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
P00533	Q32MZ4	0	transcriptional regulation	down-regulates quantity by repression	0.293	GC-binding factor 2 (GCF2) is a transcriptional repressor that decreases activity of the epidermal growth factor receptor (EGFR) and other genes. \|Deletion mutants of GCF2 revealed that amino acids 429–528 are required for both DNA binding and repression of the EGFR promoter.	SIGNOR-266057
Q13535	Q99708	1	phosphorylation	up-regulates	0.615	Characterization of this site using phospho-specific antibodies and mutational analysis reveals that it is phosphorylated by atr and is required for binding of ctip to chromatin and subsequent processive resection.	SIGNOR-200245
Q15818	Q07812	1	relocalization	up-regulates activity	0.2	Immunofluorescence staining and subcellular fractionation analyses revealed increased mitochondrial translocation of Bad and Bax proteins from cytoplasm following OGD (4 h) and simultaneously increased release of Cyt C from mitochondria followed by activation of caspase-3. NP1 protein was immunoprecipitated with Bad and Bax proteins; OGD caused increased interactions of NP1 with Bad and Bax, thereby, facilitating their mitochondrial translocation and dissipation of mitochondrial membrane potential	SIGNOR-261439
Q08117	Q96QT6	2	binding	up-regulates activity	0.2	We have cloned and characterized a new member of the PHD zinc finger family called Pf1 that interacts with two global transcription corepressors: mSin3A and TLE. Pf1 interacts with TLE. The Groucho/TLE proteins are members of an abundant corepressor family, and we hypothesized that Pf1 might interact with TLE family members. Together, these data suggest that in the absence of interactions with mSin3A, Gal4-Pf1 (102–273 L212P/A216P)-dependent repression can be attributed to interaction with endogenous TLE.	SIGNOR-266990
P15172	Q8IXJ6	0	deacetylation	down-regulates	0.376	Sir2-mediated deacetylation of myod can be expected to inhibit its transcriptional capabilities.	SIGNOR-104251
P01106	P49840	0	phosphorylation	down-regulates quantity by destabilization	0.406	Similar to c-myc, similar to c-myc, we report here that phosphorylation of c-jun by gsk3 creates a high-affinity binding site for the e3 ligase fbw7, which targets c-jun for polyubiquitination and proteasomal degradation.	SIGNOR-138596
P17612	O14965	1	phosphorylation	up-regulates activity	0.512	Aurora2 is regulated by phosphorylation. phosphorylation occurs on a conserved residue, Threonine 288, within the activation loop of the catalytic domain of the kinase and results in a significant increase in the enzymatic activity. Threonine 288 resides within a consensus motif for the cAMP dependent kinase and can be phosphorylated by PKA in vitro.	SIGNOR-250337
P15151	Q15762	2	binding	up-regulates activity	0.82	We focused on receptor-ligand interactions between CAFs and NK cell and found that cell-surface poliovirus receptor (PVR/CD155), a ligand of activating NK receptor DNAM-1, was downregulated in the CAFs compared with NEFs. \|Poliovirus receptor (PVR/CD155) is a ligand of the paired NK receptors, DNAM-1 (activating) and TIGIT (inhibiting). NK cells can kill cancer cells expressing PVR via the DNAM-1-mediated activating signaling (11,12).	SIGNOR-261424
O43236	O60260	0	ubiquitination	down-regulates quantity by destabilization	0.2	Thus, Parkin degrades ARTS in a proteasome dependent manner.\|Together, these results suggest that Parkin specifically ubiquitinates and degrades ARTS, and that this degradation may be linked to the pro-apoptotic function of ARTS.	SIGNOR-278642
O14921	P17612	0	phosphorylation	up-regulates quantity by stabilization	0.334	Phosphorylation of RGS13 by the cyclic AMP-dependent protein kinase inhibits RGS13 degradation.we show that PKA activation also leads to increased steady-state RGS13 expression through RGS13 phosphorylation, which inhibits RGS13 protein degradation. RGS13 phosphorylation was diminished by mutation of an N-terminal Thr residue (T41) identified as a phosphorylation site by mass spectrometry.	SIGNOR-259835
Q08050	O14757	0	phosphorylation	up-regulates activity	0.371	In addition, upon treatment with genotoxic agents, the checkpoint kinases Chk1 and Chk2 also phosphorylate and activate FOXM1.	SIGNOR-280224
Q15172	P36897	2	binding	up-regulates	0.261	In this report, we show that another wd-40 repeat protein, the balpha subunit of protein phosphatase 2a, associates with the cytoplasmic domain of type i tgf-beta receptors..[..] Furthermore, balpha enhances the growth inhibition activity of tgf-beta in a receptor-dependent manner	SIGNOR-60743
Q08881	P19174	1	phosphorylation	up-regulates	0.637	In t cells, the predominant tec kinase is itk, which functions downstream of the t-cell receptor to regulate phospholipase c-gamma.	SIGNOR-165803
P54762	Q969H4	2	binding	up-regulates activity	0.293	The phosphorylated CNK1 interacts with ephrinB1. The binding of ephrinB1 to CNK1 connects RhoA and p115RhoGEF with ephrinB1-associated MKK4, promoting JNK activation and cell migration.	SIGNOR-275921
Q9UHN6	Q86YJ5	0	ubiquitination	down-regulates quantity by destabilization	0.2	MARCH9, a member of the RING-CH family of transmembrane E3 ubiquitin ligases, down-regulates CD4, major histocompatibility complex-I (MHC), and ICAM-1 in lymphoid cells. To identify novel MARCH9 substrates, we used high throughput flow cytometry and quantitative mass spectrometry by stable isotope labeling by amino acids in cell culture (SILAC) to determine the differential expression of plasma membrane proteins in a MARCH9-expressing B cell line. This combined approach identified 13 potential new MARCH9 targets.	SIGNOR-271533
P12931	P50402	1	phosphorylation	down-regulates	0.451	Src phosphorylated emerin specifically at y59, y74 and y95; interestingly y-to-f substitutions at identified src sites reduced recombinant emerin binding to endogenous baf	SIGNOR-188308
P12931	Q9Y4K3	1	phosphorylation	up-regulates activity	0.565	To gain further insights into the molecular mechanisms, we employed mass spectrometry to identify the specific tyrosine residues of Traf6 that are phosphorylated by c-Src.By mutating these phosphorylation sites to phenylalanine, we disrupted Traf6-mediated polyubiquitination and subsequently observed the inactivation of AEP. This finding suggests that the phosphorylation of Traf6 by c-Src is crucial for AEP activation.	SIGNOR-277866
P38936	Q15831	0	phosphorylation	down-regulates activity	0.488	Mass spectrometry analysis of the phosphorylated CDKN1A identified Thr80 as the residue phosphorylated by LKB1 in vitro (Figure 4A and S5A).\|UVB induced phosphorylation of LKB1 T366 mediates CDKN1A degradation.	SIGNOR-278253
Q92633	P50148	2	binding	up-regulates activity	0.544	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-257091
P04792	Q13237	0	phosphorylation	down-regulates	0.2	Purified pkg isoforms ia, ib, and ii all caused incorporation of phosphate in recombinant hsp27 at ser-78, ser-82, and thr-143, but not ser-15.These Studies indicate that hsp27 is a genuine substrate for pkg and that pkg may mediate inhibition of platelet aggregation through phosphorylation of hsp27 and subsequent prevent of actin polymerization	SIGNOR-186947
Q9NQW6	Q9UM11	2	binding	down-regulates quantity by destabilization	0.265	Ubiquitination of anillin required a destruction-box and was mediated by Cdh1, an activator of APC/C. Overexpression of Cdh1 reduced the levels of anillin, whereas inactivation of APC/C(Cdh1) increased the half-life of anillin.	SIGNOR-272654
Q9UKX2	P14859	0	transcriptional regulation	up-regulates quantity by expression	0.2	Myocyte enhancer factor-2 and serum response factor binding elements regulate fast Myosin heavy chain transcription in vivo. We show that the upstream promoter region of the gene most abundantly expressed in mouse skeletal muscles, IIb MyHC, retains binding activity and transcriptional activation for three positive transcription factors, the serum response factor, Oct-1, and myocyte enhancer factor-2, whereas the other two genes (IIa and IId/x) have nucleotide substitutions in these sites that reduce binding and transcriptional activation	SIGNOR-238757
P50148	P30968	2	binding	up-regulates activity	0.474	Here we systematically quantified ligand-induced interactions between 148 GPCRs and all 11 unique G alpha subunit C-termini. For each receptor, we probed chimeric G alpha subunit activation via a transforming growth factor-alpha (TGF alpha) shedding response in HEK293 cells lacking endogenous Gq/11- and G12/13- signaling. \| We defined positive coupling if any member of the subfamily scored LogRAi ≥ -1 and negative coupling if all of the members scored LogRAi < -1 (Figure 3A-B). ROC analysis gives AUC = 0.78 (Figure S4A) when considering high-confidence known coupling data and suggested a threshold of LogRAi ≥ -1.0 for defining true couplings. \| The score associated to this interaction has a LogRAi ≥ -1.0.	SIGNOR-257265
Q14344	Q9UBY5	2	binding	up-regulates	0.4	Serum-borne lysophosphatidic acid (lpa) and sphingosine 1-phosphophate (s1p) act through g12/13-coupled receptors to inhibit the hippo pathway kinases lats1/2 thereby activating yap and taz transcription co-activators, which are oncoproteins repressed by lats1/2.	SIGNOR-198547
P52630	P29597	0	phosphorylation	up-regulates activity	0.789	JAK1 and TYK2 will phosphorylate and activate STAT1 and STAT2 respectively, leading to the formation of the ternary interferon-stimulated gene factor 3 (ISGF3) complex, composed of STAT1, STAT2 and interferon regulatory factor 9 (IRF9).	SIGNOR-279133
P22681	P27986	1	ubiquitination	down-regulates	0.694	Cbl-b, a ring-type e3 ubiquitin protein ligase, is implicated in setting the threshold of t lymphocyte activation. The p85 regulatory subunit of phosphatidylinositol 3 kinase (pi3k) was identified as a substrate for cbl-b. We have shown that cbl-b negatively regulated p85 in a proteolysis-independent manner.	SIGNOR-110060
P01266	P07202	0	catalytic activity	up-regulates activity	0.505	After transport through the apical membrane, I− is covalently bound to the tyrosyl residues of Tg by thyroid peroxidase (TPO).	SIGNOR-259914
Q8IW41	Q15382	1	phosphorylation	down-regulates activity	0.401	Phosphorylation of Rheb at Ser 130 by PRAK impairs the nucleotide-binding ability of Rheb and inhibits Rheb-mediated mTORC1 activation.	SIGNOR-276313
Q8N0Z6	Q09472	2	binding	up-regulates activity	0.563	DNA damage activates ATM kinase which then phosphorylates Strap at Ser 203 (red circles). Phosphorylated Strap is stabilized and undergoes nuclear accumulation where it assembles into a co-activator complex, which includes p300 and cofactors such as JMY	SIGNOR-262646
P98177	P24941	0	phosphorylation	down-regulates	0.518	Additionally, ck1, dyrk1a, and cdk2 also phosphorylate foxos at various sites to inhibit foxos activity	SIGNOR-183655
P40189	Q16619	2	binding	up-regulates	0.627	In the cos-7 cell line demonstrate that gp130-gp190 heterocomplex formation is essential for ct-1 signaling	SIGNOR-46509
Q16620	Q92529	2	binding	up-regulates	0.755	Our present study established that n-shc and sck are expressed in a region-specific manner in the brain and that n-shc is a higher affinity adapter molecule than sck for trka and trkb receptors	SIGNOR-55864
O95714	Q96JN8	1	polyubiquitination	down-regulates quantity by destabilization	0.456	NEURL4 is a substrate of HERC2, and together these results indicate that the NEURL4-HERC2 complex participates in the ubiquitin-dependent regulation of centrosome architecture.	SIGNOR-272921
Q9BUB5	P06730	1	phosphorylation	up-regulates	0.779	Mnk1 and mnk2 regulate protein synthesis by phosphorylating the initiation factor eif4e.	SIGNOR-166646
P29350	P06239	2	dephosphorylation	down-regulates activity	0.613	We demonstrate that shp-1 dephosphorylates the lymphoid-specific src family kinase lck at tyr-394. Because phosphorylation of tyr-394 activates lck, the fact that shp-1 specifically dephosphorylates this site suggests that shp-1 is a negative regulator of lck.	SIGNOR-106604
Q9BXK1	P12931	0	phosphorylation	up-regulates activity	0.245	We further confirmed that the Tyr-10 residue of KLF16 is phosphorylated in uterine cells (Fig. 7c). Additional experiments using both pharmacological and dominant negative inhibitors of Src further supported a role for this tyrosine kinase in modulating the activity of KLF16 (Fig. 7, d and f).	SIGNOR-276398
P49841	P08581	0	phosphorylation	up-regulates activity	0.308	MET phosphorylated and activated GSK3B at tyrosine 56, which decreased the expression of PDL1 by liver cancer cells.	SIGNOR-277428
Q9BQE3	Q14980	2	binding	up-regulates	0.258	Direct binding of numa to tubulin is mediated by a novel sequence motif in the tail domain that bundles and stabilizes microtubules.	SIGNOR-116677
O15519	P05771	0	phosphorylation	up-regulates quantity by stabilization	0.2	Here, we identify serine 193 as a novel in vivo phosphorylation site of all c-FLIP proteins. c-FLIP S193 phosphorylation is mediated by PKCa and PKCb.S193 phosphorylation increases the stability of the short c-FLIP proteins	SIGNOR-276146
P19105	P53355	0	phosphorylation	up-regulates activity	0.275	DAPK Phosphorylates Myosin II RLC in Vitro and in Vivo. Together these results show that similar to the conventional MLCKs, Ser-19 is the primary RLC residue phosphorylated by DAPK and that phosphorylation of Thr-18 is also possible.	SIGNOR-262842
P49841	P10275	1	phosphorylation	down-regulates activity	0.649	Glycogen synthase kinase-3 beta is involved in the phosphorylation and suppression of androgen receptor activity.\|In particular, we showed that glycogen synthase kinase-3 beta phosphorylates the androgen receptor, thereby inhibiting androgen receptor-driven transcription.	SIGNOR-279334
O15169	P36873	0	dephosphorylation	down-regulates activity	0.269	The data suggest that PP1 controls Wnt signaling through interaction with, and regulated dephosphorylation of, axin\| Axin phosphorylation markedly enhances the binding of glycogen synthase kinase 3, leading to a more active beta-catenin destruction complex. Wnt-regulated changes in axin phosphorylation, mediated by PP1, may therefore determine beta-catenin transcriptional activity\| Four sites, S80, S82, S222, and S473, were identified to be PP1 regulated	SIGNOR-248494
P50750	P50613	0	phosphorylation	up-regulates activity	0.551	Cdk7 activates Cdk9 in vitro .\|Cdk7 phosphorylates wild-type Cdk9 on Thr186, resulting in increased activity towards a recombinant GST-Spt5 substrate.	SIGNOR-279455
Q13362	P27361	2	binding	down-regulates	0.42	B56-containing pp2a dephosphorylate erk and their activity is controlled by the early gene iex-1 and erk	SIGNOR-144328
P27986	P06239	0	phosphorylation	down-regulates activity	0.623	the regulatory p85 subunit of phosphatidylinositol 3-kinase is phosphorylated on tyrosine residues. We report that this phosphorylation event is readily catalyzed by the Abl and Lck protein-tyrosine kinases in vitro, by Bcr-Abl or a catalytically activated Lck-Y505F in co-transfected COS cells. we have mapped a major phosphorylation site to Tyr-688 in the C-terminal SH2 domain of p85. Tyrosine phosphorylation of p85 in vitro or in vivo was not associated with detectable change in the enzymatic activity of the phosphatidylinositol 3-kinase heterodimer, but correlated with a strong reduction in the binding of some, but not all, phosphoproteins to the SH2 domains of p85.	SIGNOR-251383
P63096	P30411	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-256695
P04792	Q13976	0	phosphorylation	down-regulates	0.274	Purified pkg isoforms ia, ib, and ii all caused incorporation of phosphate in recombinant hsp27 at ser-78, ser-82, and thr-143, but not ser-15.These Studies indicate that hsp27 is a genuine substrate for pkg and that pkg may mediate inhibition of platelet aggregation through phosphorylation of hsp27 and subsequent prevent of actin polymerization	SIGNOR-186784
P05412	P68400	0	phosphorylation	down-regulates	0.592	Casein kinase ii is a negative regulator of c-jun dna binding and ap-1 activitywe show that two of these sites, thr-231 and ser-249, are phosphorylated by casein kinase ii (ckii).	SIGNOR-19607
P42336	P63211	2	binding	up-regulates	0.432	Gbetagamma subunits released from gi can activate pi3k (phosphoinositide 3-kinase), and can be therefore implicated in smo-dependent activation of akt	SIGNOR-154261
Q9NQ66	O95837	2	binding	up-regulates activity	0.468	This suggests that both Gal4 and Gal6 can activate PLC b1.	SIGNOR-278119
P28482	P49137	1	phosphorylation	up-regulates	0.507	Using novel methodology we demonstrate that activation of mapkap kinase-2 requires the phosphorylation of any two of the three residues thr222, ser272 and thr334. gst-mapkap kinase-2 lacking the n-terminal domain was inactive, but activated fully when phosphorylated at thr222, ser272 and thr334 by p42 mapk or rk.	SIGNOR-44343
O15354	O60260	0	ubiquitination	down-regulates quantity by destabilization	0.2	Parkin is a protein of 465 amino acids, and its structure includes a ubiquitin homologous domain in its N terminus and two RING finger domains in its C terminus. Molecular studies have determined that parkin is an E3 ubiquitin ligase function, implicating parkin in the ubiquitin-proteasome system, and raising the possibility that mutations in the gene lead to loss or diminished function. Three substrates for the ubiquitin-ligase function of parkin have been identified to date.1. A 22kDa glycosolated form of alpha-synuclei\|2. Parkin-associated endothelin receptor-like receptor (Pael-R).	SIGNOR-249706
O00192	Q96RT1	2	binding	up-regulates activity	0.2	We characterized the interactions between the Erbin PDZ domain and both ARVCF and δ-catenin in vitro and in vivo. endogenous δ-catenin and Erbin co-localized in and co-immunoprecipitated from neurons. These results suggest that δ-catenin and ARVCF may function to mediate the association of Erbin with the junctional cadherin-catenin complex.	SIGNOR-252119
P23396	P28482	0	phosphorylation	up-regulates	0.2	Erk phosphorylates threonine 42 residue of ribosomal protein s3.	SIGNOR-137955
Q05397	Q14680	0	phosphorylation	up-regulates activity	0.2	As the aforementioned results showed that MELK promotes FAK phosphorylation, and it is well known that FAK is an important regulator of cell migration and invasion, we speculated that MELK could regulate cell migration and invasion via the FAK/Paxillin pathway.\|Finally, knockdown of MELK decreased the phosphorylation of the FAK and paxillin, and prevented gastrin stimulated FAK and paxillin phosphorylation.	SIGNOR-279230
O14874	P12694	1	phosphorylation	down-regulates	0.609	Phosphorylation sites and inactivation of branched-chain alpha-ketoacid dehydrogenase isolated from rat heart, bovine kidney, and rabbit liver, kidney, heart, brain, and skeletal muscle.	SIGNOR-25084
O43318	Q15797	1	phosphorylation	up-regulates activity	0.373	This analysis showed that phosphorylation of Smad1 at the C-terminal serines S463 and S465 was increased by co-expression of constitutively active TAK1.	SIGNOR-279419
O75581	P56704	2	binding	up-regulates activity	0.79	Here, we present evidence that lrp6 is internalized with caveolin and that the components of this endocytic pathway are required not only for wnt-3a-induced internalization of lrp6 but also for accumulation of beta-catenin.	SIGNOR-148671
P41279	P45985	1	phosphorylation	up-regulates	0.559	Furthermore, we found that immunoprecipitated tpl-2 could directly phosphorylate and activate both mek-1 and mkk4 (also known as sek-1)	SIGNOR-196744
P27987	P17612	0	phosphorylation	down-regulates activity	0.351	Two isoforms of the inositol 1,4,5-trisphosphate 3-kinase have been identified, the A form and the B form. phosphorylation of isoform A by the cyclic AMP-dependent protein kinase increased activity 1.5-fold, whereas phosphorylation of isoform B decreased activity by 45%. major phosphorylation sites in the protein are Ser119 for PKA. Ser119 in the A isoform is conserved in the B isoform as Ser328	SIGNOR-249995
P61296	P61296	2	binding	up-regulates activity	0.2	The basic helix-loop-helix factor, HAND2, functions as a transcriptional activator by binding to E-boxes as a heterodimer	SIGNOR-223476
P26010	Q9Y490	2	binding	up-regulates activity	0.585	Over the past 10 years, the binding of talin to the cytoplasmic tail of integrin-β subunits has been established to have a key role in integrin activation. Binding of the phosphotyrosinebinding (PTB)-domain-like subdomain of the protein 4.1, ezrin, radixin, moesin (FERM) domain of talin to the conserved WxxxNP(I/L)Y motif of the β-integrin tail permits additional weaker interactions between talin and the membrane-proximal region of the tail that trigger integrin activation, probably through the disruption of inhibitory interactions between α- and β-subunit cytoplasmic tails.	SIGNOR-257633
P02679	P02751	2	binding	down-regulates activity	0.553	Fibrinogen y-chain carboxyterminal (GQQHHLGGAKQAGDV) peptides inhibit fibrinogen, fibronectin (Fn), vitronectin, and von Willebrand factor (vWF) binding to the platelet glycoprotein Ilb-Illa complex (GP lIbII1a).	SIGNOR-251970
Q13535	Q9BXW9	1	phosphorylation	up-regulates	0.673	In the present study, we identify two novel dna damage-inducible phosphorylation sites on fancd2, threonine 691 and serine 717. Atr phosphorylates fancd2 on these two sites, thereby promoting fancd2 monoubiquitination and enhancing cellular resistance to dna cross-linking agents	SIGNOR-149305
P52732	Q8TDX7	0	phosphorylation	up-regulates activity	0.407	NEK7 regulates these processes in part through phosphorylation of the kinesin Eg5/KIF11, promoting its accumulation on microtubules in distal dendrites.	SIGNOR-273890
Q9H0R8	Q13501	2	binding	up-regulates activity	0.79	P62 binds both to lc3a and -b and the related gabarap family proteins/this interaction is necessary for autophagic degradation of p62-positive cytoplasmic inclusion bodies containing ubiquitinated proteins. We also demonstrate that alis are indistinguisha	SIGNOR-156304
Q13501	P60520	2	binding	up-regulates activity	0.862	P62 binds both to lc3a and -b and the related gabarap family proteins/this interaction is necessary for autophagic degradation of p62-positive cytoplasmic inclusion bodies containing ubiquitinated proteins. We also demonstrate that alis are indistinguisha	SIGNOR-156307
P17676	P41440	1	transcriptional regulation	up-regulates quantity by expression	0.2	Collectively, these results identify transcriptionally important regions in the hRFC-C minimal promoter that include a GC-box and CCAAT-box, and suggest that cooperative interactions between Sp1 and C/EBP beta are essential for hRFC-C transactivation.	SIGNOR-254053
O75030	P63279	0	ubiquitination	down-regulates	0.565	Furthermore, we identified lysine 201 as a potential ubiquitination site. A lysine to arginine mutation abolished mitf (k201r) degradation by hubc9 in vivo.	SIGNOR-75117
P38398	Q15424	1	ubiquitination	up-regulates quantity by stabilization	0.2	These results suggest that the BRCA1 and BARD1 heterodimer ubiquitinates SAFB and increases SAFB protein levels.	SIGNOR-278624
Q92576	P24928	2	binding	down-regulates activity	0.46	PHF3 interacts with RNA polymerase II through the SPOC domain. PHF3 negatively regulates mRNA levels. Here, we identify PHD-finger protein 3 (PHF3) as a regulator of transcription and mRNA stability that docks onto Pol II CTD through its SPOC domain. Our data suggest that PHF3 acts as a prominent effector of neuronal gene regulation by bridging transcription with mRNA decay. PHF3 SPOC preferentially binds RNA Pol II CTD phosphorylated on Serine-2	SIGNOR-266965
Q13315	Q8N163	1	phosphorylation	up-regulates activity	0.587	Here, we report that, in human cell lines, DNA damage triggered the phosphorylation of DBC1 on Thr454 by ATM (ataxia telangiectasia-mutated) and ATR (ataxia telangiectasia and Rad3-related) kinases. Phosphorylated DBC1 bound to and inhibited SIRT1, resulting in the dissociation of the SIRT1-p53 complex and stimulating p53 acetylation and p53-dependent cell death.	SIGNOR-267661
Q99873	P48729	0	phosphorylation	up-regulates activity	0.2	CSNK1a1 directly bound and phosphorylated PRMT1 to control its genomic targeting to PRMT1-sustained proliferation genes as well as PRMT1-suppressed differentiation genes.\|Taken together, these data support a provisional model in which CSNK1a1 directs PRMT1 to genomic targets that promote self-renewal and suppress terminal differentiation.In the context of transcription regulation, PRMT1 has been generally considered as a transcriptional co-activator.	SIGNOR-279733
P12931	Q07954	1	phosphorylation	up-regulates activity	0.394	We recently observed that the ldl receptor-related protein 1 (lrp-1) is tyrosine phosphorylated in v-src-transformed cells.Of the four tyrosine residues present in the cytoplasmic domain of lrp-1, only tyr 63 is phosphorylated by v-src in vivo or in vitro. Using fibroblasts deficient in src, yes and fyn, we were able to show that there are multiple kinases present in the cell that can phosphorylate lrp-1. Tyrosine-phosphorylated lrp-1 associates with shc, a ptb and sh2 domain containing signaling protein that is involved in the activation of ras	SIGNOR-101535
P21802	P62993	1	phosphorylation	up-regulates	0.773	Inhibition of basal fgf receptor signaling by dimeric grb2.	SIGNOR-197980
P25963	O14965	0	phosphorylation	down-regulates activity	0.541	The results of the in vitro kinase assay, using purified human recombinant AURKA and IkappaBalpha proteins, confirmed that AURKA can directly phosphorylate IkappaBalpha (Ser32) at a concentration as low as 2.5 ng/mul (XREF_FIG).\|While an earlier study suggested that AURKA down-regulates IkappaBalpha indirectly through activation of the PI3K and AKT pathway 35, our data demonstrate, for the first time, that AURKA directly binds and phosphorylates the IkappaBalpha subunit, leading to activation of NF-kappaB.	SIGNOR-278912
P34972	P63096	2	binding	up-regulates activity	0.468	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-256700
P55085	P07477	0	cleavage	up-regulates activity	0.388	Mass spectrometry studies of PAR2E predicted activation of PAR2 by trypsin through cleavage at the Arg36-Ser37 site, no effect of thrombin, and inactivation of the receptor by plasmin, calpain and leukocyte elastase, cathepsin G, and proteinase 3.	SIGNOR-263602
Q9NPG1	P61586	2	binding	up-regulates activity	0.344	Upon ligand binding, non-canonical wnt signaling controls tissue polarity and cell movement through the activation of rhoa, c-jun n-terminal kinase (jnk), and nemo-like kinase (nlk) signaling cascades.	SIGNOR-167865
P51692	Q13882	0	phosphorylation	up-regulates	0.429	Phosphospecific antibodies, mutational analysis, and in vitro kinase assays demonstrated that brk specifically mediated stat5b phosphorylation at the activating tyrosine, y699.	SIGNOR-159066
P09471	Q9H1C0	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-256997
O60674	P15260	2	phosphorylation	up-regulates activity	0.714	In the classical model of IFNgamma signaling, dimeric IFNgamma cross-links the IFNGR1 receptor subunit that results in allosteric changes in receptor cytoplasmic domain. This results in movement of JAK2 from receptor subunit IFNGR2 to IFNGR1. The JAKs autophosphorylate and then phosphorylate IFNGR1 cytoplasmic domain. This results in binding, phosphorylation, and dimer formation of STAT1_. The dimeric STAT1_ dissociates from receptor and undergoes nuclear translocation via an intrinsic NLS for specific gene activation	SIGNOR-249490
P42684	P04040	1	phosphorylation	up-regulates activity	0.34	C-abl and arg phosphorylated catalase at tyr231 and tyr386 in vitrocatalase is a major effector in the defense of aerobic cells against oxidative stress. Recent studies have shown that catalase activity is stimulated by the c-abl and arg tyrosine kinases	SIGNOR-101306
Q8N6T3	Q5S007	2	binding	up-regulates	0.579	The gtp hydrolysis activity of lrrk2 is markedly enhanced by arfgap1 supporting a role for arfgap1 as a gtpase-activating protein for lrrk2.Lrrk2 and arfgap1 interact in vitro in mammalian cells and in vivo in brain, and co-localize in the cytoplasm and at golgi membranes	SIGNOR-196264
P09467	P17010	0	transcriptional regulation	down-regulates quantity by repression	0.2	For instance, nucleophosmin (NPM1) and zinc-finger protein X-linked (ZFX) bind to the E-box and ZFX binding site on the FBP1 promoter, respectively, and restrain FBP1 expression to facilitate aerobic glycolysis in PDAC and melanoma	SIGNOR-267595
Q9UHD0	Q6UXL0	2	binding	up-regulates	0.719	Il-19 signals only through the type i il-20r complex.	SIGNOR-151820
P09471	Q9GZQ4	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 ≥ -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-257010
Q16143	Q9NYY3	0	phosphorylation	down-regulates activity	0.248	Polo-like kinase (plk) family (plk1, plk2, and plk3) phosphorylate alpha-syn and beta-syn specifically at ser-129 and ser-118, respectively. Polo-like kinase 2 (plk2) phosphorylates alpha-synuclein at serine 129 in central nervous system. The membrane association of pd-linked mutant alpha -synuclein, but not wild-type -synuclein, was increased by serine 129 phosphorylation.	SIGNOR-189049
P0CG47	Q96BN8	0	cleavage	up-regulates quantity	0.671	Here we provide data suggesting that two of the four mammalian ubiquitin precursors, UBA52 and UBA80, are processed mostly post-translationally whereas the other two, UBB and UBC, probably undergo a combination of co- and post-translational processing. Using an unbiased biochemical approach we found that UCHL3, USP9X, USP7, USP5 and Otulin/Gumby/FAM105b are by far the most active DUBs acting on these precursors.	SIGNOR-270819
O14745	P43250	0	phosphorylation	down-regulates activity	0.405	GRK6A phosphorylates NHERF on Ser289, the primary site of constitutive phosphorylation of NHERF in HEK-293 cells. The interaction of NHERF and NHE3 is mediated by the region of NHERF encompassing the second PDZ domain and the tail (25), and it is therefore reasonable that phosphorylation of the serine-rich stretch in the center of this region (including Ser289) might affect the physical interaction of NHERF with NHE3.	SIGNOR-251214
P09211	Q02156	0	phosphorylation	up-regulates activity	0.2	Peptide phosphorylation analyses and both phosphorylation and enzyme kinetic studies with GSTP1 proteins mutated at candidate amino acid residues established Ser-42 and Ser-184 as putative phospho-acceptor residues for both kinases in the GSTP1 protein. Together, these findings show PKA- and PKC-dependent phosphorylation as a significant post-translational mechanism of regulation of GSTP1 function. Together, these results further support S42 and S184 as major phosphor-acceptor residues for PKA and PKC and suggest that the increased activity of the phospho-GSTP1 was not simply a consequence of the negative charge introduced in the GSTP1 protein by the phosphate group.All eight PKC isoforms, PKC-α, PKC-βI, PKC-βII, PKC-ε, PKC-γ, PKC-η, and PKC-ζ phosphorylated the GSTP1 protein efficiently	SIGNOR-276021
Q53ET0	P54646	0	phosphorylation	down-regulates	0.489	Phosphorylation on the ser171 residue of crtc2 by ampk and ampk-related kinases, including the salt-inducible kinases (siks), is critical for determining the activity, cellular localization, and degradation of crtc2	SIGNOR-142211
P12931	P08559	1	phosphorylation	down-regulates activity	0.348	Src inactivated PDH through direct phosphorylation of tyrosine-289 of PDH E1α subunit (PDHA1).	SIGNOR-277204
O15105	P36897	2	binding	down-regulates activity	0.789	SMAD7 functions as an antagonist to TGFB by binding to the TBRI and thus inhibiting activation of SMAD2 and SMAD3.	SIGNOR-64088
P46531	P35222	2	binding	up-regulates	0.775	Beta-catenin can regulate the level and transcriptional activity of the notch1 and notch1 intracellular domain (nicd). The in vivo and in vitro results demonstrate that beta-catenin binds with notch1 and nicd, for which its armadillo repeat domain is essential.	SIGNOR-236858
P21802	O60258	2	binding	up-regulates	0.687	Fgfs bind and activate high-affinity receptor tyrosine kinases. The cloning of fgf receptors (fgfrs) has identified four distinct genes	SIGNOR-42365
Q13188	P35240	2	binding	up-regulates activity	0.327	NF2 is activated by oxidative stress in cardiomyocytes and mouse myocardium and facilitates apoptosis. NF2 promotes I/R injury through activation of Mst1 and inhibition of Yap, thereby regulating Hippo signaling in the adult heart.	SIGNOR-261955
P49841	P35659	1	phosphorylation	down-regulates quantity by destabilization	0.437	These data suggest that the E3 ligase SCFFbxw7-α degrades p-DEK in a GSK-3β–dependent manner.Therefore, the phosphorylation of DEK by GSK-3β is a crucial step to mediate Tpm RNA splicing.	SIGNOR-276303
P24385	P01241	0	transcriptional regulation	up-regulates quantity by expression	0.2	Autocrine hGH increased the transcription and subsequent mRNA level and protein expression of c-Myc, Cyclin D1, and Bcl-2 in human mammary epithelial cells	SIGNOR-261629
Q12756	Q9HCD6	2	binding	up-regulates activity	0.248	Kinesin-3 Family Member KIF1A Interacts with Liprin-α and TANC2. TANC2 and Liprin-α Recruit KIF1A-Driven DCVs in Dendritic Spines. Upon Ca2+/CaM binding, KIF1A is activated, allowing for DCV loading and motility. KIF1A-driven DCVs are recruited in dendritic spines by liprin-α and TANC2, which ensure a precise mechanism of synaptic tagging for the vesicles.	SIGNOR-266891

P00533

Q32MZ4

0

transcriptional regulation

down-regulates quantity by repression

0.293

GC-binding factor 2 (GCF2) is a transcriptional repressor that decreases activity of the epidermal growth factor receptor (EGFR) and other genes. |Deletion mutants of GCF2 revealed that amino acids 429–528 are required for both DNA binding and repression of the EGFR promoter.

SIGNOR-266057

Q13535

Q99708

1

phosphorylation

up-regulates

0.615

Characterization of this site using phospho-specific antibodies and mutational analysis reveals that it is phosphorylated by atr and is required for binding of ctip to chromatin and subsequent processive resection.

SIGNOR-200245

Q15818

Q07812

1

relocalization

up-regulates activity

0.2

Immunofluorescence staining and subcellular fractionation analyses revealed increased mitochondrial translocation of Bad and Bax proteins from cytoplasm following OGD (4 h) and simultaneously increased release of Cyt C from mitochondria followed by activation of caspase-3. NP1 protein was immunoprecipitated with Bad and Bax proteins; OGD caused increased interactions of NP1 with Bad and Bax, thereby, facilitating their mitochondrial translocation and dissipation of mitochondrial membrane potential

SIGNOR-261439

Q08117

Q96QT6

2

binding

up-regulates activity

0.2

We have cloned and characterized a new member of the PHD zinc finger family called Pf1 that interacts with two global transcription corepressors: mSin3A and TLE. Pf1 interacts with TLE. The Groucho/TLE proteins are members of an abundant corepressor family, and we hypothesized that Pf1 might interact with TLE family members. Together, these data suggest that in the absence of interactions with mSin3A, Gal4-Pf1 (102–273 L212P/A216P)-dependent repression can be attributed to interaction with endogenous TLE.

SIGNOR-266990

P15172

Q8IXJ6

0

deacetylation

down-regulates

0.376

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

SIGNOR-104251

P01106

P49840

0

phosphorylation

down-regulates quantity by destabilization

0.406

Similar to c-myc, similar to c-myc, we report here that phosphorylation of c-jun by gsk3 creates a high-affinity binding site for the e3 ligase fbw7, which targets c-jun for polyubiquitination and proteasomal degradation.

SIGNOR-138596

P17612

O14965

1

phosphorylation

up-regulates activity

0.512

Aurora2 is regulated by phosphorylation. phosphorylation occurs on a conserved residue, Threonine 288, within the activation loop of the catalytic domain of the kinase and results in a significant increase in the enzymatic activity. Threonine 288 resides within a consensus motif for the cAMP dependent kinase and can be phosphorylated by PKA in vitro.

SIGNOR-250337

P15151

Q15762

2

binding

up-regulates activity

0.82

We focused on receptor-ligand interactions between CAFs and NK cell and found that cell-surface poliovirus receptor (PVR/CD155), a ligand of activating NK receptor DNAM-1, was downregulated in the CAFs compared with NEFs. |Poliovirus receptor (PVR/CD155) is a ligand of the paired NK receptors, DNAM-1 (activating) and TIGIT (inhibiting). NK cells can kill cancer cells expressing PVR via the DNAM-1-mediated activating signaling (11,12).

SIGNOR-261424

O43236

O60260

0

ubiquitination

down-regulates quantity by destabilization

0.2

Thus, Parkin degrades ARTS in a proteasome dependent manner.|Together, these results suggest that Parkin specifically ubiquitinates and degrades ARTS, and that this degradation may be linked to the pro-apoptotic function of ARTS.

SIGNOR-278642

O14921

P17612

0

phosphorylation

up-regulates quantity by stabilization

0.334

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

SIGNOR-259835

Q08050

O14757

0

phosphorylation

up-regulates activity

0.371

In addition, upon treatment with genotoxic agents, the checkpoint kinases Chk1 and Chk2 also phosphorylate and activate FOXM1.

SIGNOR-280224

Q15172

P36897

2

binding

up-regulates

0.261

In this report, we show that another wd-40 repeat protein, the balpha subunit of protein phosphatase 2a, associates with the cytoplasmic domain of type i tgf-beta receptors..[..] Furthermore, balpha enhances the growth inhibition activity of tgf-beta in a receptor-dependent manner

SIGNOR-60743

Q08881

P19174

1

phosphorylation

up-regulates

0.637

In t cells, the predominant tec kinase is itk, which functions downstream of the t-cell receptor to regulate phospholipase c-gamma.

SIGNOR-165803

P54762

Q969H4

2

binding

up-regulates activity

0.293

The phosphorylated CNK1 interacts with ephrinB1. The binding of ephrinB1 to CNK1 connects RhoA and p115RhoGEF with ephrinB1-associated MKK4, promoting JNK activation and cell migration.

SIGNOR-275921

Q9UHN6

Q86YJ5

0

ubiquitination

down-regulates quantity by destabilization

0.2

MARCH9, a member of the RING-CH family of transmembrane E3 ubiquitin ligases, down-regulates CD4, major histocompatibility complex-I (MHC), and ICAM-1 in lymphoid cells. To identify novel MARCH9 substrates, we used high throughput flow cytometry and quantitative mass spectrometry by stable isotope labeling by amino acids in cell culture (SILAC) to determine the differential expression of plasma membrane proteins in a MARCH9-expressing B cell line. This combined approach identified 13 potential new MARCH9 targets.

SIGNOR-271533

P12931

P50402

1

phosphorylation

down-regulates

0.451

Src phosphorylated emerin specifically at y59, y74 and y95; interestingly y-to-f substitutions at identified src sites reduced recombinant emerin binding to endogenous baf

SIGNOR-188308

P12931

Q9Y4K3

1

phosphorylation

up-regulates activity

0.565

To gain further insights into the molecular mechanisms, we employed mass spectrometry to identify the specific tyrosine residues of Traf6 that are phosphorylated by c-Src.By mutating these phosphorylation sites to phenylalanine, we disrupted Traf6-mediated polyubiquitination and subsequently observed the inactivation of AEP. This finding suggests that the phosphorylation of Traf6 by c-Src is crucial for AEP activation.

SIGNOR-277866

P38936

Q15831

0

phosphorylation

down-regulates activity

0.488

Mass spectrometry analysis of the phosphorylated CDKN1A identified Thr80 as the residue phosphorylated by LKB1 in vitro (Figure 4A and S5A).|UVB induced phosphorylation of LKB1 T366 mediates CDKN1A degradation.

SIGNOR-278253

Q92633

P50148

2

binding

up-regulates activity

0.544

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-257091

P04792

Q13237

0

phosphorylation

down-regulates

0.2

Purified pkg isoforms ia, ib, and ii all caused incorporation of phosphate in recombinant hsp27 at ser-78, ser-82, and thr-143, but not ser-15.These Studies indicate that hsp27 is a genuine substrate for pkg and that pkg may mediate inhibition of platelet aggregation through phosphorylation of hsp27 and subsequent prevent of actin polymerization

SIGNOR-186947

Q9NQW6

Q9UM11

2

binding

down-regulates quantity by destabilization

0.265

Ubiquitination of anillin required a destruction-box and was mediated by Cdh1, an activator of APC/C. Overexpression of Cdh1 reduced the levels of anillin, whereas inactivation of APC/C(Cdh1) increased the half-life of anillin.

SIGNOR-272654

Q9UKX2

P14859

0

transcriptional regulation

up-regulates quantity by expression

0.2

Myocyte enhancer factor-2 and serum response factor binding elements regulate fast Myosin heavy chain transcription in vivo. We show that the upstream promoter region of the gene most abundantly expressed in mouse skeletal muscles, IIb MyHC, retains binding activity and transcriptional activation for three positive transcription factors, the serum response factor, Oct-1, and myocyte enhancer factor-2, whereas the other two genes (IIa and IId/x) have nucleotide substitutions in these sites that reduce binding and transcriptional activation

SIGNOR-238757

P50148

P30968

2

binding

up-regulates activity

0.474

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

SIGNOR-257265

Q14344

Q9UBY5

2

binding

up-regulates

0.4

Serum-borne lysophosphatidic acid (lpa) and sphingosine 1-phosphophate (s1p) act through g12/13-coupled receptors to inhibit the hippo pathway kinases lats1/2 thereby activating yap and taz transcription co-activators, which are oncoproteins repressed by lats1/2.

SIGNOR-198547

P52630

P29597

0

phosphorylation

up-regulates activity

0.789

JAK1 and TYK2 will phosphorylate and activate STAT1 and STAT2 respectively, leading to the formation of the ternary interferon-stimulated gene factor 3 (ISGF3) complex, composed of STAT1, STAT2 and interferon regulatory factor 9 (IRF9).

SIGNOR-279133

P22681

P27986

1

ubiquitination

down-regulates

0.694

Cbl-b, a ring-type e3 ubiquitin protein ligase, is implicated in setting the threshold of t lymphocyte activation. The p85 regulatory subunit of phosphatidylinositol 3 kinase (pi3k) was identified as a substrate for cbl-b. We have shown that cbl-b negatively regulated p85 in a proteolysis-independent manner.

SIGNOR-110060

P01266

P07202

0

catalytic activity

up-regulates activity

0.505

After transport through the apical membrane, I− is covalently bound to the tyrosyl residues of Tg by thyroid peroxidase (TPO).

SIGNOR-259914

Q8IW41

Q15382

1

phosphorylation

down-regulates activity

0.401

Phosphorylation of Rheb at Ser 130 by PRAK impairs the nucleotide-binding ability of Rheb and inhibits Rheb-mediated mTORC1 activation.

SIGNOR-276313

Q8N0Z6

Q09472

2

binding

up-regulates activity

0.563

DNA damage activates ATM kinase which then phosphorylates Strap at Ser 203 (red circles). Phosphorylated Strap is stabilized and undergoes nuclear accumulation where it assembles into a co-activator complex, which includes p300 and cofactors such as JMY

SIGNOR-262646

P98177

P24941

0

phosphorylation

down-regulates

0.518

Additionally, ck1, dyrk1a, and cdk2 also phosphorylate foxos at various sites to inhibit foxos activity

SIGNOR-183655

P40189

Q16619

2

binding

up-regulates

0.627

In the cos-7 cell line demonstrate that gp130-gp190 heterocomplex formation is essential for ct-1 signaling

SIGNOR-46509

Q16620

Q92529

2

binding

up-regulates

0.755

Our present study established that n-shc and sck are expressed in a region-specific manner in the brain and that n-shc is a higher affinity adapter molecule than sck for trka and trkb receptors

SIGNOR-55864

O95714

Q96JN8

1

polyubiquitination

down-regulates quantity by destabilization

0.456

NEURL4 is a substrate of HERC2, and together these results indicate that the NEURL4-HERC2 complex participates in the ubiquitin-dependent regulation of centrosome architecture.

SIGNOR-272921

Q9BUB5

P06730

1

phosphorylation

up-regulates

0.779

Mnk1 and mnk2 regulate protein synthesis by phosphorylating the initiation factor eif4e.

SIGNOR-166646

P29350

P06239

2

dephosphorylation

down-regulates activity

0.613

We demonstrate that shp-1 dephosphorylates the lymphoid-specific src family kinase lck at tyr-394. Because phosphorylation of tyr-394 activates lck, the fact that shp-1 specifically dephosphorylates this site suggests that shp-1 is a negative regulator of lck.

SIGNOR-106604

Q9BXK1

P12931

0

phosphorylation

up-regulates activity

0.245

We further confirmed that the Tyr-10 residue of KLF16 is phosphorylated in uterine cells (Fig. 7c). Additional experiments using both pharmacological and dominant negative inhibitors of Src further supported a role for this tyrosine kinase in modulating the activity of KLF16 (Fig. 7, d and f).

SIGNOR-276398

P49841

P08581

0

phosphorylation

up-regulates activity

0.308

MET phosphorylated and activated GSK3B at tyrosine 56, which decreased the expression of PDL1 by liver cancer cells.

SIGNOR-277428

Q9BQE3

Q14980

2

binding

up-regulates

0.258

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

SIGNOR-116677

O15519

P05771

0

phosphorylation

up-regulates quantity by stabilization

0.2

Here, we identify serine 193 as a novel in vivo phosphorylation site of all c-FLIP proteins. c-FLIP S193 phosphorylation is mediated by PKCa and PKCb.S193 phosphorylation increases the stability of the short c-FLIP proteins

SIGNOR-276146

P19105

P53355

0

phosphorylation

up-regulates activity

0.275

DAPK Phosphorylates Myosin II RLC in Vitro and in Vivo. Together these results show that similar to the conventional MLCKs, Ser-19 is the primary RLC residue phosphorylated by DAPK and that phosphorylation of Thr-18 is also possible.

SIGNOR-262842

P49841

P10275

1

phosphorylation

down-regulates activity

0.649

Glycogen synthase kinase-3 beta is involved in the phosphorylation and suppression of androgen receptor activity.|In particular, we showed that glycogen synthase kinase-3 beta phosphorylates the androgen receptor, thereby inhibiting androgen receptor-driven transcription.

SIGNOR-279334

O15169

P36873

0

dephosphorylation

down-regulates activity

0.269

The data suggest that PP1 controls Wnt signaling through interaction with, and regulated dephosphorylation of, axin| Axin phosphorylation markedly enhances the binding of glycogen synthase kinase 3, leading to a more active beta-catenin destruction complex. Wnt-regulated changes in axin phosphorylation, mediated by PP1, may therefore determine beta-catenin transcriptional activity| Four sites, S80, S82, S222, and S473, were identified to be PP1 regulated

SIGNOR-248494

P50750

P50613

0

phosphorylation

up-regulates activity

0.551

Cdk7 activates Cdk9 in vitro .|Cdk7 phosphorylates wild-type Cdk9 on Thr186, resulting in increased activity towards a recombinant GST-Spt5 substrate.

SIGNOR-279455

Q13362

P27361

2

binding

down-regulates

0.42

B56-containing pp2a dephosphorylate erk and their activity is controlled by the early gene iex-1 and erk

SIGNOR-144328

P27986

P06239

0

phosphorylation

down-regulates activity

0.623

the regulatory p85 subunit of phosphatidylinositol 3-kinase is phosphorylated on tyrosine residues. We report that this phosphorylation event is readily catalyzed by the Abl and Lck protein-tyrosine kinases in vitro, by Bcr-Abl or a catalytically activated Lck-Y505F in co-transfected COS cells. we have mapped a major phosphorylation site to Tyr-688 in the C-terminal SH2 domain of p85. Tyrosine phosphorylation of p85 in vitro or in vivo was not associated with detectable change in the enzymatic activity of the phosphatidylinositol 3-kinase heterodimer, but correlated with a strong reduction in the binding of some, but not all, phosphoproteins to the SH2 domains of p85.

SIGNOR-251383

P63096

P30411

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-256695

P04792

Q13976

0

phosphorylation

down-regulates

0.274

Purified pkg isoforms ia, ib, and ii all caused incorporation of phosphate in recombinant hsp27 at ser-78, ser-82, and thr-143, but not ser-15.These Studies indicate that hsp27 is a genuine substrate for pkg and that pkg may mediate inhibition of platelet aggregation through phosphorylation of hsp27 and subsequent prevent of actin polymerization

SIGNOR-186784

P05412

P68400

0

phosphorylation

down-regulates

0.592

Casein kinase ii is a negative regulator of c-jun dna binding and ap-1 activitywe show that two of these sites, thr-231 and ser-249, are phosphorylated by casein kinase ii (ckii).

SIGNOR-19607

P42336

P63211

2

binding

up-regulates

0.432

Gbetagamma subunits released from gi can activate pi3k (phosphoinositide 3-kinase), and can be therefore implicated in smo-dependent activation of akt

SIGNOR-154261

Q9NQ66

O95837

2

binding

up-regulates activity

0.468

This suggests that both Gal4 and Gal6 can activate PLC b1.

SIGNOR-278119

P28482

P49137

1

phosphorylation

up-regulates

0.507

Using novel methodology we demonstrate that activation of mapkap kinase-2 requires the phosphorylation of any two of the three residues thr222, ser272 and thr334. gst-mapkap kinase-2 lacking the n-terminal domain was inactive, but activated fully when phosphorylated at thr222, ser272 and thr334 by p42 mapk or rk.

SIGNOR-44343

O15354

O60260

0

ubiquitination

down-regulates quantity by destabilization

0.2

Parkin is a protein of 465 amino acids, and its structure includes a ubiquitin homologous domain in its N terminus and two RING finger domains in its C terminus. Molecular studies have determined that parkin is an E3 ubiquitin ligase function, implicating parkin in the ubiquitin-proteasome system, and raising the possibility that mutations in the gene lead to loss or diminished function. Three substrates for the ubiquitin-ligase function of parkin have been identified to date.1. A 22kDa glycosolated form of alpha-synuclei|2. Parkin-associated endothelin receptor-like receptor (Pael-R).

SIGNOR-249706

O00192

Q96RT1

2

binding

up-regulates activity

0.2

We characterized the interactions between the Erbin PDZ domain and both ARVCF and δ-catenin in vitro and in vivo. endogenous δ-catenin and Erbin co-localized in and co-immunoprecipitated from neurons. These results suggest that δ-catenin and ARVCF may function to mediate the association of Erbin with the junctional cadherin-catenin complex.

SIGNOR-252119

P23396

P28482

0

phosphorylation

up-regulates

0.2

Erk phosphorylates threonine 42 residue of ribosomal protein s3.

SIGNOR-137955

Q05397

Q14680

0

phosphorylation

up-regulates activity

0.2

As the aforementioned results showed that MELK promotes FAK phosphorylation, and it is well known that FAK is an important regulator of cell migration and invasion, we speculated that MELK could regulate cell migration and invasion via the FAK/Paxillin pathway.|Finally, knockdown of MELK decreased the phosphorylation of the FAK and paxillin, and prevented gastrin stimulated FAK and paxillin phosphorylation.

SIGNOR-279230

O14874

P12694

1

phosphorylation

down-regulates

0.609

Phosphorylation sites and inactivation of branched-chain alpha-ketoacid dehydrogenase isolated from rat heart, bovine kidney, and rabbit liver, kidney, heart, brain, and skeletal muscle.

SIGNOR-25084

O43318

Q15797

1

phosphorylation

up-regulates activity

0.373

This analysis showed that phosphorylation of Smad1 at the C-terminal serines S463 and S465 was increased by co-expression of constitutively active TAK1.

SIGNOR-279419

O75581

P56704

2

binding

up-regulates activity

0.79

Here, we present evidence that lrp6 is internalized with caveolin and that the components of this endocytic pathway are required not only for wnt-3a-induced internalization of lrp6 but also for accumulation of beta-catenin.

SIGNOR-148671

P41279

P45985

1

phosphorylation

up-regulates

0.559

Furthermore, we found that immunoprecipitated tpl-2 could directly phosphorylate and activate both mek-1 and mkk4 (also known as sek-1)

SIGNOR-196744

P27987

P17612

0

phosphorylation

down-regulates activity

0.351

Two isoforms of the inositol 1,4,5-trisphosphate 3-kinase have been identified, the A form and the B form. phosphorylation of isoform A by the cyclic AMP-dependent protein kinase increased activity 1.5-fold, whereas phosphorylation of isoform B decreased activity by 45%. major phosphorylation sites in the protein are Ser119 for PKA. Ser119 in the A isoform is conserved in the B isoform as Ser328

SIGNOR-249995

P61296

2

binding

up-regulates activity

0.2

The basic helix-loop-helix factor, HAND2, functions as a transcriptional activator by binding to E-boxes as a heterodimer

SIGNOR-223476

P26010

Q9Y490

2

binding

up-regulates activity

0.585

Over the past 10 years, the binding of talin to the cytoplasmic tail of integrin-β subunits has been established to have a key role in integrin activation. Binding of the phosphotyrosinebinding (PTB)-domain-like subdomain of the protein 4.1, ezrin, radixin, moesin (FERM) domain of talin to the conserved WxxxNP(I/L)Y motif of the β-integrin tail permits additional weaker interactions between talin and the membrane-proximal region of the tail that trigger integrin activation, probably through the disruption of inhibitory interactions between α- and β-subunit cytoplasmic tails.

SIGNOR-257633

P02679

P02751

2

binding

down-regulates activity

0.553

Fibrinogen y-chain carboxyterminal (GQQHHLGGAKQAGDV) peptides inhibit fibrinogen, fibronectin (Fn), vitronectin, and von Willebrand factor (vWF) binding to the platelet glycoprotein Ilb-Illa complex (GP lIbII1a).

SIGNOR-251970

Q13535

Q9BXW9

1

phosphorylation

up-regulates

0.673

In the present study, we identify two novel dna damage-inducible phosphorylation sites on fancd2, threonine 691 and serine 717. Atr phosphorylates fancd2 on these two sites, thereby promoting fancd2 monoubiquitination and enhancing cellular resistance to dna cross-linking agents

SIGNOR-149305

P52732

Q8TDX7

0

phosphorylation

up-regulates activity

0.407

NEK7 regulates these processes in part through phosphorylation of the kinesin Eg5/KIF11, promoting its accumulation on microtubules in distal dendrites.

SIGNOR-273890

Q9H0R8

Q13501

2

binding

up-regulates activity

0.79

P62 binds both to lc3a and -b and the related gabarap family proteins/this interaction is necessary for autophagic degradation of p62-positive cytoplasmic inclusion bodies containing ubiquitinated proteins. We also demonstrate that alis are indistinguisha

SIGNOR-156304

Q13501

P60520

2

binding

up-regulates activity

0.862

P62 binds both to lc3a and -b and the related gabarap family proteins/this interaction is necessary for autophagic degradation of p62-positive cytoplasmic inclusion bodies containing ubiquitinated proteins. We also demonstrate that alis are indistinguisha

SIGNOR-156307

P17676

P41440

1

transcriptional regulation

up-regulates quantity by expression

0.2

Collectively, these results identify transcriptionally important regions in the hRFC-C minimal promoter that include a GC-box and CCAAT-box, and suggest that cooperative interactions between Sp1 and C/EBP beta are essential for hRFC-C transactivation.

SIGNOR-254053

O75030

P63279

0

ubiquitination

down-regulates

0.565

Furthermore, we identified lysine 201 as a potential ubiquitination site. A lysine to arginine mutation abolished mitf (k201r) degradation by hubc9 in vivo.

SIGNOR-75117

P38398

Q15424

1

ubiquitination

up-regulates quantity by stabilization

0.2

These results suggest that the BRCA1 and BARD1 heterodimer ubiquitinates SAFB and increases SAFB protein levels.

SIGNOR-278624

Q92576

P24928

2

binding

down-regulates activity

0.46

PHF3 interacts with RNA polymerase II through the SPOC domain. PHF3 negatively regulates mRNA levels. Here, we identify PHD-finger protein 3 (PHF3) as a regulator of transcription and mRNA stability that docks onto Pol II CTD through its SPOC domain. Our data suggest that PHF3 acts as a prominent effector of neuronal gene regulation by bridging transcription with mRNA decay. PHF3 SPOC preferentially binds RNA Pol II CTD phosphorylated on Serine-2

SIGNOR-266965

Q13315

Q8N163

1

phosphorylation

up-regulates activity

0.587

Here, we report that, in human cell lines, DNA damage triggered the phosphorylation of DBC1 on Thr454 by ATM (ataxia telangiectasia-mutated) and ATR (ataxia telangiectasia and Rad3-related) kinases. Phosphorylated DBC1 bound to and inhibited SIRT1, resulting in the dissociation of the SIRT1-p53 complex and stimulating p53 acetylation and p53-dependent cell death.

SIGNOR-267661

Q99873

P48729

0

phosphorylation

up-regulates activity

0.2

CSNK1a1 directly bound and phosphorylated PRMT1 to control its genomic targeting to PRMT1-sustained proliferation genes as well as PRMT1-suppressed differentiation genes.|Taken together, these data support a provisional model in which CSNK1a1 directs PRMT1 to genomic targets that promote self-renewal and suppress terminal differentiation.In the context of transcription regulation, PRMT1 has been generally considered as a transcriptional co-activator.

SIGNOR-279733

P12931

Q07954

1

phosphorylation

up-regulates activity

0.394

We recently observed that the ldl receptor-related protein 1 (lrp-1) is tyrosine phosphorylated in v-src-transformed cells.Of the four tyrosine residues present in the cytoplasmic domain of lrp-1, only tyr 63 is phosphorylated by v-src in vivo or in vitro. Using fibroblasts deficient in src, yes and fyn, we were able to show that there are multiple kinases present in the cell that can phosphorylate lrp-1. Tyrosine-phosphorylated lrp-1 associates with shc, a ptb and sh2 domain containing signaling protein that is involved in the activation of ras

SIGNOR-101535

P21802

P62993

1

phosphorylation

up-regulates

0.773

Inhibition of basal fgf receptor signaling by dimeric grb2.

SIGNOR-197980

P25963

O14965

0

phosphorylation

down-regulates activity

0.541

The results of the in vitro kinase assay, using purified human recombinant AURKA and IkappaBalpha proteins, confirmed that AURKA can directly phosphorylate IkappaBalpha (Ser32) at a concentration as low as 2.5 ng/mul (XREF_FIG).|While an earlier study suggested that AURKA down-regulates IkappaBalpha indirectly through activation of the PI3K and AKT pathway 35, our data demonstrate, for the first time, that AURKA directly binds and phosphorylates the IkappaBalpha subunit, leading to activation of NF-kappaB.

SIGNOR-278912

P34972

P63096

2

binding

up-regulates activity

0.468

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-256700

P55085

P07477

0

cleavage

up-regulates activity

0.388

Mass spectrometry studies of PAR2E predicted activation of PAR2 by trypsin through cleavage at the Arg36-Ser37 site, no effect of thrombin, and inactivation of the receptor by plasmin, calpain and leukocyte elastase, cathepsin G, and proteinase 3.

SIGNOR-263602

Q9NPG1

P61586

2

binding

up-regulates activity

0.344

Upon ligand binding, non-canonical wnt signaling controls tissue polarity and cell movement through the activation of rhoa, c-jun n-terminal kinase (jnk), and nemo-like kinase (nlk) signaling cascades.

SIGNOR-167865

P51692

Q13882

0

phosphorylation

up-regulates

0.429

Phosphospecific antibodies, mutational analysis, and in vitro kinase assays demonstrated that brk specifically mediated stat5b phosphorylation at the activating tyrosine, y699.

SIGNOR-159066

P09471

Q9H1C0

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-256997

O60674

P15260

2

phosphorylation

up-regulates activity

0.714

In the classical model of IFNgamma signaling, dimeric IFNgamma cross-links the IFNGR1 receptor subunit that results in allosteric changes in receptor cytoplasmic domain. This results in movement of JAK2 from receptor subunit IFNGR2 to IFNGR1. The JAKs autophosphorylate and then phosphorylate IFNGR1 cytoplasmic domain. This results in binding, phosphorylation, and dimer formation of STAT1_. The dimeric STAT1_ dissociates from receptor and undergoes nuclear translocation via an intrinsic NLS for specific gene activation

SIGNOR-249490

P42684

P04040

1

phosphorylation

up-regulates activity

0.34

C-abl and arg phosphorylated catalase at tyr231 and tyr386 in vitrocatalase is a major effector in the defense of aerobic cells against oxidative stress. Recent studies have shown that catalase activity is stimulated by the c-abl and arg tyrosine kinases

SIGNOR-101306

Q8N6T3

Q5S007

2

binding

up-regulates

0.579

The gtp hydrolysis activity of lrrk2 is markedly enhanced by arfgap1 supporting a role for arfgap1 as a gtpase-activating protein for lrrk2.Lrrk2 and arfgap1 interact in vitro in mammalian cells and in vivo in brain, and co-localize in the cytoplasm and at golgi membranes

SIGNOR-196264

P09467

P17010

0

transcriptional regulation

down-regulates quantity by repression

0.2

For instance, nucleophosmin (NPM1) and zinc-finger protein X-linked (ZFX) bind to the E-box and ZFX binding site on the FBP1 promoter, respectively, and restrain FBP1 expression to facilitate aerobic glycolysis in PDAC and melanoma

SIGNOR-267595

Q9UHD0

Q6UXL0

2

binding

up-regulates

0.719

Il-19 signals only through the type i il-20r complex.

SIGNOR-151820

P09471

Q9GZQ4

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 ≥ -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-257010

Q16143

Q9NYY3

0

phosphorylation

down-regulates activity

0.248

Polo-like kinase (plk) family (plk1, plk2, and plk3) phosphorylate alpha-syn and beta-syn specifically at ser-129 and ser-118, respectively. Polo-like kinase 2 (plk2) phosphorylates alpha-synuclein at serine 129 in central nervous system. The membrane association of pd-linked mutant alpha -synuclein, but not wild-type -synuclein, was increased by serine 129 phosphorylation.

SIGNOR-189049

P0CG47

Q96BN8

0

cleavage

up-regulates quantity

0.671

Here we provide data suggesting that two of the four mammalian ubiquitin precursors, UBA52 and UBA80, are processed mostly post-translationally whereas the other two, UBB and UBC, probably undergo a combination of co- and post-translational processing. Using an unbiased biochemical approach we found that UCHL3, USP9X, USP7, USP5 and Otulin/Gumby/FAM105b are by far the most active DUBs acting on these precursors.

SIGNOR-270819

O14745

P43250

0

phosphorylation

down-regulates activity

0.405

GRK6A phosphorylates NHERF on Ser289, the primary site of constitutive phosphorylation of NHERF in HEK-293 cells. The interaction of NHERF and NHE3 is mediated by the region of NHERF encompassing the second PDZ domain and the tail (25), and it is therefore reasonable that phosphorylation of the serine-rich stretch in the center of this region (including Ser289) might affect the physical interaction of NHERF with NHE3.

SIGNOR-251214

P09211

Q02156

0

phosphorylation

up-regulates activity

0.2

Peptide phosphorylation analyses and both phosphorylation and enzyme kinetic studies with GSTP1 proteins mutated at candidate amino acid residues established Ser-42 and Ser-184 as putative phospho-acceptor residues for both kinases in the GSTP1 protein. Together, these findings show PKA- and PKC-dependent phosphorylation as a significant post-translational mechanism of regulation of GSTP1 function. Together, these results further support S42 and S184 as major phosphor-acceptor residues for PKA and PKC and suggest that the increased activity of the phospho-GSTP1 was not simply a consequence of the negative charge introduced in the GSTP1 protein by the phosphate group.All eight PKC isoforms, PKC-α, PKC-βI, PKC-βII, PKC-ε, PKC-γ, PKC-η, and PKC-ζ phosphorylated the GSTP1 protein efficiently

SIGNOR-276021

Q53ET0

P54646

0

phosphorylation

down-regulates

0.489

Phosphorylation on the ser171 residue of crtc2 by ampk and ampk-related kinases, including the salt-inducible kinases (siks), is critical for determining the activity, cellular localization, and degradation of crtc2

SIGNOR-142211

P12931

P08559

1

phosphorylation

down-regulates activity

0.348

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

SIGNOR-277204

O15105

P36897

2

binding

down-regulates activity

0.789

SMAD7 functions as an antagonist to TGFB by binding to the TBRI and thus inhibiting activation of SMAD2 and SMAD3.

SIGNOR-64088

P46531

P35222

2

binding

up-regulates

0.775

Beta-catenin can regulate the level and transcriptional activity of the notch1 and notch1 intracellular domain (nicd). The in vivo and in vitro results demonstrate that beta-catenin binds with notch1 and nicd, for which its armadillo repeat domain is essential.

SIGNOR-236858

P21802

O60258

2

binding

up-regulates

0.687

Fgfs bind and activate high-affinity receptor tyrosine kinases. The cloning of fgf receptors (fgfrs) has identified four distinct genes

SIGNOR-42365

Q13188

P35240

2

binding

up-regulates activity

0.327

NF2 is activated by oxidative stress in cardiomyocytes and mouse myocardium and facilitates apoptosis. NF2 promotes I/R injury through activation of Mst1 and inhibition of Yap, thereby regulating Hippo signaling in the adult heart.

SIGNOR-261955

P49841

P35659

1

phosphorylation

down-regulates quantity by destabilization

0.437

These data suggest that the E3 ligase SCFFbxw7-α degrades p-DEK in a GSK-3β–dependent manner.Therefore, the phosphorylation of DEK by GSK-3β is a crucial step to mediate Tpm RNA splicing.

SIGNOR-276303

P24385

P01241

0

transcriptional regulation

up-regulates quantity by expression

0.2

Autocrine hGH increased the transcription and subsequent mRNA level and protein expression of c-Myc, Cyclin D1, and Bcl-2 in human mammary epithelial cells

SIGNOR-261629

Q12756

Q9HCD6

2

binding

up-regulates activity

0.248

Kinesin-3 Family Member KIF1A Interacts with Liprin-α and TANC2. TANC2 and Liprin-α Recruit KIF1A-Driven DCVs in Dendritic Spines. Upon Ca2+/CaM binding, KIF1A is activated, allowing for DCV loading and motility. KIF1A-driven DCVs are recruited in dendritic spines by liprin-α and TANC2, which ensure a precise mechanism of synaptic tagging for the vesicles.

SIGNOR-266891