoGEFs and 48/63 RhoGAPs| Our data thus not only reveal extensive promiscuity among regulators, but also that the inactivating RhoGAPs are less selective than the activating RhoGEFs (p-value=0.02)(Supplementary Table 2).

SIGNOR-260452

P19086

Q9HC97

2

binding

up-regulates activity

0.2

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-257112