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
P19086	Q99500	2	binding	up-regulates activity	0.385	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-257330
P17612	Q07343	1	phosphorylation	up-regulates activity	0.605	PKA-mediated phosphorylation of Ser-56 in UCR1 of PDE4B4 leads to activation of this long isoform	SIGNOR-250024
Q14896	Q05655	0	phosphorylation	up-regulates	0.2	The triple aspartic acid mutation shows greater distance between the two thick myosin filaments (affects the steric arrangement of the filament distances) in heart tissue. Mutation is cardioprotective during stress (ischemia-reprofusion injury) against apoptosis similar to isoproterenol treatment.	SIGNOR-150355
P43694	P11802	0	phosphorylation	up-regulates activity	0.356	In addition, we have shown that CDK4 can enhance cardiogenic activity of GATA4 (XREF_FIG).\|The physical and functional interactions between GATA4 and Cyclin D2 depend on phosphorylation of Ser 160 of GATA4, which can be mediated in vitro by CDK4.	SIGNOR-279148
Q99683	P46734	1	phosphorylation	up-regulates activity	0.599	Ask1 is a member of a mapkkk family and functions as an upstream kinase engaged in c-jun nh2-terminal kinase (jnk)/p38 signaling via the phosphorylation and activation of mapkks, such as mkk3, -4, -6, and -7	SIGNOR-161763
P12931	P24666	0	dephosphorylation	up-regulates activity	0.438	LMWPTP dephosphorylated pY(527)-Src and pY(416)-Src in vitro, with greater specificity for pY(527)Src. Activation of LMWPTP produced strong activation of Src mediated by fast dephosphorylation of pY(527)-Src, followed by slower deactivation of this kinase via dephosphorylation of pY(416)Src.	SIGNOR-248454
P50750	Q15596	1	phosphorylation	up-regulates activity	0.246	Interestingly, GRIP1 is phosphorylated at an N-terminal serine cluster by cyclin-dependent kinase-9 (CDK9), which is recruited into GC-induced GR:GRIP1:CDK9 hetero-complexes, producing distinct GRE-specific GRIP1 phospho-isoforms. Phosphorylation potentiates GRIP1 coactivator but, remarkably, not its corepressor properties.	SIGNOR-256098
O95837	P30559	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-257332
Q14643	Q9BS26	2	binding	down-regulates activity	0.58	In this study, we found that ERp44, an ER lumenal protein of the thioredoxin family, directly interacts with the third lumenal loop of IP(3)R type 1 (IP(3)R1) and that the interaction is dependent on pH, Ca(2+) concentration, and redox state. In this study we demonstrated that ERp44 directly interacts with the L3V domain of IP3R1, thereby inhibiting its channel activity.	SIGNOR-261046
Q14164	P35813	0	dephosphorylation	down-regulates activity	0.279	PPM1A directly dephosphorylates both MAVS and TBK1 and IKKepsilon.\|In a similar in vitro phosphatase assay, incubation of PPM1A also eliminated TBK1 and IKKepsilon phosphorylation at Ser 172 residue, evidenced by phospho-S172 immunoblotting (XREF_FIG, F and G).\|These observations suggest that PPM1A may block kinase activities of TBK1 and IKKepsilon.	SIGNOR-277072
Q9BTC0	P08648	1	transcriptional regulation	up-regulates quantity by expression	0.2	Dido1 upregulates the expression of Integrin αV, thereby influencing the attachment, apoptosis and migration of melanoma cells.	SIGNOR-261580
P36873	P51955	0	phosphorylation	down-regulates	0.488	Pp1 is a substrate for nek2 and phosphorylation of pp1gamma(1) on two c-terminal sites reduces its phosphatase activity.	SIGNOR-78603
Q9BZR9	O43318	1	polyubiquitination	up-regulates activity	0.343	These results suggest that TRIM8 could mediate K63-linked polyubiquitination of TAK1 at residue K158.These results suggest that TRIM8 is involved in TNFα- and IL-1β–induced NF-κB activation by mediating K63-linked TAK1 polyubiquitination and subsequent activation.	SIGNOR-271890
Q14493	Q96A08	1	translation regulation	up-regulates quantity by expression	0.2	Synthesis of mature histone mRNA requires only a single processing reaction: an endonucleolytic cleavage between a conserved stem-loop and a purine-rich downstream element to form the 3' end. The stem-loop binding protein (SLBP) is required for processing, and following processing, histone mRNA is transported to the cytoplasm, where SLBP participates in translation of the histone mRNA\|We used radiolabeled probes generated by PCR targeting the open reading frame (ORF) to detect histones H2A, H2B, H3, H4, and H1 and used 7SK snRNA as a loading control (Fig. 2A). The abundance of histone H2A, H2B, H3, and H4 mRNAs is reduced to 37% to 70% of control levels in the SLBP knockdown cells when compared to the C2 control.	SIGNOR-265393
Q8IYT8	P09467	1	phosphorylation	down-regulates activity	0.2	Here, we demonstrate that, during deprivation of amino acid and growth factors, ULK1/2 directly phosphorylate key glycolytic enzymes including hexokinase (HK), phosphofructokinase 1 (PFK1), enolase 1 (ENO1), and the gluconeogenic enzyme fructose-1,6-bisphosphatase (FBP1).Phosphorylation of these enzymes leads to enhanced HK activity to sustain glucose uptake but reduced activity of FBP1 to block the gluconeogenic route and reduced activity of PFK1 and ENO1 to moderate drop of glucose-6-phosphate and to repartition more carbon flux to pentose phosphate pathway (PPP), maintaining cellular energy and redox homeostasis at cellular and organismal levels.Similar results were also obtained using ULK2 as the kinase (data not shown).	SIGNOR-274039
P35367	P63092	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 ‚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-256778
Q16512	Q969V6	1	phosphorylation	down-regulates activity	0.2	Although RHOA mediated actin polymerization accelerated MRTFA induced gene transcription, PKN1 and PKN2 inhibited the interaction of MRTFA with G-actin by phosphorylating MRTFA, causing increased serum response factor (SRF)-mediated expression of cardiac hypertrophy- and fibrosis associated genes.\|Further, we identified MRTFA as a novel substrate of PKN1 and PKN2 and found that MRTFA phosphorylation by PKN was considerably more effective than that by ROCK in vitro .	SIGNOR-280067
P53041	Q16543	1	dephosphorylation	down-regulates activity	0.672	Activation of protein kinase clients by the Hsp90 system is mediated by the cochaperone protein Cdc37. Cdc37 requires phosphorylation at Ser13\|PP5/Ppt1 regulates phosphorylation of Ser13-Cdc37 in vivo, directly affecting activation of protein kinase clients by Hsp90-Cdc37.	SIGNOR-248539
Q15628	P19438	2	binding	up-regulates activity	0.805	We have identified a novel 34 kda protein, designated tradd, that specifically interacts with an intracellular domain of tnfr1 tradd interacts with the death domain of tnfrsf1a to initiate distinct signaling cascades for two of the most important biological activities of tnf, nf-kb activation and programmed cell death tradd, a novel protein that specifically interacts with the death domain of tnfr1 and activates signaling pathways for both of these activities when overexpressed.	SIGNOR-32739
Q9UNS1	Q16526	2	binding	up-regulates activity	0.674	We performed a detailed molecular characterization of TIM interactions with the core clock protein CRY1 and the DNA damage signal transducer CHK1, and found that the N-terminus of TIM is required for association with both proteins, as well as for homodimerization.	SIGNOR-268053
P06493	Q14106	1	phosphorylation	up-regulates activity	0.2	Taken together, these observations strongly support the notion that several different CDK-cyclin complexes are involved in the phosphorylation of Tob2 at S254.A more detailed regulatory context of Tob2 phosphorylation at S254 is provided by our findings from mass-spec and in vitro kinase analyses that suggest connections to PP2B and PP2C phosphatases and CDK-cyclin complexes, particularly CDK1, CDK2, and CDK4 (Table 1; Supplemental Table S2).One possibility is that the phosphorylation of S254 helps stabilize the interaction of Tob2 with the Ccr4–Not complex, which could contribute to Tob2's ability to recruit the entire Ccr4–Not complex and thus further enhances deadenylation.	SIGNOR-273591
P31751	Q92900	1	phosphorylation	up-regulates activity	0.2	AKT-Mediated UPF1 Phosphorylation at T151 Promotes UPF1 Helicase Activity	SIGNOR-277595
P28566	P08754	2	binding	up-regulates activity	0.448	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-256848
P36888	Q14469	0	transcriptional regulation	down-regulates quantity by repression	0.2	We then found that Hes1 directly bound to the promoter region of the FMS-like tyrosine kinase 3 (FLT3) gene and downregulated the promoter activity.	SIGNOR-261563
Q96NT3	P46934	0	polyubiquitination	down-regulates quantity by destabilization	0.419	The E3 ligase NEDD4 regulates GUCD1 degradation. many polyubiquitinylated species of GUCD1 appeared as high molecular weight forms, suggesting that GUCD1 is degraded by the proteasome, after polyubiquitin chain formation, in the presence of NEDD4-1.	SIGNOR-272846
P54132	P52701	2	binding	up-regulates	0.6	We show that the recombinant hmsh2/6 protein complex stimulated the ability of the bloom's syndrome gene product, blm, to process holliday junctions in vitro	SIGNOR-123705
P20962	Q15788	2	binding	up-regulates activity	0.2	Macromolecular translocation inhibitor II (MTI-II), which was first identified as an in vitro inhibitor of binding between the highly purified glucocorticoid receptor (GR) and isolated nuclei, is an 11.5-kDa Zn2+-binding protein that is also known as ZnBP or parathymosin. MTI-II Enhances GR-dependent Transcription through Its Acidic Domain. MTI-II Enhances GR-dependent Transcription in Cooperation with SRC-1 and p300 in Vivo. CBP and p300 Coprecipitate with MTI-II in a Glucocorticoid Hormone-dependent Manner. Immunoprecipitation analysis showed that in the presence of glucocorticoid hormone, p300 and CREB-binding protein are coprecipitated with MTI-II. Furthermore, the knockdown of endogenous MTI-II by RNAi reduces the transcriptional activity of GR in cells.	SIGNOR-268462
Q06187	Q00987	1	phosphorylation	down-regulates activity	0.278	Phosphorylation of MDM2 by BTK suppresses its ubiquitination activity.	SIGNOR-278330
Q12778	Q9HCE7	1	transcriptional regulation	up-regulates quantity	0.248	FoxO factors are required for the transcriptional regulation of the ubiquitin ligases atrogin-1, also called muscle atrophy F-box (MAFbx) and muscle ring finger 1 (MuRF1), leading to the ubiquitylation of myosin and other muscle proteins (see below), and their degradation via the proteasome	SIGNOR-256268
P18848	P23381	1	transcriptional regulation	up-regulates quantity by expression	0.2	QRICH1 promotes the expression of translation-related genes. our combined ChIP-seq and RNA-seq analyses identified that QRICH1 and ATF4 were enriched at the promoters of these specific tRNA synthetases, and that ER stress positively regulated their transcription (Fig. 4I). Together, these findings suggest that QRICH1 and ATF4 modulate tRNA metabolic processes to promote secreted protein synthesis during ER stress.	SIGNOR-269429
P49768	Q96BI3	2	binding	up-regulates	0.947	By using co-immunoprecipitation and nickel affinity pull-down approaches, we now show that mammalian aph-1 (maph-1), a conserved multipass membrane protein, physically associates with nicastrin and the heterodimers of the presenilin amino- and carboxyl-terminal fragments in human cell lines and in rat brain.	SIGNOR-93262
P38405	P32245	2	binding	up-regulates activity	0.27	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-256940
Q7Z3C6	O75385	0	phosphorylation	up-regulates activity	0.582	Src phosphorylates mATG9 at Tyr8 to maintain its endocytic and constitutive trafficking in unstressed conditions. In response to starvation, phosphorylation of mATG9 at Tyr8 by Src and at Ser14 by ULK1 functionally cooperate to promote interactions between mATG9 and the AP1/2 complex, leading to redistribution of mATG9 from the plasma membrane and juxta-nuclear region to the peripheral pool for autophagy initiation.	SIGNOR-266369
P36888	P35222	1	phosphorylation	up-regulates activity	0.409	Endogenous beta-catenin co-immunoprecipitated with endogenous activated FLT3, and recombinant activated FLT3 directly phosphorylated recombinant beta-catenin. Finally, FLT3 inhibitor decreased tyrosine phosphorylation of beta-catenin in leukemia cells obtained from FLT3-ITD-positive AML patients. These data demonstrate that FLT3 activation induces beta-catenin tyrosine phosphorylation and nuclear localization, and thus suggest a mechanism for the association of FLT3 activation and beta-catenin oncogeneic signaling in AML.	SIGNOR-260124
Q9ULW0	Q7Z460	2	binding	up-regulates activity	0.499	Phosphorylation of TPX2 regulated its interaction with CLASP1 but not Kif2a.\|This suggests that TPX2 phosphorylation positively regulates the function of CLASP1.\| This is in accord with a phosphoproteomics study that identified S121 and S125 as potential phosphorylation sites for Aurora A in mitotic HeLa cells	SIGNOR-265090
P20827	P54764	2	binding	up-regulates	0.823	Receptors of the epha group preferentially interact with glycosylphosphatidylinositol (gpi)-linked ligands (of the ephrin-a subclass, which comprises five ligands), while receptors of the ephb group preferentially interact with transmembrane ligands (of the ephrin-b subclass, which comprises three ligands) (table 1). In either case, binding of a ligand results in eph receptor autophosphorylation on tyrosine residues and activation of the kinase activity of the eph receptor	SIGNOR-52087
O60291	P51668	2	binding	up-regulates activity	0.496	Our in vivo and in vitro ubiquitylation studies demonstrate that the binding of TSG101 to Mahogunin targets the substrate TSG101 for ubiquitylation by Mahogunin E3 ligase in cooperation with its cognate E2 enzyme Ubc5a	SIGNOR-271637
O75177	Q92793	1	relocalization	up-regulates	0.397	The calcium-responsive transactivator recruits creb binding protein to nuclear bodies.	SIGNOR-129926
P62140	Q13422	1	dephosphorylation	up-regulates	0.265	Ikarosis dephosphorylated by protein phosphatase 1 (pp1) via interaction at a consensus pp1-binding motif/ hyperphosphorylation of ikaros promotes its degradation by the ubiquitin/proteasome pathway	SIGNOR-174862
Q9Y222	P18146	1	transcriptional regulation	up-regulates quantity by expression	0.2	Notably, amphiregulin (Areg), thrombospondin-1 (Tsp-1), JunB, Egr1, adrenomedullin (Adm), Bcl-3 and methyl-CpG binding domain protein 1 (Mbd1) were downregulated in the lungs from Dmp1-null mice while Gas1 and Ect2 genes were upregulated.	SIGNOR-261584
P41134	P15923	2	binding	down-regulates activity	0.634	All three Ids bound with high affinity to E proteins .Each Id was able to disrupt the ability of E protein-MyoD complexes to transactivate from a muscle creatine kinase reporter construct in vivo.	SIGNOR-241107
P45983	Q96KB5	0	phosphorylation	up-regulates activity	0.303	Taken together, these findings showed that TOPK positively modulated UVB-induced JNK1 activity and played a pivotal role in JNK1-mediated cell transformation induced by H-Ras.\|We showed that TOPK associated with and phosphorylated JNK1 following UVB irradiation in vitro or in vivo.	SIGNOR-280061
P35222	Q9HCK8	2	binding	down-regulates	0.644	Duplin (axis duplication inhibitor) interacts with beta-catenin and prevents its binding to tcf, thereby inhibiting downstream wnt signaling	SIGNOR-128976
P59594	P35354	1	transcriptional regulation	up-regulates activity	0.2	Spike protein of SARS‐CoV activated COX‐2 expression in a protein concentration‐dependent manner	SIGNOR-262315
P12931	Q14847	1	phosphorylation	up-regulates activity	0.253	Integrin-dependent translocation of LASP-1 to the cytoskeleton of activated platelets correlates with LASP-1 phosphorylation at tyrosine 171 by Src-kinase	SIGNOR-271706
P31751	Q6ZVD8	0	dephosphorylation	down-regulates activity	0.604	The Abl kinase inhibitors and depletion of Bcr-Abl induced the expression of PHLPP1 and PHLPP2, which dephosphorylated Ser-473 on Akt1, -2, and -3, resulting in inhibited proliferation of CML cells.\|Thus, Bcr-Abl represses the expression of PHLPP1 and PHLPP2 and continuously activates Akt1, -2, and -3 via phosphorylation on Ser-473, resulting in the proliferation of CML cells.	SIGNOR-248729
Q15596	P19793	2	binding	up-regulates	0.798	Here, it is demonstrated that mutation of the h11 phenylalanine residues diminishes the ability of rxr to associate with the p160 coactivators tif2 and p/cip, but has little effect on ligand-dependent interactions of the receptor with the unrelated coactivator tif1.	SIGNOR-114847
Q9H3Y6	P45985	1	phosphorylation	down-regulates activity	0.2	SRMS directly phosphorylates MKK4 and inhibits MKK4-JNK-c-Jun activation upon platinum treatment. Platinum treatment-induced ROS activates SRMS, which inhibits MKK4 kinase activity by directly phosphorylating MKK4 at Y269 and Y307, and consequently attenuates MKK4-JNK activation.	SIGNOR-277902
P31751	P49815	1	phosphorylation	down-regulates	0.729	We demonstrate here that tuberin is phosphorylated on s939 and t1462 in response to pi3k activation. Our results are consistent with akt being the pi3k-depen-dent tuberin kinase. The pi3k-akt-mediated phosphorylation of tuberin would inhibit the function of the tuberin-hamartin complex.	SIGNOR-91041
O15525	P27361	0	phosphorylation	up-regulates quantity	0.368	By contrast, MAFG-S124A was not phosphorylated, indicating that ERK1 phosphorylates MAFG at S124.\|Notably, cotransfection of ERK1 increased total levels of wild-type MAFG and MAFG-T3A but not MAFG-S124A, indicating that phosphorylation increased MAFG stability.	SIGNOR-280027
P24941	P15172	1	phosphorylation	down-regulates	0.522	Cyclin e/cdk2 can phosphorylate myod at serine 200, which causes ubiquitination and degradation of this transcription factor during g1, preventing its accumulation and a commitment to differentiation.	SIGNOR-176509
P04637	Q96EB6	0	deacetylation	down-regulates	0.803	Sirt1 has been shown to regulate cell fate in part by deacetylating the p53 protein at lysine 382 and inhibiting p53-mediated transcriptional activation and apoptosis.	SIGNOR-182515
Q6ZN44	Q9HB63	2	binding	up-regulates	0.61	The unc5hs are axon guidance receptors that mediate netrin-1-dependent chemorepulsion, and dependence receptors that mediate netrin-1-independent apoptosis.	SIGNOR-98483
P12830	Q5T0T0	0	ubiquitination	down-regulates quantity by destabilization	0.2	Inhibiting proteasome activity with MG132 prevented CDH1 and beta2M degradation, indicating that MARCH8 might be targeting CDH1 and beta2M for proteasomal degradation.\|We demonstrated that MARCH8 interacts with and ubiquitinates CDH1 and beta2M.	SIGNOR-278820
P17612	Q8N5S9	1	phosphorylation	down-regulates activity	0.2	In vitro, CaMKK is phosphorylated by PKA and this is associated with inhibition of enzyme activity. The major site of phosphorylation is threonine 108, although additional sites are phosphorylated with lower efficiency.	SIGNOR-256115
Q00535	O60229	1	phosphorylation	up-regulates activity	0.4	We then demonstrated that Cdk5 phosphorylates Kalirin 7 on Thr 1590 , increasing its GEF activity slightly and changing its solubility properties.	SIGNOR-279603
P01106	P61244	2	binding	up-regulates	0.743	In vivo transactivation assays suggest that myc-max and mad-max complexes have opposing functions in transcription and that max plays a central role in this network of transcription factors	SIGNOR-39137
P42772	Q8IXJ9	0	transcriptional regulation	up-regulates quantity by expression	0.276	Tumor suppressor ASXL1 is essential for the activation of INK4B expression in response to oncogene activity and anti-proliferative signals	SIGNOR-241759
Q9UIJ5	P78352	1	palmitoylation	up-regulates activity	0.379	Plasma membrane targeting of DHHC2 palmitoyltransferase rapidly recruited PSD-95 to the plasma membrane and proved essential for postsynaptic nanodomain formation.	SIGNOR-261290
Q00610	Q676U5	2	binding	up-regulates	0.46	Clathrin heavy-chain interacts with atg16l1, and is involved in the formation of atg16l1-positive early autophagosome precursors.	SIGNOR-166702
P20701	Q99996	2	binding	up-regulates activity	0.2	However, association of CG-NAP/AKAP450 was signifi-cantly enhanced at 37°C in LFA-1-activated cells triggered toundergo motility. Taken together, our findings provide the first definitiveevidence that the protein CG-NAP/AKAP450 is a key scaffoldingcomponent of the multimolecular complex assembled in T cellsupon LFA cross-linking and is functionally indispensable for cellpolarity and migration induced by this integrin.	SIGNOR-260304
P52797	P29317	2	binding	up-regulates	0.814	The eph family of receptors.	SIGNOR-52309
Q9ULJ6	P01106	1	transcriptional regulation	up-regulates quantity by expression	0.362	The N-terminal domain (NTD) of Zmiz1 is important for driving Myc transcription and proliferation […] Zmiz1 directly interacted with Notch1 via a tetratricopeptide repeat domain at a special class of Notch-regulatory sites.	SIGNOR-263939
P08151	Q9UMX1	2	binding	down-regulates activity	0.949	Here we characterize structural and functional determinants of Su(fu) required for Gli regulation and show that Su(fu) contains at least two distinct domains: a highly conserved carboxy-terminal region required for binding to the amino-terminal ends of the Gli proteins and a unique amino-terminal domain that binds the carboxy-terminal tail of Gli1. While each domain is capable of binding to different Gli1 regions independently, interactions between Su(fu) and Gli1 at both sites are required for cytoplasmic tethering and repression of Gli1	SIGNOR-249591
O14686	P23759	2	binding	up-regulates	0.304	Carm1 specifically methylates multiple arginines in the n-terminus of pax7. Methylated pax7 directly binds the c-terminal cleavage forms of the trithorax proteins mll1/2 resulting in the recruitment of the ash2l:mll1/2:wdr5:rbbp5 histone h3k4 methyltransferase complex to regulatory enhancers and the proximal promoter of myf5.	SIGNOR-198629
Q9Y490	Q05397	2	binding	up-regulates activity	0.688	Focal adhesion kinase (FAK) is activated by growth factors and integrins during migration, and functions as a receptor-proximal regulator of cell motility. At contacts between cells and the extracellular matrix, FAK functions as an adaptor protein to recruit other focal contact proteins or their regulators, which affects the assembly or disassembly of focal contacts. Whereas it was first hypothesized that FAK might bind directly to the cytoplasmic tails of integrins, accumulated evidence supports an indirect association of FAK with integrins through binding to integrin-associated proteins such as paxillin and talin.	SIGNOR-257731
Q9BUF5	Q14980	2	binding	up-regulates	0.2	Direct binding of numa to tubulin is mediated by a novel sequence motif in the tail domain that bundles and stabilizes microtubules.	SIGNOR-117109
P49841	Q9Y4K4	0	phosphorylation	down-regulates	0.2	Gckr can phosphorylate an n-terminal recombinant fusion protein of gsk3_ and enhance the in vivo phosphorylation of gsk3_ on serine 9reduction of gckr expression inhibits wnt3a-induced phosphorylation of gsk3_ at serine 9 and decreases the accumulation of cytosolic _-catenin.	SIGNOR-148908
Q13131	P35638	1	phosphorylation	down-regulates activity	0.265	Here, we report that phosphorylation of CHOP at Ser30 by AMPKα1 triggers CHOP degradation resulting in reduced macrophage apoptosis and subsequent ameliorated plaque vulnerability in vivo.	SIGNOR-259864
P42224	Q02763	0	phosphorylation	up-regulates activity	0.301	Tie2-R849W induced STAT1 phosphorylation at Y701 independent of ligand stimulation.\|Together, Tie2-R849W induced functional activation of STAT1, leading to increased expression of STAT1-responsive gene like IRF1.	SIGNOR-279131
P42224	P52630	2	binding	up-regulates activity	0.555	We then examined STAT2 acetylation within the b-barrel DBD. A direct interaction between the STAT2-DBD (315485) and STAT1 was detected (Figure 6E) (Li et al., 1997).	SIGNOR-217957
P17542	Q02750	0	phosphorylation	down-regulates	0.2	We found that hypoxia greatly accelerated tal1 turnover in these cells through mitogen-activated protein kinase (mapk)2-mediated phosphorylation, ubiquitination, and proteasomal degradation.	SIGNOR-116149
P10415	P28482	0	phosphorylation	up-regulates quantity by stabilization	0.552	Phosphorylation of the map kinase sites in bcl-2, thr56, thr74, and ser87, is sufficient to inhibit tnf--induced degradation.	SIGNOR-74931
P21918	P19086	2	binding	up-regulates activity	0.404	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-257311
P10636	P48730	0	phosphorylation	down-regulates	0.374	Casein kinase 1 delta phosphorylates tau and disrupts its binding to microtubules.Here we characterized the contribution of one ck1 isoform, ckidelta, to the phosphorylation of tau at residues ser202/thr205 and ser396/ser404 in human embryonic kidney 293 cells.	SIGNOR-121717
Q04725	Q9UJU2	2	binding	down-regulates	0.638	Mapping studies reveal that groucho/tle binds two regions in lef-1.	SIGNOR-185736
P17252	P13498	1	phosphorylation	up-regulates	0.2	Phosphorylation of p22phox on threonine 147 enhances NADPH oxidase activity by promoting p47phox binding. \| Threonine 147 of p22phox Is Phosphorylated by PKC-α and PKC-δ in Vitro	SIGNOR-260891
Q14653	Q7Z434	2	binding	up-regulates activity	0.8	Phosphorylated MAVS and STING then bind to a positively charged surface of interferon regulatory factor 3 (IRF3) and thereby recruit IRF3 for its phosphorylation and activation by TBK1.	SIGNOR-260143
Q96T68	P84243	1	methylation	up-regulates activity	0.2	Here, we have characterized a previously undescribed member of the histone H3K9 methyltransferase family named CLLD8 (or SETDB2 or KMT1F). This protein contributes to the trimethylation of both interspersed repetitive elements and centromere-associated repeats and participates in the recruitment of heterochromatin protein 1 to centromeres. Methylation of histone H3 at lysine 9 (H3K9) has emerged as an important player in the formation of heterochromatin, chromatin condensation, and transcriptional repression.	SIGNOR-263894
P18509	P41586	2	binding	up-regulates	0.877	Type i pacap receptors bind pacap-27 and -38. the potencies of the two forms of pacap are similar for adenylate cyclase stimulation, whereas pacap-38 is more potent than pacap-27 in phospholipase c activation.	SIGNOR-43225
P00519	Q14498	1	phosphorylation	up-regulates activity	0.322	In this paper, we report that RBM39 interacts with the nonreceptor tyrosine kinase c-Abl. Both the Src homology (SH) 2 and SH3 domains of c-Abl interact with RBM39. The major tyrosine phosphorylation sites on RBM39 that are phosphorylated by c-Abl are Y95 and Y99, as demonstrated by liquid chromatography coupled with tandem mass spectrometry (LC/MS/MS) and mutational analysis. c-Abl was shown boost the transcriptional coactivation activity of RBM39 for ERα and PRβ in a tyrosine kinase-dependent manner.	SIGNOR-262609
P23588	P60842	2	binding	up-regulates activity	0.867	Either eIF4B or eIF4H stimulated the initial rate and amplitude of eIF4A-dependent duplex unwinding, and the magnitude of stimulation is dependent on duplex stability	SIGNOR-261293
Q13526	Q15468	2	binding	up-regulates	0.361	Cell cycle-dependent phosphorylation of sil is required for its interaction with pin1, a regulator of mitosis. Point mutation of the seven (s/t)p sites between amino acids 567 and 760 reduces mitotic phosphorylation of sil, pin1 binding, and spindle checkpoint duration.	SIGNOR-138677
Q53ET0	P04150	2	binding	up-regulates activity	0.294	We show here that CRTC2 also functions as a coactivator for the glucocorticoid receptor (GR).	SIGNOR-256101
P17987	P36508	0	transcriptional regulation	up-regulates quantity by expression	0.347	The transcription from the minimalCcta promoter was up-regulated 3-fold by ZNF143 and 6-fold by ZNF76 when full-length proteins were co-expressed, indicating that both ZNF143 and ZNF76 can enhance Ccta transcription.	SIGNOR-266221
O15516	Q7Z5J4	0	transcriptional regulation	up-regulates quantity by expression	0.479	RAI1 Transcriptionally Activates CLOCK via an Intron 1 Enhancer Element. data suggest that RAI1 binds, directly or in a complex, to the first intron of CLOCK and enhances its transcriptional activity in vitro, supporting RAI1 as a positive regulator of CLOCK and an important part of the circadian loop of transcription. Data further show that haploinsufficiency of RAI1 and Rai1 in SMS fibroblasts and the mouse hypothalamus, respectively, results in the transcriptional dysregulation of the circadian clock and causes altered expression and regulation of multiple circadian genes, including PER2, PER3, CRY1, BMAL1, and others.	SIGNOR-266839
P49761	P01106	0	transcriptional regulation	up-regulates quantity by expression	0.2	C-Myc enhances transcriptional activation of CLK3 promoter in CCA cells.	SIGNOR-274123
Q96CN5	Q68D86	2	binding	up-regulates activity	0.2	CCDC102B is recruited to the centrosome by C-Nap1 (also known as CEP250) and interacts with the centrosome linker components rootletin and LRRC45. CCDC102B decorates and facilitates the formation of rootletin filaments. Furthermore, CCDC102B is phosphorylated by Nek2A (an isoform encoded by NEK2) and is disassociated from the centrosome at the onset of mitosis.	SIGNOR-275627
Q6JBY9	P53778	0	phosphorylation	down-regulates activity	0.504	Peptide T2 was sequenced and shown to comprise residues 79–112 of CapZIP, phosphorylated at Ser-108 (Figure 2B). The identity of peptide T1 is unknown. These experiments established that the SAPK3/p38γ substrate was CapZIP. Using this antibody, we showed by immunoblotting that bacterially expressed CapZIP was phosphorylated at Ser-108 by SAPK4/p38δ, JNK1α1 and ERK2 in vitro, as well as by SAPK3/p38γ (results not shown). An important clue to the function of CapZIP and its phosphorylation came from the finding that it binds to the actin-capping protein CapZ (Figure 7A), and that cellular stresses trigger the dissociation of these two proteins (Figure 7B).Such an effect is presumably lost when CapZIP is phosphorylated and dissociates from CapZ.	SIGNOR-263083
P19484	P11802	0	phosphorylation	up-regulates activity	0.2	CDK4 and CDK6 phosphorylate TFEB and TFE3.	SIGNOR-279450
Q12913	P28482	1	dephosphorylation	down-regulates	0.406	In this study we show that one of these potential targets, the erk1/2, is indeed a direct dep-1 substrate in vivo.	SIGNOR-161536
P04637	Q00653	2	binding	up-regulates	0.425	P52 cooperates with p53 to regulate other known p53 target genes.	SIGNOR-149811
P63092	P08588	2	binding	up-regulates activity	0.527	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-256758
A1L390	P60953	1	guanine nucleotide exchange factor	up-regulates activity	0.354	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-260585
Q03113	P28335	2	binding	up-regulates activity	0.277	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-257405
P17612	P17752	1	phosphorylation	up-regulates activity	0.35	The activation of tryptophan hydroxylase by protein kinase A is mediated by the phosphorylation of serine-58 within the regulatory domain of the enzyme.	SIGNOR-250062
P38398	Q00341	2	binding	up-regulates activity	0.2	We show that vigilin interacts with the DNA damage response (DDR) proteins RAD51 and BRCA1, and vigilin depletion impairs their recruitment to DSB sites.	SIGNOR-266698
Q13351	P68400	0	phosphorylation	up-regulates activity	0.344	Regulation of erythroid Krppel-like factor (EKLF) transcriptional activity by phosphorylation of a protein kinase casein kinase II site within its interaction domain. the transactivation capability of EKLF is augmented by co-transfection of CKIIalpha. in vitro assays demonstrate that CKIIalpha interacts with EKLF, and that the EKLF interaction domain is phosphorylated by CKII only at Thr-41	SIGNOR-241361
O76064	Q969R5	1	ubiquitination	up-regulates activity	0.242	L3MBTL2 links RNF8 and RNF168 in the DNA double strand break response. The protein kinase ATM phosphorylates L3MBTL2, which recruits it to the DNA lesion by promoting the interaction between MDC1 and L3MBTL2. L3MBTL2 is subsequently ubiquitinated by RNF8, which acts as a docking site for RNF168, thereby recruiting the ubiquitin ligase to the damage site. RNF168, in turn, ubiquitinates H2A-type histones to amplify the DNA damage response and recruit downstream DNA repair proteins for proper DSB signaling.	SIGNOR-266787
P27361	Q9UIG0	1	phosphorylation	up-regulates	0.2	Wstf, a specific component of two chromatin remodeling complexes (swi/snf-type winac and iswi-type wich), was phosphorylated by the stimulation of mapk cascades in vitro and in vivo. Ser-158 residue in the wac (wstf/acf1/cbpq46) domain, located close to the n terminus of wstf, was identified as a major phosphorylation target	SIGNOR-188164

P19086

Q99500

2

binding

up-regulates activity

0.385

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-257330

P17612

Q07343

1

phosphorylation

up-regulates activity

0.605

PKA-mediated phosphorylation of Ser-56 in UCR1 of PDE4B4 leads to activation of this long isoform

SIGNOR-250024

Q14896

Q05655

0

phosphorylation

up-regulates

0.2

The triple aspartic acid mutation shows greater distance between the two thick myosin filaments (affects the steric arrangement of the filament distances) in heart tissue. Mutation is cardioprotective during stress (ischemia-reprofusion injury) against apoptosis similar to isoproterenol treatment.

SIGNOR-150355

P43694

P11802

0

phosphorylation

up-regulates activity

0.356

In addition, we have shown that CDK4 can enhance cardiogenic activity of GATA4 (XREF_FIG).|The physical and functional interactions between GATA4 and Cyclin D2 depend on phosphorylation of Ser 160 of GATA4, which can be mediated in vitro by CDK4.

SIGNOR-279148

Q99683

P46734

1

phosphorylation

up-regulates activity

0.599

Ask1 is a member of a mapkkk family and functions as an upstream kinase engaged in c-jun nh2-terminal kinase (jnk)/p38 signaling via the phosphorylation and activation of mapkks, such as mkk3, -4, -6, and -7

SIGNOR-161763

P12931

P24666

0

dephosphorylation

up-regulates activity

0.438

LMWPTP dephosphorylated pY(527)-Src and pY(416)-Src in vitro, with greater specificity for pY(527)Src. Activation of LMWPTP produced strong activation of Src mediated by fast dephosphorylation of pY(527)-Src, followed by slower deactivation of this kinase via dephosphorylation of pY(416)Src.

SIGNOR-248454

P50750

Q15596

1

phosphorylation

up-regulates activity

0.246

Interestingly, GRIP1 is phosphorylated at an N-terminal serine cluster by cyclin-dependent kinase-9 (CDK9), which is recruited into GC-induced GR:GRIP1:CDK9 hetero-complexes, producing distinct GRE-specific GRIP1 phospho-isoforms. Phosphorylation potentiates GRIP1 coactivator but, remarkably, not its corepressor properties.

SIGNOR-256098

O95837

P30559

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-257332

Q14643

Q9BS26

2

binding

down-regulates activity

0.58

In this study, we found that ERp44, an ER lumenal protein of the thioredoxin family, directly interacts with the third lumenal loop of IP(3)R type 1 (IP(3)R1) and that the interaction is dependent on pH, Ca(2+) concentration, and redox state. In this study we demonstrated that ERp44 directly interacts with the L3V domain of IP3R1, thereby inhibiting its channel activity.

SIGNOR-261046

Q14164

P35813

0

dephosphorylation

down-regulates activity

0.279

PPM1A directly dephosphorylates both MAVS and TBK1 and IKKepsilon.|In a similar in vitro phosphatase assay, incubation of PPM1A also eliminated TBK1 and IKKepsilon phosphorylation at Ser 172 residue, evidenced by phospho-S172 immunoblotting (XREF_FIG, F and G).|These observations suggest that PPM1A may block kinase activities of TBK1 and IKKepsilon.

SIGNOR-277072

Q9BTC0

P08648

1

transcriptional regulation

up-regulates quantity by expression

0.2

Dido1 upregulates the expression of Integrin αV, thereby influencing the attachment, apoptosis and migration of melanoma cells.

SIGNOR-261580

P36873

P51955

0

phosphorylation

down-regulates

0.488

Pp1 is a substrate for nek2 and phosphorylation of pp1gamma(1) on two c-terminal sites reduces its phosphatase activity.

SIGNOR-78603

Q9BZR9

O43318

1

polyubiquitination

up-regulates activity

0.343

These results suggest that TRIM8 could mediate K63-linked polyubiquitination of TAK1 at residue K158.These results suggest that TRIM8 is involved in TNFα- and IL-1β–induced NF-κB activation by mediating K63-linked TAK1 polyubiquitination and subsequent activation.

SIGNOR-271890

Q14493

Q96A08

1

translation regulation

up-regulates quantity by expression

0.2

Synthesis of mature histone mRNA requires only a single processing reaction: an endonucleolytic cleavage between a conserved stem-loop and a purine-rich downstream element to form the 3' end. The stem-loop binding protein (SLBP) is required for processing, and following processing, histone mRNA is transported to the cytoplasm, where SLBP participates in translation of the histone mRNA|We used radiolabeled probes generated by PCR targeting the open reading frame (ORF) to detect histones H2A, H2B, H3, H4, and H1 and used 7SK snRNA as a loading control (Fig. 2A). The abundance of histone H2A, H2B, H3, and H4 mRNAs is reduced to 37% to 70% of control levels in the SLBP knockdown cells when compared to the C2 control.

SIGNOR-265393

Q8IYT8

P09467

1

phosphorylation

down-regulates activity

0.2

Here, we demonstrate that, during deprivation of amino acid and growth factors, ULK1/2 directly phosphorylate key glycolytic enzymes including hexokinase (HK), phosphofructokinase 1 (PFK1), enolase 1 (ENO1), and the gluconeogenic enzyme fructose-1,6-bisphosphatase (FBP1).Phosphorylation of these enzymes leads to enhanced HK activity to sustain glucose uptake but reduced activity of FBP1 to block the gluconeogenic route and reduced activity of PFK1 and ENO1 to moderate drop of glucose-6-phosphate and to repartition more carbon flux to pentose phosphate pathway (PPP), maintaining cellular energy and redox homeostasis at cellular and organismal levels.Similar results were also obtained using ULK2 as the kinase (data not shown).

SIGNOR-274039

P35367

P63092

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 ‚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-256778

Q16512

Q969V6

1

phosphorylation

down-regulates activity

0.2

Although RHOA mediated actin polymerization accelerated MRTFA induced gene transcription, PKN1 and PKN2 inhibited the interaction of MRTFA with G-actin by phosphorylating MRTFA, causing increased serum response factor (SRF)-mediated expression of cardiac hypertrophy- and fibrosis associated genes.|Further, we identified MRTFA as a novel substrate of PKN1 and PKN2 and found that MRTFA phosphorylation by PKN was considerably more effective than that by ROCK in vitro .

SIGNOR-280067

P53041

Q16543

1

dephosphorylation

down-regulates activity

0.672

Activation of protein kinase clients by the Hsp90 system is mediated by the cochaperone protein Cdc37. Cdc37 requires phosphorylation at Ser13|PP5/Ppt1 regulates phosphorylation of Ser13-Cdc37 in vivo, directly affecting activation of protein kinase clients by Hsp90-Cdc37.

SIGNOR-248539

Q15628

P19438

2

binding

up-regulates activity

0.805

We have identified a novel 34 kda protein, designated tradd, that specifically interacts with an intracellular domain of tnfr1 tradd interacts with the death domain of tnfrsf1a to initiate distinct signaling cascades for two of the most important biological activities of tnf, nf-kb activation and programmed cell death tradd, a novel protein that specifically interacts with the death domain of tnfr1 and activates signaling pathways for both of these activities when overexpressed.

SIGNOR-32739

Q9UNS1

Q16526

2

binding

up-regulates activity

0.674

We performed a detailed molecular characterization of TIM interactions with the core clock protein CRY1 and the DNA damage signal transducer CHK1, and found that the N-terminus of TIM is required for association with both proteins, as well as for homodimerization.

SIGNOR-268053

P06493

Q14106

1

phosphorylation

up-regulates activity

0.2

Taken together, these observations strongly support the notion that several different CDK-cyclin complexes are involved in the phosphorylation of Tob2 at S254.A more detailed regulatory context of Tob2 phosphorylation at S254 is provided by our findings from mass-spec and in vitro kinase analyses that suggest connections to PP2B and PP2C phosphatases and CDK-cyclin complexes, particularly CDK1, CDK2, and CDK4 (Table 1; Supplemental Table S2).One possibility is that the phosphorylation of S254 helps stabilize the interaction of Tob2 with the Ccr4–Not complex, which could contribute to Tob2's ability to recruit the entire Ccr4–Not complex and thus further enhances deadenylation.

SIGNOR-273591

P31751

Q92900

1

phosphorylation

up-regulates activity

0.2

AKT-Mediated UPF1 Phosphorylation at T151 Promotes UPF1 Helicase Activity

SIGNOR-277595

P28566

P08754

2

binding

up-regulates activity

0.448

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-256848

P36888

Q14469

0

transcriptional regulation

down-regulates quantity by repression

0.2

We then found that Hes1 directly bound to the promoter region of the FMS-like tyrosine kinase 3 (FLT3) gene and downregulated the promoter activity.

SIGNOR-261563

Q96NT3

P46934

0

polyubiquitination

down-regulates quantity by destabilization

0.419

The E3 ligase NEDD4 regulates GUCD1 degradation. many polyubiquitinylated species of GUCD1 appeared as high molecular weight forms, suggesting that GUCD1 is degraded by the proteasome, after polyubiquitin chain formation, in the presence of NEDD4-1.

SIGNOR-272846

P54132

P52701

2

binding

up-regulates

0.6

We show that the recombinant hmsh2/6 protein complex stimulated the ability of the bloom's syndrome gene product, blm, to process holliday junctions in vitro

SIGNOR-123705

P20962

Q15788

2

binding

up-regulates activity

0.2

Macromolecular translocation inhibitor II (MTI-II), which was first identified as an in vitro inhibitor of binding between the highly purified glucocorticoid receptor (GR) and isolated nuclei, is an 11.5-kDa Zn2+-binding protein that is also known as ZnBP or parathymosin. MTI-II Enhances GR-dependent Transcription through Its Acidic Domain. MTI-II Enhances GR-dependent Transcription in Cooperation with SRC-1 and p300 in Vivo. CBP and p300 Coprecipitate with MTI-II in a Glucocorticoid Hormone-dependent Manner. Immunoprecipitation analysis showed that in the presence of glucocorticoid hormone, p300 and CREB-binding protein are coprecipitated with MTI-II. Furthermore, the knockdown of endogenous MTI-II by RNAi reduces the transcriptional activity of GR in cells.

SIGNOR-268462

Q06187

Q00987

1

phosphorylation

down-regulates activity

0.278

Phosphorylation of MDM2 by BTK suppresses its ubiquitination activity.

SIGNOR-278330

Q12778

Q9HCE7

1

transcriptional regulation

up-regulates quantity

0.248

FoxO factors are required for the transcriptional regulation of the ubiquitin ligases atrogin-1, also called muscle atrophy F-box (MAFbx) and muscle ring finger 1 (MuRF1), leading to the ubiquitylation of myosin and other muscle proteins (see below), and their degradation via the proteasome

SIGNOR-256268

P18848

P23381

1

transcriptional regulation

up-regulates quantity by expression

0.2

QRICH1 promotes the expression of translation-related genes. our combined ChIP-seq and RNA-seq analyses identified that QRICH1 and ATF4 were enriched at the promoters of these specific tRNA synthetases, and that ER stress positively regulated their transcription (Fig. 4I). Together, these findings suggest that QRICH1 and ATF4 modulate tRNA metabolic processes to promote secreted protein synthesis during ER stress.

SIGNOR-269429

P49768

Q96BI3

2

binding

up-regulates

0.947

By using co-immunoprecipitation and nickel affinity pull-down approaches, we now show that mammalian aph-1 (maph-1), a conserved multipass membrane protein, physically associates with nicastrin and the heterodimers of the presenilin amino- and carboxyl-terminal fragments in human cell lines and in rat brain.

SIGNOR-93262

P38405

P32245

2

binding

up-regulates activity

0.27

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-256940

Q7Z3C6

O75385

0

phosphorylation

up-regulates activity

0.582

Src phosphorylates mATG9 at Tyr8 to maintain its endocytic and constitutive trafficking in unstressed conditions. In response to starvation, phosphorylation of mATG9 at Tyr8 by Src and at Ser14 by ULK1 functionally cooperate to promote interactions between mATG9 and the AP1/2 complex, leading to redistribution of mATG9 from the plasma membrane and juxta-nuclear region to the peripheral pool for autophagy initiation.

SIGNOR-266369

P36888

P35222

1

phosphorylation

up-regulates activity

0.409

Endogenous beta-catenin co-immunoprecipitated with endogenous activated FLT3, and recombinant activated FLT3 directly phosphorylated recombinant beta-catenin. Finally, FLT3 inhibitor decreased tyrosine phosphorylation of beta-catenin in leukemia cells obtained from FLT3-ITD-positive AML patients. These data demonstrate that FLT3 activation induces beta-catenin tyrosine phosphorylation and nuclear localization, and thus suggest a mechanism for the association of FLT3 activation and beta-catenin oncogeneic signaling in AML.

SIGNOR-260124

Q9ULW0

Q7Z460

2

binding

up-regulates activity

0.499

Phosphorylation of TPX2 regulated its interaction with CLASP1 but not Kif2a.|This suggests that TPX2 phosphorylation positively regulates the function of CLASP1.| This is in accord with a phosphoproteomics study that identified S121 and S125 as potential phosphorylation sites for Aurora A in mitotic HeLa cells

SIGNOR-265090

P20827

P54764

2

binding

up-regulates

0.823

Receptors of the epha group preferentially interact with glycosylphosphatidylinositol (gpi)-linked ligands (of the ephrin-a subclass, which comprises five ligands), while receptors of the ephb group preferentially interact with transmembrane ligands (of the ephrin-b subclass, which comprises three ligands) (table 1). In either case, binding of a ligand results in eph receptor autophosphorylation on tyrosine residues and activation of the kinase activity of the eph receptor

SIGNOR-52087

O60291

P51668

2

binding

up-regulates activity

0.496

Our in vivo and in vitro ubiquitylation studies demonstrate that the binding of TSG101 to Mahogunin targets the substrate TSG101 for ubiquitylation by Mahogunin E3 ligase in cooperation with its cognate E2 enzyme Ubc5a

SIGNOR-271637

O75177

Q92793

1

relocalization

up-regulates

0.397

The calcium-responsive transactivator recruits creb binding protein to nuclear bodies.

SIGNOR-129926

P62140

Q13422

1

dephosphorylation

up-regulates

0.265

Ikarosis dephosphorylated by protein phosphatase 1 (pp1) via interaction at a consensus pp1-binding motif/ hyperphosphorylation of ikaros promotes its degradation by the ubiquitin/proteasome pathway

SIGNOR-174862

Q9Y222

P18146

1

transcriptional regulation

up-regulates quantity by expression

0.2

Notably, amphiregulin (Areg), thrombospondin-1 (Tsp-1), JunB, Egr1, adrenomedullin (Adm), Bcl-3 and methyl-CpG binding domain protein 1 (Mbd1) were downregulated in the lungs from Dmp1-null mice while Gas1 and Ect2 genes were upregulated.

SIGNOR-261584

P41134

P15923

2

binding

down-regulates activity

0.634

All three Ids bound with high affinity to E proteins .Each Id was able to disrupt the ability of E protein-MyoD complexes to transactivate from a muscle creatine kinase reporter construct in vivo.

SIGNOR-241107

P45983

Q96KB5

0

phosphorylation

up-regulates activity

0.303

Taken together, these findings showed that TOPK positively modulated UVB-induced JNK1 activity and played a pivotal role in JNK1-mediated cell transformation induced by H-Ras.|We showed that TOPK associated with and phosphorylated JNK1 following UVB irradiation in vitro or in vivo.

SIGNOR-280061

P35222

Q9HCK8

2

binding

down-regulates

0.644

Duplin (axis duplication inhibitor) interacts with beta-catenin and prevents its binding to tcf, thereby inhibiting downstream wnt signaling

SIGNOR-128976

P59594

P35354

1

transcriptional regulation

up-regulates activity

0.2

Spike protein of SARS‐CoV activated COX‐2 expression in a protein concentration‐dependent manner

SIGNOR-262315

P12931

Q14847

1

phosphorylation

up-regulates activity

0.253

Integrin-dependent translocation of LASP-1 to the cytoskeleton of activated platelets correlates with LASP-1 phosphorylation at tyrosine 171 by Src-kinase

SIGNOR-271706

P31751

Q6ZVD8

0

dephosphorylation

down-regulates activity

0.604

The Abl kinase inhibitors and depletion of Bcr-Abl induced the expression of PHLPP1 and PHLPP2, which dephosphorylated Ser-473 on Akt1, -2, and -3, resulting in inhibited proliferation of CML cells.|Thus, Bcr-Abl represses the expression of PHLPP1 and PHLPP2 and continuously activates Akt1, -2, and -3 via phosphorylation on Ser-473, resulting in the proliferation of CML cells.

SIGNOR-248729

Q15596

P19793

2

binding

up-regulates

0.798

Here, it is demonstrated that mutation of the h11 phenylalanine residues diminishes the ability of rxr to associate with the p160 coactivators tif2 and p/cip, but has little effect on ligand-dependent interactions of the receptor with the unrelated coactivator tif1.

SIGNOR-114847

Q9H3Y6

P45985

1

phosphorylation

down-regulates activity

0.2

SRMS directly phosphorylates MKK4 and inhibits MKK4-JNK-c-Jun activation upon platinum treatment. Platinum treatment-induced ROS activates SRMS, which inhibits MKK4 kinase activity by directly phosphorylating MKK4 at Y269 and Y307, and consequently attenuates MKK4-JNK activation.

SIGNOR-277902

P31751

P49815

1

phosphorylation

down-regulates

0.729

We demonstrate here that tuberin is phosphorylated on s939 and t1462 in response to pi3k activation. Our results are consistent with akt being the pi3k-depen-dent tuberin kinase. The pi3k-akt-mediated phosphorylation of tuberin would inhibit the function of the tuberin-hamartin complex.

SIGNOR-91041

O15525

P27361

0

phosphorylation

up-regulates quantity

0.368

By contrast, MAFG-S124A was not phosphorylated, indicating that ERK1 phosphorylates MAFG at S124.|Notably, cotransfection of ERK1 increased total levels of wild-type MAFG and MAFG-T3A but not MAFG-S124A, indicating that phosphorylation increased MAFG stability.

SIGNOR-280027

P24941

P15172

1

phosphorylation

down-regulates

0.522

Cyclin e/cdk2 can phosphorylate myod at serine 200, which causes ubiquitination and degradation of this transcription factor during g1, preventing its accumulation and a commitment to differentiation.

SIGNOR-176509

P04637

Q96EB6

0

deacetylation

down-regulates

0.803

Sirt1 has been shown to regulate cell fate in part by deacetylating the p53 protein at lysine 382 and inhibiting p53-mediated transcriptional activation and apoptosis.

SIGNOR-182515

Q6ZN44

Q9HB63

2

binding

up-regulates

0.61

The unc5hs are axon guidance receptors that mediate netrin-1-dependent chemorepulsion, and dependence receptors that mediate netrin-1-independent apoptosis.

SIGNOR-98483

P12830

Q5T0T0

0

ubiquitination

down-regulates quantity by destabilization

0.2

Inhibiting proteasome activity with MG132 prevented CDH1 and beta2M degradation, indicating that MARCH8 might be targeting CDH1 and beta2M for proteasomal degradation.|We demonstrated that MARCH8 interacts with and ubiquitinates CDH1 and beta2M.

SIGNOR-278820

P17612

Q8N5S9

1

phosphorylation

down-regulates activity

0.2

In vitro, CaMKK is phosphorylated by PKA and this is associated with inhibition of enzyme activity. The major site of phosphorylation is threonine 108, although additional sites are phosphorylated with lower efficiency.

SIGNOR-256115

Q00535

O60229

1

phosphorylation

up-regulates activity

0.4

We then demonstrated that Cdk5 phosphorylates Kalirin 7 on Thr 1590 , increasing its GEF activity slightly and changing its solubility properties.

SIGNOR-279603

P01106

P61244

2

binding

up-regulates

0.743

In vivo transactivation assays suggest that myc-max and mad-max complexes have opposing functions in transcription and that max plays a central role in this network of transcription factors

SIGNOR-39137

P42772

Q8IXJ9

0

transcriptional regulation

up-regulates quantity by expression

0.276

Tumor suppressor ASXL1 is essential for the activation of INK4B expression in response to oncogene activity and anti-proliferative signals

SIGNOR-241759

Q9UIJ5

P78352

1

palmitoylation

up-regulates activity

0.379

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

SIGNOR-261290

Q00610

Q676U5

2

binding

up-regulates

0.46

Clathrin heavy-chain interacts with atg16l1, and is involved in the formation of atg16l1-positive early autophagosome precursors.

SIGNOR-166702

P20701

Q99996

2

binding

up-regulates activity

0.2

However, association of CG-NAP/AKAP450 was signifi-cantly enhanced at 37°C in LFA-1-activated cells triggered toundergo motility. Taken together, our findings provide the first definitiveevidence that the protein CG-NAP/AKAP450 is a key scaffoldingcomponent of the multimolecular complex assembled in T cellsupon LFA cross-linking and is functionally indispensable for cellpolarity and migration induced by this integrin.

SIGNOR-260304

P52797

P29317

2

binding

up-regulates

0.814

The eph family of receptors.

SIGNOR-52309

Q9ULJ6

P01106

1

transcriptional regulation

up-regulates quantity by expression

0.362

The N-terminal domain (NTD) of Zmiz1 is important for driving Myc transcription and proliferation […] Zmiz1 directly interacted with Notch1 via a tetratricopeptide repeat domain at a special class of Notch-regulatory sites.

SIGNOR-263939

P08151

Q9UMX1

2

binding

down-regulates activity

0.949

Here we characterize structural and functional determinants of Su(fu) required for Gli regulation and show that Su(fu) contains at least two distinct domains: a highly conserved carboxy-terminal region required for binding to the amino-terminal ends of the Gli proteins and a unique amino-terminal domain that binds the carboxy-terminal tail of Gli1. While each domain is capable of binding to different Gli1 regions independently, interactions between Su(fu) and Gli1 at both sites are required for cytoplasmic tethering and repression of Gli1

SIGNOR-249591

O14686

P23759

2

binding

up-regulates

0.304

Carm1 specifically methylates multiple arginines in the n-terminus of pax7. Methylated pax7 directly binds the c-terminal cleavage forms of the trithorax proteins mll1/2 resulting in the recruitment of the ash2l:mll1/2:wdr5:rbbp5 histone h3k4 methyltransferase complex to regulatory enhancers and the proximal promoter of myf5.

SIGNOR-198629

Q9Y490

Q05397

2

binding

up-regulates activity

0.688

Focal adhesion kinase (FAK) is activated by growth factors and integrins during migration, and functions as a receptor-proximal regulator of cell motility. At contacts between cells and the extracellular matrix, FAK functions as an adaptor protein to recruit other focal contact proteins or their regulators, which affects the assembly or disassembly of focal contacts. Whereas it was first hypothesized that FAK might bind directly to the cytoplasmic tails of integrins, accumulated evidence supports an indirect association of FAK with integrins through binding to integrin-associated proteins such as paxillin and talin.

SIGNOR-257731

Q9BUF5

Q14980

2

binding

up-regulates

0.2

Direct binding of numa to tubulin is mediated by a novel sequence motif in the tail domain that bundles and stabilizes microtubules.

SIGNOR-117109

P49841

Q9Y4K4

0

phosphorylation

down-regulates

0.2

Gckr can phosphorylate an n-terminal recombinant fusion protein of gsk3_ and enhance the in vivo phosphorylation of gsk3_ on serine 9reduction of gckr expression inhibits wnt3a-induced phosphorylation of gsk3_ at serine 9 and decreases the accumulation of cytosolic _-catenin.

SIGNOR-148908

Q13131

P35638

1

phosphorylation

down-regulates activity

0.265

Here, we report that phosphorylation of CHOP at Ser30 by AMPKα1 triggers CHOP degradation resulting in reduced macrophage apoptosis and subsequent ameliorated plaque vulnerability in vivo.

SIGNOR-259864

P42224

Q02763

0

phosphorylation

up-regulates activity

0.301

Tie2-R849W induced STAT1 phosphorylation at Y701 independent of ligand stimulation.|Together, Tie2-R849W induced functional activation of STAT1, leading to increased expression of STAT1-responsive gene like IRF1.

SIGNOR-279131

P42224

P52630

2

binding

up-regulates activity

0.555

We then examined STAT2 acetylation within the b-barrel DBD. A direct interaction between the STAT2-DBD (315485) and STAT1 was detected (Figure 6E) (Li et al., 1997).

SIGNOR-217957

P17542

Q02750

0

phosphorylation

down-regulates

0.2

We found that hypoxia greatly accelerated tal1 turnover in these cells through mitogen-activated protein kinase (mapk)2-mediated phosphorylation, ubiquitination, and proteasomal degradation.

SIGNOR-116149

P10415

P28482

0

phosphorylation

up-regulates quantity by stabilization

0.552

Phosphorylation of the map kinase sites in bcl-2, thr56, thr74, and ser87, is sufficient to inhibit tnf--induced degradation.

SIGNOR-74931

P21918

P19086

2

binding

up-regulates activity

0.404

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-257311

P10636

P48730

0

phosphorylation

down-regulates

0.374

Casein kinase 1 delta phosphorylates tau and disrupts its binding to microtubules.Here we characterized the contribution of one ck1 isoform, ckidelta, to the phosphorylation of tau at residues ser202/thr205 and ser396/ser404 in human embryonic kidney 293 cells.

SIGNOR-121717

Q04725

Q9UJU2

2

binding

down-regulates

0.638

Mapping studies reveal that groucho/tle binds two regions in lef-1.

SIGNOR-185736

P17252

P13498

1

phosphorylation

up-regulates

0.2

Phosphorylation of p22phox on threonine 147 enhances NADPH oxidase activity by promoting p47phox binding. | Threonine 147 of p22phox Is Phosphorylated by PKC-α and PKC-δ in Vitro

SIGNOR-260891

Q14653

Q7Z434

2

binding

up-regulates activity

0.8

Phosphorylated MAVS and STING then bind to a positively charged surface of interferon regulatory factor 3 (IRF3) and thereby recruit IRF3 for its phosphorylation and activation by TBK1.

SIGNOR-260143

Q96T68

P84243

1

methylation

up-regulates activity

0.2

Here, we have characterized a previously undescribed member of the histone H3K9 methyltransferase family named CLLD8 (or SETDB2 or KMT1F). This protein contributes to the trimethylation of both interspersed repetitive elements and centromere-associated repeats and participates in the recruitment of heterochromatin protein 1 to centromeres. Methylation of histone H3 at lysine 9 (H3K9) has emerged as an important player in the formation of heterochromatin, chromatin condensation, and transcriptional repression.

SIGNOR-263894

P18509

P41586

2

binding

up-regulates

0.877

Type i pacap receptors bind pacap-27 and -38. the potencies of the two forms of pacap are similar for adenylate cyclase stimulation, whereas pacap-38 is more potent than pacap-27 in phospholipase c activation.

SIGNOR-43225

P00519

Q14498

1

phosphorylation

up-regulates activity

0.322

In this paper, we report that RBM39 interacts with the nonreceptor tyrosine kinase c-Abl. Both the Src homology (SH) 2 and SH3 domains of c-Abl interact with RBM39. The major tyrosine phosphorylation sites on RBM39 that are phosphorylated by c-Abl are Y95 and Y99, as demonstrated by liquid chromatography coupled with tandem mass spectrometry (LC/MS/MS) and mutational analysis. c-Abl was shown boost the transcriptional coactivation activity of RBM39 for ERα and PRβ in a tyrosine kinase-dependent manner.

SIGNOR-262609

P23588

P60842

2

binding

up-regulates activity

0.867

Either eIF4B or eIF4H stimulated the initial rate and amplitude of eIF4A-dependent duplex unwinding, and the magnitude of stimulation is dependent on duplex stability

SIGNOR-261293

Q13526

Q15468

2

binding

up-regulates

0.361

Cell cycle-dependent phosphorylation of sil is required for its interaction with pin1, a regulator of mitosis. Point mutation of the seven (s/t)p sites between amino acids 567 and 760 reduces mitotic phosphorylation of sil, pin1 binding, and spindle checkpoint duration.

SIGNOR-138677

Q53ET0

P04150

2

binding

up-regulates activity

0.294

We show here that CRTC2 also functions as a coactivator for the glucocorticoid receptor (GR).

SIGNOR-256101

P17987

P36508

0

transcriptional regulation

up-regulates quantity by expression

0.347

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

SIGNOR-266221

O15516

Q7Z5J4

0

transcriptional regulation

up-regulates quantity by expression

0.479

RAI1 Transcriptionally Activates CLOCK via an Intron 1 Enhancer Element. data suggest that RAI1 binds, directly or in a complex, to the first intron of CLOCK and enhances its transcriptional activity in vitro, supporting RAI1 as a positive regulator of CLOCK and an important part of the circadian loop of transcription. Data further show that haploinsufficiency of RAI1 and Rai1 in SMS fibroblasts and the mouse hypothalamus, respectively, results in the transcriptional dysregulation of the circadian clock and causes altered expression and regulation of multiple circadian genes, including PER2, PER3, CRY1, BMAL1, and others.

SIGNOR-266839

P49761

P01106

0

transcriptional regulation

up-regulates quantity by expression

0.2

C-Myc enhances transcriptional activation of CLK3 promoter in CCA cells.

SIGNOR-274123

Q96CN5

Q68D86

2

binding

up-regulates activity

0.2

CCDC102B is recruited to the centrosome by C-Nap1 (also known as CEP250) and interacts with the centrosome linker components rootletin and LRRC45. CCDC102B decorates and facilitates the formation of rootletin filaments. Furthermore, CCDC102B is phosphorylated by Nek2A (an isoform encoded by NEK2) and is disassociated from the centrosome at the onset of mitosis.

SIGNOR-275627

Q6JBY9

P53778

0

phosphorylation

down-regulates activity

0.504

Peptide T2 was sequenced and shown to comprise residues 79–112 of CapZIP, phosphorylated at Ser-108 (Figure 2B). The identity of peptide T1 is unknown. These experiments established that the SAPK3/p38γ substrate was CapZIP. Using this antibody, we showed by immunoblotting that bacterially expressed CapZIP was phosphorylated at Ser-108 by SAPK4/p38δ, JNK1α1 and ERK2 in vitro, as well as by SAPK3/p38γ (results not shown). An important clue to the function of CapZIP and its phosphorylation came from the finding that it binds to the actin-capping protein CapZ (Figure 7A), and that cellular stresses trigger the dissociation of these two proteins (Figure 7B).Such an effect is presumably lost when CapZIP is phosphorylated and dissociates from CapZ.

SIGNOR-263083

P19484

P11802

0

phosphorylation

up-regulates activity

0.2

CDK4 and CDK6 phosphorylate TFEB and TFE3.

SIGNOR-279450

Q12913

P28482

1

dephosphorylation

down-regulates

0.406

In this study we show that one of these potential targets, the erk1/2, is indeed a direct dep-1 substrate in vivo.

SIGNOR-161536

P04637

Q00653

2

binding

up-regulates

0.425

P52 cooperates with p53 to regulate other known p53 target genes.

SIGNOR-149811

P63092

P08588

2

binding

up-regulates activity

0.527

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-256758

A1L390

P60953

1

guanine nucleotide exchange factor

up-regulates activity

0.354

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-260585

Q03113

P28335

2

binding

up-regulates activity

0.277

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-257405

P17612

P17752

1

phosphorylation

up-regulates activity

0.35

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

SIGNOR-250062

P38398

Q00341

2

binding

up-regulates activity

0.2

We show that vigilin interacts with the DNA damage response (DDR) proteins RAD51 and BRCA1, and vigilin depletion impairs their recruitment to DSB sites.

SIGNOR-266698

Q13351

P68400

0

phosphorylation

up-regulates activity

0.344

Regulation of erythroid Krppel-like factor (EKLF) transcriptional activity by phosphorylation of a protein kinase casein kinase II site within its interaction domain. the transactivation capability of EKLF is augmented by co-transfection of CKIIalpha. in vitro assays demonstrate that CKIIalpha interacts with EKLF, and that the EKLF interaction domain is phosphorylated by CKII only at Thr-41

SIGNOR-241361

O76064

Q969R5

1

ubiquitination

up-regulates activity

0.242

L3MBTL2 links RNF8 and RNF168 in the DNA double strand break response. The protein kinase ATM phosphorylates L3MBTL2, which recruits it to the DNA lesion by promoting the interaction between MDC1 and L3MBTL2. L3MBTL2 is subsequently ubiquitinated by RNF8, which acts as a docking site for RNF168, thereby recruiting the ubiquitin ligase to the damage site. RNF168, in turn, ubiquitinates H2A-type histones to amplify the DNA damage response and recruit downstream DNA repair proteins for proper DSB signaling.

SIGNOR-266787

P27361

Q9UIG0

1

phosphorylation

up-regulates

0.2

Wstf, a specific component of two chromatin remodeling complexes (swi/snf-type winac and iswi-type wich), was phosphorylated by the stimulation of mapk cascades in vitro and in vivo. Ser-158 residue in the wac (wstf/acf1/cbpq46) domain, located close to the n terminus of wstf, was identified as a major phosphorylation target

SIGNOR-188164