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
Q13546	P23458	0	phosphorylation	up-regulates activity	0.2	In addition , our results suggest JAK1 could be recruited to TNF-RSC to modulate RIPK1 activity .\|In this study, we show that non-receptor tyrosine kinases JAK1 and SRC could phosphorylate RIPK1 on tyrosine 384 (Y384) in human RIPK1 (Y383 in mouse RIPK1), and serve as essential regulators of RIPK1 in the TNFR1 signaling pathway.	SIGNOR-278948
P50461	P15172	2	binding	up-regulates activity	0.468	we found that nuclear MLP functions through a physical interaction with the muscle basic helix-loop-helix (bHLH) transcription factors MyoD, MRF4, and myogenin. we propose that it serves as a cofactor for the myogenic bHLH proteins by increasing their interaction with specific DNA regulatory elements.	SIGNOR-241116
P12755	Q6ZNA4	0	ubiquitination	down-regulates	0.595	On tgf-beta treatment, the e3 ubiquitin ligase arkadia mediates degradation of ski in a smad-dependent manner	SIGNOR-178598
P31749	Q6ZVD8	0	dephosphorylation	down-regulates	0.773	Here, we identify a protein phosphatase, ph domain leucine-rich repeat protein phosphatase (phlpp), that specifically dephosphorylates the hydrophobic motif of akt (ser473 in akt1), triggering apoptosis and suppressing tumor growth.[...] These data are consistent with phlpp terminating akt signaling by directly dephosphorylating and inactivating akt.	SIGNOR-252602
Q9UBE8	P10242	1	phosphorylation	down-regulates activity	0.714	Furthermore, the downregulation of c-Myb by NLK overexpression could be inhibited in cells that had been treated with the 26S proteasome inhibitor MG132 but not in those treated with DMSO ( ).\|HIPK2 and NLK directly bind to c-Myb, and NLK phosphorylates c-Myb at multiple sites, resulting in its ubiquitination and proteasome-dependent degradation [32].	SIGNOR-280049
Q8WV16	Q9NRC1	2	binding	down-regulates quantity by destabilization	0.2	We found that both CUL4A and CUL4B can form an E3 complex with DNA damage-binding protein 1 (DDB1) and DDB1-CUL4-associated factor 4 (DCAF4). In vitro and in vivo ubiquitination analyses indicate that CRL4DCAF4 E3 ligase specifically directs degradation of ST7 (suppression of tumorigenicity 7).	SIGNOR-272303
P01903	P48382	0	transcriptional regulation	up-regulates quantity by expression	0.503	In this report, we correlate the loss of IFN-γ induction of MHC class II genes with the identification of a molecular defect in an essential regulator, namely RFX5. \| We have further confirmed this finding by showing that new RFX5 leucine mutants created in vitro are incapable of transactivating a class II promoter, suggesting the identification of residues essential for RFX activity.	SIGNOR-266228
O75496	Q9H211	2	binding	down-regulates activity	0.972	Here we show that geminin interacts tightly with Cdt1, a recently identified replication initiation factor necessary for MCM loading.	SIGNOR-261680
Q8WWN8	P63000	1	gtpase-activating protein	down-regulates activity	0.47	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-260456
P02511	P22914	2	binding	up-regulates activity	0.538	Human gamma-crystallins are long-lived, unusually stable proteins of the eye lens exhibiting duplicated, double Greek key domains. The lens also contains high concentrations of the small heat shock chaperone alpha-crystallin, which suppresses aggregation of model substrates in vitro. Mature-onset cataract is believed to represent an aggregated state of partially unfolded and covalently damaged crystallins. The alphaB-crystallin oligomers formed long-lived stable complexes with their gammaD-crystallin substrates. These in vitro results provide support for protein unfolding/protein aggregation models for cataract, with alpha-crystallin suppressing aggregation of damaged or unfolded proteins through early adulthood but becoming saturated with advancing age.	SIGNOR-253623
P23467	Q02763	1	dephosphorylation	down-regulates activity	0.555	Simultaneous inhibition of Tie2 cleavage and VE-PTP synergistically enhances Tie2 activation by up to 10-fold (Fig. 7A).\|Tie2 activation is also importantly regulated by vascular endothelial protein tyrosine phosphatase (VE-PTP), which dephosphorylates Tie2 to inhibit its vascular stabilizing effects .\|Tie2 activation is also importantly regulated by vascular endothelial protein tyrosine phosphatase (VE-PTP), which dephosphorylates Tie2 to inhibit its vascular stabilizing effects.	SIGNOR-277059
O75475	P42574	0	cleavage	down-regulates	0.348	Ledgf/ p75 has a cooh-terminally truncated splice variant, p52 / during apoptosis, caspase-3 cleaved p52 to generate a p38 fragment that lacked the nh2-terminal pwwp domain and failed to transactivate the hsp27 promoter in reporter assays. However, p38 retained chromatin association properties and repressed the transactivation potential of ledgf/p75	SIGNOR-180144
Q96GM5	Q96EP1	0	polyubiquitination	down-regulates quantity by destabilization	0.307	Here we report that CHFR interacts with BRG1, SNF5, and BAF60a of the SWI/SNF-like BAF complex and ubiquitinates them to target for degradation through a proteasome-mediated pathway, and that SRG3/mBAF155 stabilizes these components by blocking their interaction with CHFR. These results suggest that CHFR enhances the degradation of the components of the SWI/SNF-like BAF complex by inducing their poly-ubiquitination.	SIGNOR-271459
P01236	P31270	0	transcriptional regulation	up-regulates quantity by expression	0.351	HoxA-11 enhanced upregulation of PRL only in differentiated cells.	SIGNOR-261630
O95837	P25100	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-257191
P08754	P08908	2	binding	up-regulates activity	0.57	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-256836
P08253	Q13753	1	cleavage	up-regulates activity	0.471	Induction of Cell Migration by Matrix Metalloprotease-2 Cleavage of Laminin-5\|MMP2 cleaved the Ln-5 gamma2 subunit at residue 587, exposing a putative cryptic promigratory site on Ln-5 that triggers cell motility. This altered form of Ln-5 is found in tumors and in tissues undergoing remodeling, but not in quiescent tissues. Cleavage of Ln-5 by MMP2 and the resulting activation of the Ln-5 cryptic site may provide new targets for modulation of tumor cell invasion and tissue remodeling.	SIGNOR-253240
P29966	Q16512	0	phosphorylation	down-regulates activity	0.365	PRK1 phosphorylates MARCKS at the PKC sites: serine 152, serine 156 and serine 163.	SIGNOR-249671
P50406	P50148	2	binding	up-regulates activity	0.344	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-257340
Q92952	P00533	0	phosphorylation	up-regulates activity	0.2	These results demonstrate the novel information that hSKCa1 channels are inhibited by genistein, T25 and AG556 via EGFR tyrosine kinase inhibition, which is related to the phosphorylation of Tyr(109) in the N-terminus.	SIGNOR-276490
Q02750	P10398	0	phosphorylation	up-regulates	0.74	Our data demonstrated that a-raf is, indeed, a mek1 activator and may play a role in growth factor signaling\|The immunoprecipitates were assayed for GST-MEK1 activation. D, activation of MEK1 by A-Raf requires the presence of serine residue 218 and 222.	SIGNOR-235944
P27986	P03372	2	binding	up-regulates	0.628	Recently, it has been known that er activates phosphatidylinositol-3-oh kinase (pi3k) through binding with the p85 regulatory subunit of pi3k.	SIGNOR-140470
O14836	Q9Y275	2	binding	up-regulates	0.781	Tumor necrosis factor (tnf) receptor superfamily member taci is a high affinity receptor for tnf family members april and blys.	SIGNOR-81360
Q96PZ7	P0C0L5	2	binding	down-regulates quantity	0.2	CUB and sushi multiple domains 1 (CSMD1) is a relatively poorly studied large transmembrane protein of 390 kDa composed of 14 N-terminal CUB domains interspersed with complement control protein (CCP) domains followed by 15 consecutive CCP domains. The active domains of CSMD1 were then identified in CCP17-21, which were shown to interact with C4b and C3b and present these complement proteins for degradation by factor	SIGNOR-265149
Q99835	Q9UMX1	2	binding	down-regulates activity	0.64	In addition to activating g(i), smo signals through its c-terminal tail to inhibit suppressor of fused, resulting in stabilization and activation of the gli family of transcription factors, which execute a transcriptional response to so-called canonical hh signaling.	SIGNOR-177656
Q9UNE7	O14654	1	polyubiquitination	down-regulates quantity by destabilization	0.2	IRS4 was phosphorylated at Ser859 by CK1γ2 in vitro and in vivo, which promoted the polyubiquitination and degradation of IRS4 through the ubiquitin/lysosome pathway by the carboxyl terminus of Hsc70-interacting protein(CHIP).	SIGNOR-277616
Q13131	P17252	0	phosphorylation	down-regulates activity	0.2	Purified PKC and Akt both phosphorylated AMPKα1 Ser487 in vitro with similar efficiency. PKC activation was associated with reduced AMPK activity, as inhibition of PKC increased AMPK activity and phorbol esters inhibited AMPK, an effect lost in cells expressing mutant AMPKα1 Ser487Ala. Consistent with a pathophysiological role for this modification, AMPKα1 Ser487 phosphorylation was inversely correlated with insulin sensitivity in human muscle.	SIGNOR-276459
P09619	P00519	2	phosphorylation	up-regulates activity	0.527	Here, we show that PDGFR-beta-phosphorylation of Abl kinases has functional consequences as PDGFR-beta phosphorylates Abl kinases on Y245 and Y412, sites known to be required for activation of Abl kinases.	SIGNOR-278319
P12931	Q13322	1	phosphorylation	down-regulates	0.447	Grb10 tyrosine phosphorylation was stimulated by expression of constitutively active src or fyn in cells and by incubation with purified src or fyn in vitro. The insulin stimulated or src/fyn-mediated tyrosine phosphorylation in vivo was significantly reduced when grb10 tyrosine 67 was changed to glycine. This mutant form of grb10 bound with higher affinity to the ir in cells than that of the wild-type protein, suggesting that tyrosine phosphorylation of grb10 may normally negatively regulate its binding to the ir.	SIGNOR-78706
Q14653	P55286	0	transcriptional regulation	up-regulates quantity	0.2	CHD8 binds to histone H3 di- and trimethylated on lysine 4. It resides on the human U6 promoter as well as the mRNA IRF3 promoter in vivo and contributes to efficient transcription from both these promoters	SIGNOR-266898
P06213	Q13480	1	phosphorylation	up-regulates activity	0.502	HGab-1 was phosphorylated by IR at eight tyrosine residues (Y242, Y285, Y373, Y447, Y472, Y619, Y657, and Y689). t Gab-1 is the major binding partner of PI-3 kinase in 3T3L1 cells when stimulated with insulin	SIGNOR-251310
Q16827	P07948	1	dephosphorylation	down-regulates activity	0.325	Both Lyn and ZAP70 were dephosphorylated by wild-type PTPROt, but not by its catalytic site mutant.\|Lyn kinase and ZAP70 are substrates of PTPROt in B-cells: Lyn inactivation by PTPROt sensitizes leukemia cells to VEGF-R inhibitor pazopanib.	SIGNOR-277144
Q9P0U3	P31749	1	desumoylation	down-regulates quantity by destabilization	0.28	Although multiple sites on Akt could be SUMOylated, K276 was identified as a major SUMO acceptor site. K276R or E278A mutation reduced SUMOylation of Akt but had little effect on its ubiquitination. Strikingly, these mutations also completely abolished Akt kinase activity. In support of these results, we found that expression of PIAS1 and SUMO1 increased Akt activity, whereas expression of SENP1 reduced Akt1 activity.	SIGNOR-252736
O14757	P19838	1	phosphorylation	down-regulates	0.275	Taken together, the above findings suggest that chk1 phosphorylates p50 at s329 and further, that this phosphorylation blocks p50 dna binding.	SIGNOR-195208
Q9Y5I2	Q9UN70	2	binding	up-regulates activity	0.2	The clustered protocadherins comprise the largest subfamily of the cadherin superfamily and are predominantly expressed in the nervous system. Pcdh-alpha proteins interact with beta1-integrin to promote cell adhesion. They also form oligomers with Pcdh-gamma proteins at the same membrane sites.	SIGNOR-265696
P08754	Q15391	2	binding	up-regulates activity	0.403	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-256866
Q14643	P35398	0	transcriptional regulation	up-regulates quantity by expression	0.242	RORα regulates the expression of several genes in Purkinje cells. RORα becomes highly expressed in postmitotic Purkinje cells. It regulates their maturation, particularly dendritic differentiation. Dendritogenesis and the expression of several genes, including Shh, Itpr1, Pcp4, Calb1, Pcp2, and Slc1a6, normally expressed in mature Purkinje cells, are inhibited in RORα-deficient mice.	SIGNOR-266847
P11413	P12931	0	phosphorylation	up-regulates activity	0.274	Here, we show that tyrosine kinase c-Src interacts with and phosphorylates G6PD at Tyr 112. This phosphorylation enhances catalytic activity of G6PD by dramatically decreasing its Km value and increasing its Kcat value for substrate glucose-6-phosphate.	SIGNOR-277550
Q9Y4G8	Q00535	0	phosphorylation	up-regulates activity	0.39	Our results demonstrate that the Cdk5-dependent activation of RapGEF2, spatial activation of Rap1 signalling and Rap1-facilitated surface localization of N-cadherin in the upper intermediate zone control neuronal migration and ultimately the architecture of the mammalian cerebral cortex.\|This demonstrates that Cdk5 phosphorylates RapGEF2 at Ser1124 in vitro .	SIGNOR-278258
P42224	Q14164	0	phosphorylation	up-regulates	0.4	All stats are phosphorylated on at least one serine residue in their tad specifically, ser727 in stats 1 and 3 and ser721 in stat4. Stat serine kinases have been identified through the use of inhibitors, dominant-negative alleles, and in vitro kinase assays. They include mapk (p38mapk: stats 1, 3, 4;erk: stat3, 5;jnk: stat3), pkc_ (stat1, stat3), mtor (stat3), nlk (stat3 (42)), and camkii and ikk_ (stat1 (39, 40, 43)).STAT Serine phosphorylation regulates transcriptional activity (see below).	SIGNOR-154775
P06493	O95997	1	phosphorylation	up-regulates	0.598	Hpttg is phosphorylated by cdc2 at ser165 these results suggest that hpttg is induced by, and may have a role in, regulatory pathways involved in the control of cell proliferation.	SIGNOR-74619
Q12778	O00330	1	transcriptional regulation	down-regulates quantity by repression	0.2	Our genetic analysis indicates that Foxo1 is an effector of Irs2 signaling in pancreatic β cells. Foxo1 inactivation leads to increased Pdx1 expression and β cell proliferation. Since Foxo1 is expressed in a subset of cells embedded within pancreatic ducts, we propose that, in quiescent duct-associated cells that are not committed to a β cell fate, Foxo1 acts as a transcriptional brake on Pdx1. We propose the following mechanism of Foxo1 regulation: small quantities of insulin are released in the pancreatic duct (31), where they activate signaling (32) in the Foxo1-positive duct cell subset, leading to Foxo1 nuclear exclusion and Pdx1 expression.	SIGNOR-278151
P01106	P52789	1	transcriptional regulation	up-regulates quantity	0.37	Here, using the P493-6 Burkitt's lymphoma model with an inducible MYC, we demonstrate that HIF-1 cooperates with dysregulated c-Myc to promote glycolysis by induction of hexokinase 2, which catalyzes the first step of glycolysis, and pyruvate dehydrogenase kinase 1, which inactivates pyruvate dehydrogenase and diminishes mitochondrial respiration.	SIGNOR-259986
P62136	O15105	2	binding	up-regulates	0.429	Smad7, induced by alk1 activation, recruits pp1? To alk1 and thereby inhibits tgf-?/Alk1-induced smad1/5 phosphorylation in ecs	SIGNOR-145389
Q12888	Q8N2W9	0	sumoylation	up-regulates	0.637	Pias1 and pias4 are recruited to dna-damage sites and mediate 53bp1 recruitment and sumoylation	SIGNOR-162167
P53779	P61978	1	phosphorylation	up-regulates activity	0.339	JNK Phosphorylation of HnRNP K Increases Its Transcriptional Activity. the primary site for JNK phosphorylation consists of serines 216 and 353 on the K protein.	SIGNOR-250083
P48454	O95644	1	relocalization	up-regulates	0.704	The ca2+ dependent phosphatase calcineurin induces cardiac and skeletal muscle hypertrophy by a process that involves nf-at nuclear translocation, and activation of mef2c.	SIGNOR-179796
Q92574	P28482	0	phosphorylation	down-regulates	0.49	Here, we show that erk may play a critical role in tsc progression through posttranslational inactivation of tsc2. Erk-dependent phosphorylation leads to tsc1-tsc2 dissociation and markedly impairs tsc2 ability to inhibit mtor signalin.	SIGNOR-157162
P24821	P08047	0	transcriptional regulation	up-regulates quantity by expression	0.2	Sp1 and Ets1 are potent transactivators of the TN-C promoter.	SIGNOR-261600
O60341	P78347	0	relocalization	up-regulates activity	0.405	Moreover, the inhibitory effect of TFII-I on transcription is mediated by its ability to recruit corepressor complexes, including histone deacetylase 3 (HDAC3) (25, 133), histone H3K4-specific demethylase LSD1 (48), and components of the polycomb repressor complex	SIGNOR-268540
Q96QE3	P06493	0	phosphorylation	down-regulates activity	0.24	To determine whether mitotic CDK phosphorylates ATAD5, a CDK1 inhibitor (RO3306) was applied to nocodazole-arrested cells (Figure S3F). CDK1 inhibition resulted in a loss of S653 phosphorylation (Figure S3F). These data meant that the S653 residue in the BET BD of ATAD5 is phosphorylated by mitotic CDK. This result suggested that the BRD4-ATAD5 interaction is inhibited during mitosis.	SIGNOR-266410
P56524	Q9Y2K2	0	phosphorylation	down-regulates activity	0.411	They find that SIK3 phosphorylates and inhibits HDAC4 during feeding states.\|They find that SIK3 phosphorylates and inhibits HDAC4 during feeding\nstates.	SIGNOR-279430
P38405	P21728	2	binding	up-regulates activity	0.571	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-256939
O94813	Q96MS0	2	binding	up-regulates activity	0.626	This observation suggests that Slit2 may require the Robo2 and Robo3 receptors in this process . Slit2 causes the miRNA miR-182 to release cofilin1 mRNA, potentiating cofilin1 local translation and resulting in growth cone collapse. The use of morpholinos or RNAi to knockdown robo2 and robo3 in X. laevis RGCs, would be useful to further confirm that Robo2 and Robo3 are the receptors involved in Slit2-dependent cofilin1 translation.	SIGNOR-268381
P15884	P01106	1	transcriptional regulation	up-regulates quantity by expression	0.371	Association of c-Jun, β-catenin, and TCF4 specifically with the downstream enhancer underlies mitogen stimulation of c-Myc transcription.	SIGNOR-253324
Q00987	O94992	1	ubiquitination	up-regulates activity	0.465	Here we report that human double minute-2 protein (HDM2), a p53-specific E3 ubiquitin ligase, specifically ubiquitinates HEXIM1 through the lysine residues located within the basic region of HEXIM1.\|However, the HDM2-induced HEXIM1 ubiquitination does not lead to proteasome-mediated protein degradation.	SIGNOR-278701
Q9GZV5	P49674	0	phosphorylation	down-regulates	0.366	LATS1/2-mediated phosphorylation of a conserved serine in this region (Ser311 in human TAZ; Ser397 in human YAP) primes for further phosphorylation by CK1_/_ kinases (Ser314 on human TAZ; Ser400/403 in human YAP)	SIGNOR-230747
Q8IWB6	P06493	0	phosphorylation	down-regulates quantity by destabilization	0.333	Cdk1 phosphorylation of Tex14 is required for the Tex14-Plk1 interaction	SIGNOR-273524
P06748	O15111	0	phosphorylation	up-regulates activity	0.2	S125A and a delta form lacking the aa 119-195 region completely abolished NPM phosphorylation by IKKalpha (XREF_FIG), suggesting that IKKalpha phosphorylates S125 of NPM.\|We found that TNFalpha treatment induced IKKalpha phosphorylation and increased NPM hexamers, which were correlated with increased NPM phosphorylation (XREF_FIG).	SIGNOR-279405
P35638	Q16539	0	phosphorylation	up-regulates activity	0.61	CHOP, a member of the C/EBP family of transcription factors, mediates effects of cellular stress on growth and differentiation. It accumulates under conditions of stress and undergoes inducible phosphorylation on two adjacent serine residues (78 and 81). In vitro, CHOP is phosphorylated on these residues by p38 mitogen-activated protein kinase (MAP kinase).	SIGNOR-250096
P45983	Q16621	1	phosphorylation	down-regulates quantity by destabilization	0.411	Through use of different approaches including nano-scale proteomics, we show that activated-JNK, or Phospho-JNK (P-JNK), physically interacts with p45/NF-E2 and phosphorylates its Ser157 residue. This reaction leads to the poly-ubiquitination of p45/NF-E2 at one or more of six Lys residues, one of which being also a sumoylation site, and its degradation through the proteasome pathway.	SIGNOR-275552
O15455	P12931	0	phosphorylation	up-regulates activity	0.526	Markedly, Src mediated late TLR3 Pi-Tyr759 leads to the nuclear accumulation of IRF3 and IRF7 and the increase of IFN-beta production.\|Src can directly phosphorylate TLR3 Tyr759 in\nvitro and in vivo .	SIGNOR-279657
O95841	Q02763	2	binding	up-regulates	0.506	In experiments with human endothelial cell lines, ang3 was identified as an antagonist of tie2 and ang4 was identified as an agonist of tie2.	SIGNOR-127354
Q99717	Q9UPW6	1	transcriptional regulation	up-regulates quantity	0.259	Chromatin immunoprecipitation (ChIP) revealed a subset of the BIG (BMP4 induced genes) signature, including Satb2, Smad6, Hand1, Gadd45γ and Gata3, that was bound by Smad1/5 in the developing mandible, revealing direct Smad-mediated regulation	SIGNOR-268939
P35222	P49768	2	binding	down-regulates	0.808	Importantly, our data show that binding of ps1 to cadherin mediates the effects of ps1 on the phosphorylation, ubiquitination, and destabilization of beta-catenin. Thus, cadherins mediate both the association of ps1 and beta-catenin and the effects of ps1 on the cellular levels of beta-catenin	SIGNOR-22837
Q16665	Q9H4B4	0	phosphorylation	down-regulates	0.348	Polo-like kinase 3 functions as a tumor suppressor and is a negative regulator of hypoxia-inducible factor-1 alpha under hypoxic conditionsplk3 can potentially inhibit hif-1_ by physical interaction and direct phosphorylation	SIGNOR-178743
Q92934	Q9P286	0	phosphorylation	down-regulates activity	0.2	P21-Activated kinase 5 (Pak5) localizes to mitochondria and inhibits apoptosis by phosphorylating BAD. Pak5 phosphorylates BAD Ser-112	SIGNOR-250247
P17706	P42229	1	dephosphorylation	down-regulates activity	0.733	Upon ligand binding, IL-2R , IL-6R or LeptinR , IFN-_R , IFN-_R and PRLR or growth hormone (GH) receptor associated JAKs become activated. These JAKs mediate phosphorylation of specific tyrosine residues and recruit STATs. Activated STATs are released from the receptor and translocate to the nucleus. PTP1B dephosphorylates JAK2, TYK2 and STAT5 . The 45-kDa form of TC-PTP was shown to dephosphorylate JAK1 and JAK3 as well as STAT1, STAT3 and STAT5.	SIGNOR-133547
P00533	O60674	0	phosphorylation	up-regulates activity	0.612	Tyrosine at residue 1,068 of the EGFR is proposed to be one of the principal phosphorylation sites and Grb2-binding sites stimulated by growth hormone via Jak2. Our results indicate that the role of EGFR in signalling by growth hormone is to be phosphorylated by Jak2, thereby providing docking sites for Grb2 and activating MAP kinases and gene expression, independently of the intrinsic tyrosine kinase activity of EGFR.¬†	SIGNOR-251347
P84243	Q9NRC8	0	deacetylation	up-regulates activity	0.2	SIRT7 links H3K18 deacetylation to maintenance of oncogenic transformation.\|Genome-wide binding studies reveal that SIRT7 binds to promoters of a specific set of gene targets, where it deacetylates H3K18Ac and promotes transcriptional repression.	SIGNOR-275872
P56945	Q14289	0	phosphorylation	up-regulates activity	0.782	Pyk2 knockdown also decreased p130Cas.\|p130Cas and paxillin can be phosphorylated by Fak or Pyk2, and bind directly to these kinases.	SIGNOR-280100
Q9P2S2	Q9NZ94	2	binding	up-regulates activity	0.83	Pre- and postsynaptic plasma membranes are always precisely aligned, and are separated by a synaptic cleft of ~20 nm. The cleft contains an undefined proteinaceous material in the middle, and is presumably bridged by synaptic cell-adhesion molecules such as Nrxns and Nlgns that align the pre- and postsynaptic elements and mediate trans-synaptic signaling.\|Nlgns bind to both alpha- and beta-Nrxns with nanomolar affinities; binding involves the sixth LNS-domain of alpha-Nrxns which corresponds to the only LNS-domain of beta-Nrxns52. The binding affinities differ characteristically between various pairs of Nlgns and Nrxns, and are controlled by alternative splicing of both Nrxns and Nlgns (Figure 1c)	SIGNOR-264152
P24385	P35222	0	transcriptional regulation	up-regulates quantity by expression	0.801	One of the most well studied activators of CCND1 transcription is β-catenin, which could be actived by AKT signalling to inducing G1/S transition. When β-catenin is translocated from the cytoplasm to the nucleus, it forms a complex with the ternary complex factor (TCF) and/or lymphoid enhancer-binding factor (LEF) and stimulates cyclin D1 gene transcription (Fig. 4C).In agreement with the data described above, a chromatin immunoprecipitation (ChIP) assay confirmed that TNC regulates the binding of β-catenin to the TCF/LEF-binding site in the CCND1 promoter (Fig. 4C). Additionally, the β-cateninbinding activity with respect to the CCND1 promoter was much higher in TNC-overexpression PANC-1 cells than in the vector controls.	SIGNOR-277738
P02686	P09543	0	null	down-regulates activity	0.455	We provide evidence that CNP directly associates with and organizes the actin cytoskeleton, thereby providing an intracellular strut that counteracts membrane compaction by myelin basic protein (MBP).	SIGNOR-269269
P62942	P36897	2	binding	down-regulates activity	0.853	Blocking fkbp12/type i receptor interaction with fk506 nonfunctional derivatives enhances the ligand activity, indicating that fkbp12 binding is inhibitory to the signaling pathways of the tgf beta family ligands	SIGNOR-236142
Q13535	O14757	1	phosphorylation	up-regulates	0.925	Atr activation typically leads to chk1 phosphorylation and activation. In response to genotoxic stress, chk1 is phosphorylated on serines 317 (s317) and 345 (s345) by the ataxia-telangiectasia-related (atr) protein kinase.	SIGNOR-134716
Q92993	Q00987	0	polyubiquitination	down-regulates quantity by destabilization	0.654	Furthermore, we provide evidence that Mdm2, the ubiquitin ligase of the p53 tumour suppressor, interacts physically with Tip60 and induces its ubiquitylation and proteasome-dependent degradation.	SIGNOR-272613
Q6UXS9	P55211	1	cleavage	up-regulates	0.2	Caspase-12 specifically cleaves and activates procaspase-9 in cytosolic extracts. Results suggest that caspase-12 can activate caspase-9 without involvement of cytochromec.	SIGNOR-90318
Q7Z570	Q13489	1	transcriptional regulation	down-regulates quantity by repression	0.2	ZNF804A has been implicated in susceptibility to schizophrenia by several genome-wide association studies (GWAS), follow-up association studies and meta-analyses. ZNF804A was identified as a schizophrenia-associated gene by GWAS and was predicted to play a role in DNA binding and transcription To identify the genes that are affected by ZNF804A, we manipulated the expression of the ZNF804A protein in HEK293 human embryonic kidney cell lines and performed a cDNA microarray analysis followed by qPCR. We found that ZNF804A-overexpression up-regulated four genes (ANKRD1, INHBE, PIK3AP1, and DDIT3) and down-regulated three genes (CLIC2, MGAM, and BIRC3).	SIGNOR-269467
Q92934	P06493	0	phosphorylation	up-regulates activity	0.2	CDK1-mediated Bcl-2 serine 70 phosphorylation enhances its pro-apoptotic function, whereas CDK1-mediated Bad serine 128 phosphorylation promotes apoptosis.	SIGNOR-267921
Q13258	P38405	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-256898
O43557	Q92956	2	binding	up-regulates	0.857	A member of the tumor necrosis factor (tnf) superfamily, human tnfsf14 (htnfsf14)/hvem-l (herpes virus entry mediator ligand) was isolated as a cellular ligand for hvem/tr2 and human lymphotoxin beta receptor (ltbetar). Tnfsf14 induces apoptosis and suppresses tumor formation	SIGNOR-79328
Q12857	A6NFN3	1	transcriptional regulation	up-regulates quantity	0.261	For example, within the NFI targetome, we identified 6 collagen genes, 13 genes encoding potassium channel or glutamate receptor subunits and a range of factors related to axon guidance (e.g. Slit1, Robo1, Epha4, Epha5, Epha8)	SIGNOR-268911
P10451	P56178	0	transcriptional regulation	up-regulates quantity	0.373	Dlx5 initiates a complete osteogenic differentiation in these early primary cells, by triggering Runx2, osteopontin, alkaline phosphatase, and other gene expression according to the sequential temporal sequence observed during skull osteogenesis in vivo.	SIGNOR-245340
P17252	P52565	1	phosphorylation	down-regulates activity	0.449	PKCalpha phosphorylates RhoGDIalpha at Ser34 to reduce its affinity for RhoA (but not for Rac1 or Cdc42) .	SIGNOR-279097
O00187	P06681	1	cleavage	up-regulates activity	0.436	The MASPs in the preparations had proteolytic activities against C4, C2, and C3 in the fluid phase	SIGNOR-263416
Q12778	Q13043	0	phosphorylation	up-regulates	0.595	Bonni and coworkers demonstrated that mst1 can phosphorylate foxo3 (and subsequently, foxo1) principally ser207 (ser212 in foxo1), a conserved site in the forkhead domain. This phosphorylation interdicts 14-3-3 binding, promotes foxo nuclear residence and transcriptional activity. The other major signaling modules that directly regulate the activity of the foxo factors include the stress-activated jun-n-terminal kinase (jnk), the mammalian ortholog of the ste20-like protein kinase (mst1), and the deacetylase sirt1.	SIGNOR-191847
Q96RI1	P17252	0	phosphorylation	up-regulates	0.325	Phosphorylation of farnesoid x receptor by protein kinase c promotes its transcriptional activity. pkcalpha phosphorylates in vitro fxr in its dna-binding domain on s135 and s154.	SIGNOR-180537
Q96KB5	P12931	0	phosphorylation	up-regulates quantity by stabilization	0.395	Phosphorylation of TOPK at Y74, Y272 by Src increases the stability of TOPK and promotes tumorigenesis of colon	SIGNOR-277217
Q15139	O60602	1	phosphorylation	up-regulates	0.353	Pkd phosphorylated the tlr5-derived target peptide in vitro, and phosphorylation of the putative target serine 805 in hek 293t cell-derived tlr5 was identified by mass spectrometry. These results demonstrate that both pkd1 and pkd2 are required for inflammatory responses following tlr2, tlr4, or tlr5 activation, although pkd1 is more strongly involved	SIGNOR-154473
P28562	Q13950	1	dephosphorylation	up-regulates activity	0.353	In a separate study, MKP-1 was shown to induce osteogenesis by dephosphorylating Ser125 on Runx2 isoform type II (37).\|MKP-1 increases RUNX2 activity and downregulates MAPK, cyclin D1 in differentiated osteoblasts inducing growth arrest and mineralization.	SIGNOR-277143
P68400	P11831	1	phosphorylation	up-regulates activity	0.552	Casein kinase II (CKII) phosphorylates the mammalian transcription factor serum response factor (SRF) on a serine residue(s) located within a region of the protein spanning amino acids 70 to 92, thereby enhancing its DNA-binding activity in vitro.\| Nevertheless, additional mutation of serines 77 and 79 was required before phosphorylation and enhanced binding were completely abolished. Thus, serines 77 and 79 could also be recognized by CKII if serines 83 and 85 were mutated.	SIGNOR-250955
Q86XR7	O00206	2	binding	up-regulates	0.733	Mappit analysis of early toll-like receptor signalling events.	SIGNOR-160424
Q5S007	P46734	1	phosphorylation	up-regulates activity	0.393	LRRK2 phosphorylates MKK3 and MKK7 in vitro but has a relatively minor effect on MKK6 phosphorylation.	SIGNOR-279057
P51530	O96017	0	phosphorylation	up-regulates activity	0.526	We later observed that Dna2 phosphorylation by Cds1 is necessary for Dna2 association with chromatin in HU treated cells.	SIGNOR-279729
P33176	Q9NRI5	2	binding	up-regulates activity	0.2	We identified Kinesin-1, a microtubule-dependent and plus-end directed motor, as a DISC1-interacting molecule. Our results show that DISC1 links Kinesin-1 to the NUDEL/LIS1/14-3-3ε complex, serves as the cargo receptor, and regulates the transport of the complex to axons, leading to axon elongation. DISC1 directly interacted with kinesin heavy chain of Kinesin-1. Kinesin-1 interacted with the NUDEL/LIS1/14-3-3ε complex through DISC1	SIGNOR-252161
P08709	P38435	0	carboxylation	up-regulates activity	0.688	Thus, vitamin K acts as a cofactor for GGCX via the vitamin K cycle and exerts physiological effects through its regulation of VKDPs [29]. More than 20 VKDPs have been found. Osteocalcin promotes bone formation, and blood coagulation factors II, VII, IX, and X activate blood coagulation. Matrix Gla protein suppresses cardiovascular calcification, and brain-expressed Gas 6 promotes neural differentiation [29]. GGCX is an enzyme that converts glutamic acid (Glu) residues to Gla residues, so that the Gla-containing proteins can exert various physiological actions such as blood coagulation and bone formation.	SIGNOR-265919
Q99933	P11142	2	binding	up-regulates activity	0.895	Heat shock cognate protein 70 (Hsc70) regulates protein homeostasis through its reversible interactions with client proteins. Hsc70 has two major domains: a nucleotide-binding domain (NBD), that hydrolyzes ATP, and a substrate-binding domain (SBD), where clients are bound. Members of the BAG family of co-chaperones, including Bag1 and Bag3, are known to accelerate release of both ADP and client from Hsc70.	SIGNOR-254115
Q9Y478	Q92786	1	phosphorylation	down-regulates quantity by destabilization	0.2	Furthermore, the Ser79 phosphorylation of PROX1 by AMPK enhances the recruitment of CUL4-DDB1 ubiquitin ligase to promote PROX1 degradation.	SIGNOR-277609
Q9H334	Q9P283	1	transcriptional regulation	down-regulates quantity by repression	0.33	FoxP1 stimulates angiogenesis by repressing the inhibitory guidance protein semaphorin 5B in endothelial cells.	SIGNOR-269050

Q13546

P23458

0

phosphorylation

up-regulates activity

0.2

In addition , our results suggest JAK1 could be recruited to TNF-RSC to modulate RIPK1 activity .|In this study, we show that non-receptor tyrosine kinases JAK1 and SRC could phosphorylate RIPK1 on tyrosine 384 (Y384) in human RIPK1 (Y383 in mouse RIPK1), and serve as essential regulators of RIPK1 in the TNFR1 signaling pathway.

SIGNOR-278948

P50461

P15172

2

binding

up-regulates activity

0.468

we found that nuclear MLP functions through a physical interaction with the muscle basic helix-loop-helix (bHLH) transcription factors MyoD, MRF4, and myogenin. we propose that it serves as a cofactor for the myogenic bHLH proteins by increasing their interaction with specific DNA regulatory elements.

SIGNOR-241116

P12755

Q6ZNA4

0

ubiquitination

down-regulates

0.595

On tgf-beta treatment, the e3 ubiquitin ligase arkadia mediates degradation of ski in a smad-dependent manner

SIGNOR-178598

P31749

Q6ZVD8

0

dephosphorylation

down-regulates

0.773

Here, we identify a protein phosphatase, ph domain leucine-rich repeat protein phosphatase (phlpp), that specifically dephosphorylates the hydrophobic motif of akt (ser473 in akt1), triggering apoptosis and suppressing tumor growth.[...] These data are consistent with phlpp terminating akt signaling by directly dephosphorylating and inactivating akt.

SIGNOR-252602

Q9UBE8

P10242

1

phosphorylation

down-regulates activity

0.714

Furthermore, the downregulation of c-Myb by NLK overexpression could be inhibited in cells that had been treated with the 26S proteasome inhibitor MG132 but not in those treated with DMSO ( ).|HIPK2 and NLK directly bind to c-Myb, and NLK phosphorylates c-Myb at multiple sites, resulting in its ubiquitination and proteasome-dependent degradation [32].

SIGNOR-280049

Q8WV16

Q9NRC1

2

binding

down-regulates quantity by destabilization

0.2

We found that both CUL4A and CUL4B can form an E3 complex with DNA damage-binding protein 1 (DDB1) and DDB1-CUL4-associated factor 4 (DCAF4). In vitro and in vivo ubiquitination analyses indicate that CRL4DCAF4 E3 ligase specifically directs degradation of ST7 (suppression of tumorigenicity 7).

SIGNOR-272303

P01903

P48382

0

transcriptional regulation

up-regulates quantity by expression

0.503

In this report, we correlate the loss of IFN-γ induction of MHC class II genes with the identification of a molecular defect in an essential regulator, namely RFX5. | We have further confirmed this finding by showing that new RFX5 leucine mutants created in vitro are incapable of transactivating a class II promoter, suggesting the identification of residues essential for RFX activity.

SIGNOR-266228

O75496

Q9H211

2

binding

down-regulates activity

0.972

Here we show that geminin interacts tightly with Cdt1, a recently identified replication initiation factor necessary for MCM loading.

SIGNOR-261680

Q8WWN8

P63000

1

gtpase-activating protein

down-regulates activity

0.47

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-260456

P02511

P22914

2

binding

up-regulates activity

0.538

Human gamma-crystallins are long-lived, unusually stable proteins of the eye lens exhibiting duplicated, double Greek key domains. The lens also contains high concentrations of the small heat shock chaperone alpha-crystallin, which suppresses aggregation of model substrates in vitro. Mature-onset cataract is believed to represent an aggregated state of partially unfolded and covalently damaged crystallins. The alphaB-crystallin oligomers formed long-lived stable complexes with their gammaD-crystallin substrates. These in vitro results provide support for protein unfolding/protein aggregation models for cataract, with alpha-crystallin suppressing aggregation of damaged or unfolded proteins through early adulthood but becoming saturated with advancing age.

SIGNOR-253623

P23467

Q02763

1

dephosphorylation

down-regulates activity

0.555

Simultaneous inhibition of Tie2 cleavage and VE-PTP synergistically enhances Tie2 activation by up to 10-fold (Fig. 7A).|Tie2 activation is also importantly regulated by vascular endothelial protein tyrosine phosphatase (VE-PTP), which dephosphorylates Tie2 to inhibit its vascular stabilizing effects .|Tie2 activation is also importantly regulated by vascular endothelial protein tyrosine phosphatase (VE-PTP), which dephosphorylates Tie2 to inhibit its vascular stabilizing effects.

SIGNOR-277059

O75475

P42574

0

cleavage

down-regulates

0.348

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

SIGNOR-180144

Q96GM5

Q96EP1

0

polyubiquitination

down-regulates quantity by destabilization

0.307

Here we report that CHFR interacts with BRG1, SNF5, and BAF60a of the SWI/SNF-like BAF complex and ubiquitinates them to target for degradation through a proteasome-mediated pathway, and that SRG3/mBAF155 stabilizes these components by blocking their interaction with CHFR. These results suggest that CHFR enhances the degradation of the components of the SWI/SNF-like BAF complex by inducing their poly-ubiquitination.

SIGNOR-271459

P01236

P31270

0

transcriptional regulation

up-regulates quantity by expression

0.351

HoxA-11 enhanced upregulation of PRL only in differentiated cells.

SIGNOR-261630

O95837

P25100

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-257191

P08754

P08908

2

binding

up-regulates activity

0.57

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-256836

P08253

Q13753

1

cleavage

up-regulates activity

0.471

Induction of Cell Migration by Matrix Metalloprotease-2 Cleavage of Laminin-5|MMP2 cleaved the Ln-5 gamma2 subunit at residue 587, exposing a putative cryptic promigratory site on Ln-5 that triggers cell motility. This altered form of Ln-5 is found in tumors and in tissues undergoing remodeling, but not in quiescent tissues. Cleavage of Ln-5 by MMP2 and the resulting activation of the Ln-5 cryptic site may provide new targets for modulation of tumor cell invasion and tissue remodeling.

SIGNOR-253240

P29966

Q16512

0

phosphorylation

down-regulates activity

0.365

PRK1 phosphorylates MARCKS at the PKC sites: serine 152, serine 156 and serine 163.

SIGNOR-249671

P50406

P50148

2

binding

up-regulates activity

0.344

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-257340

Q92952

P00533

0

phosphorylation

up-regulates activity

0.2

These results demonstrate the novel information that hSKCa1 channels are inhibited by genistein, T25 and AG556 via EGFR tyrosine kinase inhibition, which is related to the phosphorylation of Tyr(109) in the N-terminus.

SIGNOR-276490

Q02750

P10398

0

phosphorylation

up-regulates

0.74

Our data demonstrated that a-raf is, indeed, a mek1 activator and may play a role in growth factor signaling|The immunoprecipitates were assayed for GST-MEK1 activation. D, activation of MEK1 by A-Raf requires the presence of serine residue 218 and 222.

SIGNOR-235944

P27986

P03372

2

binding

up-regulates

0.628

Recently, it has been known that er activates phosphatidylinositol-3-oh kinase (pi3k) through binding with the p85 regulatory subunit of pi3k.

SIGNOR-140470

O14836

Q9Y275

2

binding

up-regulates

0.781

Tumor necrosis factor (tnf) receptor superfamily member taci is a high affinity receptor for tnf family members april and blys.

SIGNOR-81360

Q96PZ7

P0C0L5

2

binding

down-regulates quantity

0.2

CUB and sushi multiple domains 1 (CSMD1) is a relatively poorly studied large transmembrane protein of 390 kDa composed of 14 N-terminal CUB domains interspersed with complement control protein (CCP) domains followed by 15 consecutive CCP domains. The active domains of CSMD1 were then identified in CCP17-21, which were shown to interact with C4b and C3b and present these complement proteins for degradation by factor

SIGNOR-265149

Q99835

Q9UMX1

2

binding

down-regulates activity

0.64

In addition to activating g(i), smo signals through its c-terminal tail to inhibit suppressor of fused, resulting in stabilization and activation of the gli family of transcription factors, which execute a transcriptional response to so-called canonical hh signaling.

SIGNOR-177656

Q9UNE7

O14654

1

polyubiquitination

down-regulates quantity by destabilization

0.2

IRS4 was phosphorylated at Ser859 by CK1γ2 in vitro and in vivo, which promoted the polyubiquitination and degradation of IRS4 through the ubiquitin/lysosome pathway by the carboxyl terminus of Hsc70-interacting protein(CHIP).

SIGNOR-277616

Q13131

P17252

0

phosphorylation

down-regulates activity

0.2

Purified PKC and Akt both phosphorylated AMPKα1 Ser487 in vitro with similar efficiency. PKC activation was associated with reduced AMPK activity, as inhibition of PKC increased AMPK activity and phorbol esters inhibited AMPK, an effect lost in cells expressing mutant AMPKα1 Ser487Ala. Consistent with a pathophysiological role for this modification, AMPKα1 Ser487 phosphorylation was inversely correlated with insulin sensitivity in human muscle.

SIGNOR-276459

P09619

P00519

2

phosphorylation

up-regulates activity

0.527

Here, we show that PDGFR-beta-phosphorylation of Abl kinases has functional consequences as PDGFR-beta phosphorylates Abl kinases on Y245 and Y412, sites known to be required for activation of Abl kinases.

SIGNOR-278319

P12931

Q13322

1

phosphorylation

down-regulates

0.447

Grb10 tyrosine phosphorylation was stimulated by expression of constitutively active src or fyn in cells and by incubation with purified src or fyn in vitro. The insulin stimulated or src/fyn-mediated tyrosine phosphorylation in vivo was significantly reduced when grb10 tyrosine 67 was changed to glycine. This mutant form of grb10 bound with higher affinity to the ir in cells than that of the wild-type protein, suggesting that tyrosine phosphorylation of grb10 may normally negatively regulate its binding to the ir.

SIGNOR-78706

Q14653

P55286

0

transcriptional regulation

up-regulates quantity

0.2

CHD8 binds to histone H3 di- and trimethylated on lysine 4. It resides on the human U6 promoter as well as the mRNA IRF3 promoter in vivo and contributes to efficient transcription from both these promoters

SIGNOR-266898

P06213

Q13480

1

phosphorylation

up-regulates activity

0.502

HGab-1 was phosphorylated by IR at eight tyrosine residues (Y242, Y285, Y373, Y447, Y472, Y619, Y657, and Y689). t Gab-1 is the major binding partner of PI-3 kinase in 3T3L1 cells when stimulated with insulin

SIGNOR-251310

Q16827

P07948

1

dephosphorylation

down-regulates activity

0.325

Both Lyn and ZAP70 were dephosphorylated by wild-type PTPROt, but not by its catalytic site mutant.|Lyn kinase and ZAP70 are substrates of PTPROt in B-cells: Lyn inactivation by PTPROt sensitizes leukemia cells to VEGF-R inhibitor pazopanib.

SIGNOR-277144

Q9P0U3

P31749

1

desumoylation

down-regulates quantity by destabilization

0.28

Although multiple sites on Akt could be SUMOylated, K276 was identified as a major SUMO acceptor site. K276R or E278A mutation reduced SUMOylation of Akt but had little effect on its ubiquitination. Strikingly, these mutations also completely abolished Akt kinase activity. In support of these results, we found that expression of PIAS1 and SUMO1 increased Akt activity, whereas expression of SENP1 reduced Akt1 activity.

SIGNOR-252736

O14757

P19838

1

phosphorylation

down-regulates

0.275

Taken together, the above findings suggest that chk1 phosphorylates p50 at s329 and further, that this phosphorylation blocks p50 dna binding.

SIGNOR-195208

Q9Y5I2

Q9UN70

2

binding

up-regulates activity

0.2

The clustered protocadherins comprise the largest subfamily of the cadherin superfamily and are predominantly expressed in the nervous system. Pcdh-alpha proteins interact with beta1-integrin to promote cell adhesion. They also form oligomers with Pcdh-gamma proteins at the same membrane sites.

SIGNOR-265696

P08754

Q15391

2

binding

up-regulates activity

0.403

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-256866

Q14643

P35398

0

transcriptional regulation

up-regulates quantity by expression

0.242

RORα regulates the expression of several genes in Purkinje cells. RORα becomes highly expressed in postmitotic Purkinje cells. It regulates their maturation, particularly dendritic differentiation. Dendritogenesis and the expression of several genes, including Shh, Itpr1, Pcp4, Calb1, Pcp2, and Slc1a6, normally expressed in mature Purkinje cells, are inhibited in RORα-deficient mice.

SIGNOR-266847

P11413

P12931

0

phosphorylation

up-regulates activity

0.274

Here, we show that tyrosine kinase c-Src interacts with and phosphorylates G6PD at Tyr 112. This phosphorylation enhances catalytic activity of G6PD by dramatically decreasing its Km value and increasing its Kcat value for substrate glucose-6-phosphate.

SIGNOR-277550

Q9Y4G8

Q00535

0

phosphorylation

up-regulates activity

0.39

Our results demonstrate that the Cdk5-dependent activation of RapGEF2, spatial activation of Rap1 signalling and Rap1-facilitated surface localization of N-cadherin in the upper intermediate zone control neuronal migration and ultimately the architecture of the mammalian cerebral cortex.|This demonstrates that Cdk5 phosphorylates RapGEF2 at Ser1124 in vitro .

SIGNOR-278258

P42224

Q14164

0

phosphorylation

up-regulates

0.4

All stats are phosphorylated on at least one serine residue in their tad specifically, ser727 in stats 1 and 3 and ser721 in stat4. Stat serine kinases have been identified through the use of inhibitors, dominant-negative alleles, and in vitro kinase assays. They include mapk (p38mapk: stats 1, 3, 4;erk: stat3, 5;jnk: stat3), pkc_ (stat1, stat3), mtor (stat3), nlk (stat3 (42)), and camkii and ikk_ (stat1 (39, 40, 43)).STAT Serine phosphorylation regulates transcriptional activity (see below).

SIGNOR-154775

P06493

O95997

1

phosphorylation

up-regulates

0.598

Hpttg is phosphorylated by cdc2 at ser165 these results suggest that hpttg is induced by, and may have a role in, regulatory pathways involved in the control of cell proliferation.

SIGNOR-74619

Q12778

O00330

1

transcriptional regulation

down-regulates quantity by repression

0.2

Our genetic analysis indicates that Foxo1 is an effector of Irs2 signaling in pancreatic β cells. Foxo1 inactivation leads to increased Pdx1 expression and β cell proliferation. Since Foxo1 is expressed in a subset of cells embedded within pancreatic ducts, we propose that, in quiescent duct-associated cells that are not committed to a β cell fate, Foxo1 acts as a transcriptional brake on Pdx1. We propose the following mechanism of Foxo1 regulation: small quantities of insulin are released in the pancreatic duct (31), where they activate signaling (32) in the Foxo1-positive duct cell subset, leading to Foxo1 nuclear exclusion and Pdx1 expression.

SIGNOR-278151

P01106

P52789

1

transcriptional regulation

up-regulates quantity

0.37

Here, using the P493-6 Burkitt's lymphoma model with an inducible MYC, we demonstrate that HIF-1 cooperates with dysregulated c-Myc to promote glycolysis by induction of hexokinase 2, which catalyzes the first step of glycolysis, and pyruvate dehydrogenase kinase 1, which inactivates pyruvate dehydrogenase and diminishes mitochondrial respiration.

SIGNOR-259986

P62136

O15105

2

binding

up-regulates

0.429

Smad7, induced by alk1 activation, recruits pp1? To alk1 and thereby inhibits tgf-?/Alk1-induced smad1/5 phosphorylation in ecs

SIGNOR-145389

Q12888

Q8N2W9

0

sumoylation

up-regulates

0.637

Pias1 and pias4 are recruited to dna-damage sites and mediate 53bp1 recruitment and sumoylation

SIGNOR-162167

P53779

P61978

1

phosphorylation

up-regulates activity

0.339

JNK Phosphorylation of HnRNP K Increases Its Transcriptional Activity. the primary site for JNK phosphorylation consists of serines 216 and 353 on the K protein.

SIGNOR-250083

P48454

O95644

1

relocalization

up-regulates

0.704

The ca2+ dependent phosphatase calcineurin induces cardiac and skeletal muscle hypertrophy by a process that involves nf-at nuclear translocation, and activation of mef2c.

SIGNOR-179796

Q92574

P28482

0

phosphorylation

down-regulates

0.49

Here, we show that erk may play a critical role in tsc progression through posttranslational inactivation of tsc2. Erk-dependent phosphorylation leads to tsc1-tsc2 dissociation and markedly impairs tsc2 ability to inhibit mtor signalin.

SIGNOR-157162

P24821

P08047

0

transcriptional regulation

up-regulates quantity by expression

0.2

Sp1 and Ets1 are potent transactivators of the TN-C promoter.

SIGNOR-261600

O60341

P78347

0

relocalization

up-regulates activity

0.405

Moreover, the inhibitory effect of TFII-I on transcription is mediated by its ability to recruit corepressor complexes, including histone deacetylase 3 (HDAC3) (25, 133), histone H3K4-specific demethylase LSD1 (48), and components of the polycomb repressor complex

SIGNOR-268540

Q96QE3

P06493

0

phosphorylation

down-regulates activity

0.24

To determine whether mitotic CDK phosphorylates ATAD5, a CDK1 inhibitor (RO3306) was applied to nocodazole-arrested cells (Figure S3F). CDK1 inhibition resulted in a loss of S653 phosphorylation (Figure S3F). These data meant that the S653 residue in the BET BD of ATAD5 is phosphorylated by mitotic CDK. This result suggested that the BRD4-ATAD5 interaction is inhibited during mitosis.

SIGNOR-266410

P56524

Q9Y2K2

0

phosphorylation

down-regulates activity

0.411

They find that SIK3 phosphorylates and inhibits HDAC4 during feeding states.|They find that SIK3 phosphorylates and inhibits HDAC4 during feeding\nstates.

SIGNOR-279430

P38405

P21728

2

binding

up-regulates activity

0.571

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-256939

O94813

Q96MS0

2

binding

up-regulates activity

0.626

This observation suggests that Slit2 may require the Robo2 and Robo3 receptors in this process . Slit2 causes the miRNA miR-182 to release cofilin1 mRNA, potentiating cofilin1 local translation and resulting in growth cone collapse. The use of morpholinos or RNAi to knockdown robo2 and robo3 in X. laevis RGCs, would be useful to further confirm that Robo2 and Robo3 are the receptors involved in Slit2-dependent cofilin1 translation.

SIGNOR-268381

P15884

P01106

1

transcriptional regulation

up-regulates quantity by expression

0.371

Association of c-Jun, β-catenin, and TCF4 specifically with the downstream enhancer underlies mitogen stimulation of c-Myc transcription.

SIGNOR-253324

Q00987

O94992

1

ubiquitination

up-regulates activity

0.465

Here we report that human double minute-2 protein (HDM2), a p53-specific E3 ubiquitin ligase, specifically ubiquitinates HEXIM1 through the lysine residues located within the basic region of HEXIM1.|However, the HDM2-induced HEXIM1 ubiquitination does not lead to proteasome-mediated protein degradation.

SIGNOR-278701

Q9GZV5

P49674

0

phosphorylation

down-regulates

0.366

LATS1/2-mediated phosphorylation of a conserved serine in this region (Ser311 in human TAZ; Ser397 in human YAP) primes for further phosphorylation by CK1_/_ kinases (Ser314 on human TAZ; Ser400/403 in human YAP)

SIGNOR-230747

Q8IWB6

P06493

0

phosphorylation

down-regulates quantity by destabilization

0.333

Cdk1 phosphorylation of Tex14 is required for the Tex14-Plk1 interaction

SIGNOR-273524

P06748

O15111

0

phosphorylation

up-regulates activity

0.2

S125A and a delta form lacking the aa 119-195 region completely abolished NPM phosphorylation by IKKalpha (XREF_FIG), suggesting that IKKalpha phosphorylates S125 of NPM.|We found that TNFalpha treatment induced IKKalpha phosphorylation and increased NPM hexamers, which were correlated with increased NPM phosphorylation (XREF_FIG).

SIGNOR-279405

P35638

Q16539

0

phosphorylation

up-regulates activity

0.61

CHOP, a member of the C/EBP family of transcription factors, mediates effects of cellular stress on growth and differentiation. It accumulates under conditions of stress and undergoes inducible phosphorylation on two adjacent serine residues (78 and 81). In vitro, CHOP is phosphorylated on these residues by p38 mitogen-activated protein kinase (MAP kinase).

SIGNOR-250096

P45983

Q16621

1

phosphorylation

down-regulates quantity by destabilization

0.411

Through use of different approaches including nano-scale proteomics, we show that activated-JNK, or Phospho-JNK (P-JNK), physically interacts with p45/NF-E2 and phosphorylates its Ser157 residue. This reaction leads to the poly-ubiquitination of p45/NF-E2 at one or more of six Lys residues, one of which being also a sumoylation site, and its degradation through the proteasome pathway.

SIGNOR-275552

O15455

P12931

0

phosphorylation

up-regulates activity

0.526

Markedly, Src mediated late TLR3 Pi-Tyr759 leads to the nuclear accumulation of IRF3 and IRF7 and the increase of IFN-beta production.|Src can directly phosphorylate TLR3 Tyr759 in\nvitro and in vivo .

SIGNOR-279657

O95841

Q02763

2

binding

up-regulates

0.506

In experiments with human endothelial cell lines, ang3 was identified as an antagonist of tie2 and ang4 was identified as an agonist of tie2.

SIGNOR-127354

Q99717

Q9UPW6

1

transcriptional regulation

up-regulates quantity

0.259

Chromatin immunoprecipitation (ChIP) revealed a subset of the BIG (BMP4 induced genes) signature, including Satb2, Smad6, Hand1, Gadd45γ and Gata3, that was bound by Smad1/5 in the developing mandible, revealing direct Smad-mediated regulation

SIGNOR-268939

P35222

P49768

2

binding

down-regulates

0.808

Importantly, our data show that binding of ps1 to cadherin mediates the effects of ps1 on the phosphorylation, ubiquitination, and destabilization of beta-catenin. Thus, cadherins mediate both the association of ps1 and beta-catenin and the effects of ps1 on the cellular levels of beta-catenin

SIGNOR-22837

Q16665

Q9H4B4

0

phosphorylation

down-regulates

0.348

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

SIGNOR-178743

Q92934

Q9P286

0

phosphorylation

down-regulates activity

0.2

P21-Activated kinase 5 (Pak5) localizes to mitochondria and inhibits apoptosis by phosphorylating BAD. Pak5 phosphorylates BAD Ser-112

SIGNOR-250247

P17706

P42229

1

dephosphorylation

down-regulates activity

0.733

Upon ligand binding, IL-2R , IL-6R or LeptinR , IFN-_R , IFN-_R and PRLR or growth hormone (GH) receptor associated JAKs become activated. These JAKs mediate phosphorylation of specific tyrosine residues and recruit STATs. Activated STATs are released from the receptor and translocate to the nucleus. PTP1B dephosphorylates JAK2, TYK2 and STAT5 . The 45-kDa form of TC-PTP was shown to dephosphorylate JAK1 and JAK3 as well as STAT1, STAT3 and STAT5.

SIGNOR-133547

P00533

O60674

0

phosphorylation

up-regulates activity

0.612

Tyrosine at residue 1,068 of the EGFR is proposed to be one of the principal phosphorylation sites and Grb2-binding sites stimulated by growth hormone via Jak2. Our results indicate that the role of EGFR in signalling by growth hormone is to be phosphorylated by Jak2, thereby providing docking sites for Grb2 and activating MAP kinases and gene expression, independently of the intrinsic tyrosine kinase activity of EGFR.¬†

SIGNOR-251347

P84243

Q9NRC8

0

deacetylation

up-regulates activity

0.2

SIRT7 links H3K18 deacetylation to maintenance of oncogenic transformation.|Genome-wide binding studies reveal that SIRT7 binds to promoters of a specific set of gene targets, where it deacetylates H3K18Ac and promotes transcriptional repression.

SIGNOR-275872

P56945

Q14289

0

phosphorylation

up-regulates activity

0.782

Pyk2 knockdown also decreased p130Cas.|p130Cas and paxillin can be phosphorylated by Fak or Pyk2, and bind directly to these kinases.

SIGNOR-280100

Q9P2S2

Q9NZ94

2

binding

up-regulates activity

0.83

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

SIGNOR-264152

P24385

P35222

0

transcriptional regulation

up-regulates quantity by expression

0.801

One of the most well studied activators of CCND1 transcription is β-catenin, which could be actived by AKT signalling to inducing G1/S transition. When β-catenin is translocated from the cytoplasm to the nucleus, it forms a complex with the ternary complex factor (TCF) and/or lymphoid enhancer-binding factor (LEF) and stimulates cyclin D1 gene transcription (Fig. 4C).In agreement with the data described above, a chromatin immunoprecipitation (ChIP) assay confirmed that TNC regulates the binding of β-catenin to the TCF/LEF-binding site in the CCND1 promoter (Fig. 4C). Additionally, the β-cateninbinding activity with respect to the CCND1 promoter was much higher in TNC-overexpression PANC-1 cells than in the vector controls.

SIGNOR-277738

P02686

P09543

0

null

down-regulates activity

0.455

We provide evidence that CNP directly associates with and organizes the actin cytoskeleton, thereby providing an intracellular strut that counteracts membrane compaction by myelin basic protein (MBP).

SIGNOR-269269

P62942

P36897

2

binding

down-regulates activity

0.853

Blocking fkbp12/type i receptor interaction with fk506 nonfunctional derivatives enhances the ligand activity, indicating that fkbp12 binding is inhibitory to the signaling pathways of the tgf beta family ligands

SIGNOR-236142

Q13535

O14757

1

phosphorylation

up-regulates

0.925

Atr activation typically leads to chk1 phosphorylation and activation. In response to genotoxic stress, chk1 is phosphorylated on serines 317 (s317) and 345 (s345) by the ataxia-telangiectasia-related (atr) protein kinase.

SIGNOR-134716

Q92993

Q00987

0

polyubiquitination

down-regulates quantity by destabilization

0.654

Furthermore, we provide evidence that Mdm2, the ubiquitin ligase of the p53 tumour suppressor, interacts physically with Tip60 and induces its ubiquitylation and proteasome-dependent degradation.

SIGNOR-272613

Q6UXS9

P55211

1

cleavage

up-regulates

0.2

Caspase-12 specifically cleaves and activates procaspase-9 in cytosolic extracts. Results suggest that caspase-12 can activate caspase-9 without involvement of cytochromec.

SIGNOR-90318

Q7Z570

Q13489

1

transcriptional regulation

down-regulates quantity by repression

0.2

ZNF804A has been implicated in susceptibility to schizophrenia by several genome-wide association studies (GWAS), follow-up association studies and meta-analyses. ZNF804A was identified as a schizophrenia-associated gene by GWAS and was predicted to play a role in DNA binding and transcription To identify the genes that are affected by ZNF804A, we manipulated the expression of the ZNF804A protein in HEK293 human embryonic kidney cell lines and performed a cDNA microarray analysis followed by qPCR. We found that ZNF804A-overexpression up-regulated four genes (ANKRD1, INHBE, PIK3AP1, and DDIT3) and down-regulated three genes (CLIC2, MGAM, and BIRC3).

SIGNOR-269467

Q92934

P06493

0

phosphorylation

up-regulates activity

0.2

CDK1-mediated Bcl-2 serine 70 phosphorylation enhances its pro-apoptotic function, whereas CDK1-mediated Bad serine 128 phosphorylation promotes apoptosis.

SIGNOR-267921

Q13258

P38405

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-256898

O43557

Q92956

2

binding

up-regulates

0.857

A member of the tumor necrosis factor (tnf) superfamily, human tnfsf14 (htnfsf14)/hvem-l (herpes virus entry mediator ligand) was isolated as a cellular ligand for hvem/tr2 and human lymphotoxin beta receptor (ltbetar). Tnfsf14 induces apoptosis and suppresses tumor formation

SIGNOR-79328

Q12857

A6NFN3

1

transcriptional regulation

up-regulates quantity

0.261

For example, within the NFI targetome, we identified 6 collagen genes, 13 genes encoding potassium channel or glutamate receptor subunits and a range of factors related to axon guidance (e.g. Slit1, Robo1, Epha4, Epha5, Epha8)

SIGNOR-268911

P10451

P56178

0

transcriptional regulation

up-regulates quantity

0.373

Dlx5 initiates a complete osteogenic differentiation in these early primary cells, by triggering Runx2, osteopontin, alkaline phosphatase, and other gene expression according to the sequential temporal sequence observed during skull osteogenesis in vivo.

SIGNOR-245340

P17252

P52565

1

phosphorylation

down-regulates activity

0.449

PKCalpha phosphorylates RhoGDIalpha at Ser34 to reduce its affinity for RhoA (but not for Rac1 or Cdc42) .

SIGNOR-279097

O00187

P06681

1

cleavage

up-regulates activity

0.436

The MASPs in the preparations had proteolytic activities against C4, C2, and C3 in the fluid phase

SIGNOR-263416

Q12778

Q13043

0

phosphorylation

up-regulates

0.595

Bonni and coworkers demonstrated that mst1 can phosphorylate foxo3 (and subsequently, foxo1) principally ser207 (ser212 in foxo1), a conserved site in the forkhead domain. This phosphorylation interdicts 14-3-3 binding, promotes foxo nuclear residence and transcriptional activity. The other major signaling modules that directly regulate the activity of the foxo factors include the stress-activated jun-n-terminal kinase (jnk), the mammalian ortholog of the ste20-like protein kinase (mst1), and the deacetylase sirt1.

SIGNOR-191847

Q96RI1

P17252

0

phosphorylation

up-regulates

0.325

Phosphorylation of farnesoid x receptor by protein kinase c promotes its transcriptional activity. pkcalpha phosphorylates in vitro fxr in its dna-binding domain on s135 and s154.

SIGNOR-180537

Q96KB5

P12931

0

phosphorylation

up-regulates quantity by stabilization

0.395

Phosphorylation of TOPK at Y74, Y272 by Src increases the stability of TOPK and promotes tumorigenesis of colon

SIGNOR-277217

Q15139

O60602

1

phosphorylation

up-regulates

0.353

Pkd phosphorylated the tlr5-derived target peptide in vitro, and phosphorylation of the putative target serine 805 in hek 293t cell-derived tlr5 was identified by mass spectrometry. These results demonstrate that both pkd1 and pkd2 are required for inflammatory responses following tlr2, tlr4, or tlr5 activation, although pkd1 is more strongly involved

SIGNOR-154473

P28562

Q13950

1

dephosphorylation

up-regulates activity

0.353

In a separate study, MKP-1 was shown to induce osteogenesis by dephosphorylating Ser125 on Runx2 isoform type II (37).|MKP-1 increases RUNX2 activity and downregulates MAPK, cyclin D1 in differentiated osteoblasts inducing growth arrest and mineralization.

SIGNOR-277143

P68400

P11831

1

phosphorylation

up-regulates activity

0.552

Casein kinase II (CKII) phosphorylates the mammalian transcription factor serum response factor (SRF) on a serine residue(s) located within a region of the protein spanning amino acids 70 to 92, thereby enhancing its DNA-binding activity in vitro.| Nevertheless, additional mutation of serines 77 and 79 was required before phosphorylation and enhanced binding were completely abolished. Thus, serines 77 and 79 could also be recognized by CKII if serines 83 and 85 were mutated.

SIGNOR-250955

Q86XR7

O00206

2

binding

up-regulates

0.733

Mappit analysis of early toll-like receptor signalling events.

SIGNOR-160424

Q5S007

P46734

1

phosphorylation

up-regulates activity

0.393

LRRK2 phosphorylates MKK3 and MKK7 in vitro but has a relatively minor effect on MKK6 phosphorylation.

SIGNOR-279057

P51530

O96017

0

phosphorylation

up-regulates activity

0.526

We later observed that Dna2 phosphorylation by Cds1 is necessary for Dna2 association with chromatin in HU treated cells.

SIGNOR-279729

P33176

Q9NRI5

2

binding

up-regulates activity

0.2

We identified Kinesin-1, a microtubule-dependent and plus-end directed motor, as a DISC1-interacting molecule. Our results show that DISC1 links Kinesin-1 to the NUDEL/LIS1/14-3-3ε complex, serves as the cargo receptor, and regulates the transport of the complex to axons, leading to axon elongation. DISC1 directly interacted with kinesin heavy chain of Kinesin-1. Kinesin-1 interacted with the NUDEL/LIS1/14-3-3ε complex through DISC1

SIGNOR-252161

P08709

P38435

0

carboxylation

up-regulates activity

0.688

Thus, vitamin K acts as a cofactor for GGCX via the vitamin K cycle and exerts physiological effects through its regulation of VKDPs [29]. More than 20 VKDPs have been found. Osteocalcin promotes bone formation, and blood coagulation factors II, VII, IX, and X activate blood coagulation. Matrix Gla protein suppresses cardiovascular calcification, and brain-expressed Gas 6 promotes neural differentiation [29]. GGCX is an enzyme that converts glutamic acid (Glu) residues to Gla residues, so that the Gla-containing proteins can exert various physiological actions such as blood coagulation and bone formation.

SIGNOR-265919

Q99933

P11142

2

binding

up-regulates activity

0.895

Heat shock cognate protein 70 (Hsc70) regulates protein homeostasis through its reversible interactions with client proteins. Hsc70 has two major domains: a nucleotide-binding domain (NBD), that hydrolyzes ATP, and a substrate-binding domain (SBD), where clients are bound. Members of the BAG family of co-chaperones, including Bag1 and Bag3, are known to accelerate release of both ADP and client from Hsc70.

SIGNOR-254115

Q9Y478

Q92786

1

phosphorylation

down-regulates quantity by destabilization

0.2

Furthermore, the Ser79 phosphorylation of PROX1 by AMPK enhances the recruitment of CUL4-DDB1 ubiquitin ligase to promote PROX1 degradation.

SIGNOR-277609

Q9H334

Q9P283

1

transcriptional regulation

down-regulates quantity by repression

0.33

FoxP1 stimulates angiogenesis by repressing the inhibitory guidance protein semaphorin 5B in endothelial cells.

SIGNOR-269050