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
P20742	P08253	2	binding	down-regulates activity	0.329	Both PZP and a2M collagenase complexes incubated with gelatin demonstrated a significant inhibition of the catalytic activity\| MMP-2 and MMP-9 cause a significant degradation of these bands and the background, a degradation which is prevented by both a2M and PZP.	SIGNOR-261804
P53350	P40763	0	transcriptional regulation	up-regulates quantity by expression	0.306	Stat3 directly activated transcription of PLK1 in esophageal cancer cells and mouse embryonic fibroblast cell NIH3T3.	SIGNOR-271690
P22301	Q13651	2	binding	up-regulates	0.914	Functionally active il-10 receptors are composed of two distinct subunits. The il-10 receptor ? Chain is a 110-kda polypeptide that plays the dominant role in mediating high affinity ligand binding and signal transduction. The il-10 receptor ? Subunit (also known as crf2_4) is predicted to be a 40-kda polypeptide that is largely required only for signaling	SIGNOR-67964
P68400	Q9UHH9	1	phosphorylation	down-regulates quantity by destabilization	0.255	CK2 physiologically phosphorylates IP6K2 at amino acid residues S347 and S356 contained within a PEST sequence, a consensus site for ubiquitination. HCT116 cells depleted of IP6K2 are resistant to cell death elicited by CK2 inhibitors. CK2 phosphorylation at the degradation motif of IP6K2 enhances its ubiquitination and subsequent degradation.	SIGNOR-273625
Q99502	P16104	1	dephosphorylation	down-regulates	0.2	Tyr142 is dephosphorylated by the tyr phosphatases eya1 and eya3.	SIGNOR-168879
P15927	P49959	2	binding	up-regulates	0.2	The response to replication stress requires the recruitment of rpa and the mre11-rad50-nbs1 (mrn) complex.	SIGNOR-186648
Q99717	Q04771	0	phosphorylation	up-regulates	0.759	Bmp7 stimulated phosphorylation of endogenous smad1 and 5, formation of complexes with smad4 and induced the promoter for the homeobox gene, tlx2	SIGNOR-60171
P63096	O14842	2	binding	up-regulates activity	0.307	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-257071
Q06124	P04626	1	dephosphorylation	down-regulates	0.838	...which in turn suggests the importance SHP2 dephosphorylation of pTyr992 in EGFR and pTyr1023 in HER2 to mediate signaling.\|More specifically, we show that acidic residues N-terminal to the substrate pTyr in EGFR and HER2 mediate specific binding by the SHP2 active site, leading to blockade of RasGAP binding and optimal signaling by the two receptors.	SIGNOR-262957
P01106	Q96RU2	0	deubiquitination	up-regulates	0.703	Usp28, an ubiquitin-specific protease, binds to myc through an interaction with fbw7alpha, an f-box protein that is part of an scf-type ubiquitin ligase. Therefore, it stabilizes myc.	SIGNOR-155590
P00519	P46937	1	phosphorylation	up-regulates	0.718	In this study, we show that c-abl directly phosphorylates yap1 at position y357 in response to dna damage. Tyrosine-phosphorylated yap1 is a more stable protein that displays higher affinity to p73 and selectively coactivates p73 proapoptotic target genes.	SIGNOR-160860
O95837	P25116	2	binding	up-regulates activity	0.439	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-257293
Q08050	P06493	0	phosphorylation	up-regulates	0.762	A conserved phosphorylation site within the forkhead domain of foxm1b is required for its activation by cyclin-cdk1further analysis reveals that the leu-641 residue within an lxl motif is required for the recruitment of the cyclin-cdk complex, and the thr-596 residue is a critical cdk1 phosphorylation site within the activation domain of foxm1b. Cdk-dependent phosphorylation stimulates the foxm1b transcriptional activity	SIGNOR-187880
P29322	P52803	2	binding	up-regulates	0.819	Efna5 are able to activate epha8	SIGNOR-52479
P62136	O15169	1	dephosphorylation	down-regulates activity	0.333	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-248551
P07384	Q15078	1	cleavage	up-regulates activity	0.571	Calpains also modulate the activity of CDK5. Physiologically, CDK 5 is activated by p35 and its cleaved product p25. The latter has a longer half life than p35 and therefore it is a more potent activator of CDK5. The cleavage of p35 to p25 is mediated by calpain	SIGNOR-251583
Q13043	P31751	0	phosphorylation	down-regulates	0.262	Full activation of mst1 requires an activation cleavage that is prevented by the phosphorylation of thr-387 by akt.	SIGNOR-201125
P48736	P05771	0	phosphorylation	up-regulates activity	0.501	Remarkably we find that PKCβ phosphorylates Ser582 in the helical domain of the PI3Kγ catalytic subunit p110γ in response to clustering of the high-affinity IgE receptor (FcεRI) and/or store-operated Ca²⁺- influx in mast cells. Phosphorylation of p110γ correlates with the release of the p84 PI3Kγ adapter subunit from the p84-p110γ complex.As functional p84-p110γ is key to GPCR-mediated p110γ signaling, this suggests that PKCβ-mediated p110γ phosphorylation disconnects PI3Kγ from its canonical inputs from trimeric G proteins, and enables p110γ to operate downstream of Ca²⁺ and PKCβ.	SIGNOR-276496
P50391	P01298	2	binding	up-regulates	0.652	Human y4 bound human pp family members in i-pyy membrane binding assays with a distinctive rank order (table 1): pp > pyy > npy > npy free acid.	SIGNOR-24230
P04049	P98170	1	phosphorylation	up-regulates activity	0.504	Interaction and stabilization of X-linked inhibitor of apoptosis by Raf-1 protein kinase.\|We also demonstrate that Raf-1 phosphorylates XIAP in vitro and in vivo.	SIGNOR-279105
P56278	P31749	2	binding	up-regulates	0.478	Full-length tcl1 and its isoforms bind to akt / in in vitro kinase assays using gsk-3_ as a substrate, we found that the presence of any of the tcl1 family proteins (tcl1, mtcp1, or tcl1b) as gst fusion proteins significantly enhanced akt-induced gsk-3_ phosphorylation	SIGNOR-81671
P27361	P23467	0	dephosphorylation	up-regulates	0.432	When cells are stimulated with various ligands such as growth factors, hormones, neurotransmitters, or tumor promoters, erk1/2 is activated through dualphosphorylation at the -ptepy-motif. Subsequently, p-erk1/2 translocates into the nucleus and phosphorylates elk-1, thereby acting as a transcription factor for cell proliferationthese data indicate that sa-p-erk1/2 might not only be regulated by mkp such as rvhr, but also by pp1 and ptp as well	SIGNOR-103165
P25942	Q13114	2	binding	up-regulates activity	0.918	Cd40, a tumor necrosis factor receptor (tnfr) family member, forms a complex containing adaptor molecules traf2 and traf3.	SIGNOR-250560
P53350	Q3KR16	1	phosphorylation	up-regulates	0.415	We reported previously that a guanine nucleotide exchange factor, myogef, localizes to the central spindle, activates rhoa, and is required for cytokinesis. In this study, we have found that plk1 (polo-like kinase 1) can phosphorylate myogef, thereby recruiting myogef to the central spindle as well as enhancing myogef activity toward rhoa. The in vitro kinase assay shows that plk1 can phosphorylate myogef on threonine 574.	SIGNOR-179954
P05771	P21730	1	phosphorylation	down-regulates	0.2	Dynamics of protein kinase c-mediated phosphorylation of the complement c5a receptor on serine 334. Analysis of c5ar ser/ala mutants that possess a single intact serine residue either at position 334 or at neighboring positions 327, 332, or 338 revealed functional redundancy of c-terminal phosphorylation sites since all 4 serine residues could individually support c5ar internalization and desensitization	SIGNOR-151011
P01106	Q01196	0	transcriptional regulation	down-regulates quantity by repression	0.337	RUNX1 represses MYC expression through direct binding at three downstream enhancer elements	SIGNOR-260093
P0DPH8	Q5SQI0	0	acetylation	up-regulates quantity by stabilization	0.242	Alpha-Tubulin acetyltransferase (alphaTAT1) is the major α-tubulin lysine-40 (K40) acetyltransferase in mammals, nematodes, and protozoa, and its activity plays a conserved role in several microtubule-based processes.\|The tubulin subunits of microtubules are acetylated, and lysine-40 (K40) of the alpha-tubulin subunit has been identified as an important conserved site of microtubule acetylation (6–8). This modification is considered a hallmark of stable, long-lived microtubules	SIGNOR-272246
P00533	Q15645	2	phosphorylation	up-regulates quantity	0.2	Reciprocally, TRIP13 was phosphorylated at tyrosine(Y) 56 by EGFRvIII and EGF-activated EGFR. Abrogating TRIP13 Y56 phosphorylation dramatically attenuated TRIP13 expression-enhanced EGFR signaling and GBM cell growth.	SIGNOR-265083
Q99967	Q14119	0	transcriptional regulation	down-regulates quantity by repression	0.2	The transcription factor Vezf1 represses the expression of the antiangiogenic factor Cited2 in endothelial cells	SIGNOR-266883
P46531	Q8NES3	2	binding	up-regulates	0.757	We demonstrate that egf 12, a portion of the ligand-binding site, is modified with o-fucose and that this site is evolutionarily conserved. We also show that endogenous fringe proteins in chinese hamster ovary cells (lunatic fringe and radical fringe) as well as exogenous manic fringe modify o-fucose on many but not all egf repeats of mouse notch1.	SIGNOR-96537
Q13547	P19784	0	phosphorylation	up-regulates activity	0.398	Human HDAC1 protein was analyzed by ion trap mass spectrometry, and two phosphorylated serine residues, Ser(421) and Ser(423), were unambiguously identified. Loss of phosphorylation at Ser(421) and Ser(423) due to mutation to alanine or disruption of the casein kinase 2 consensus sequence directing phosphorylation reduced the enzymatic activity and complex formation of HDAC1.	SIGNOR-250999
P00519	Q14653	1	phosphorylation	up-regulates activity	0.2	The data in this study show that IRF3 is physically associated with c-Abl in vivo and directly binds to c-Abl in vitro. IRF3 is phosphorylated by c-Abl and c-Abl-related kinase, Arg, mainly at Y292.	SIGNOR-277440
O15194	P84022	1	dephosphorylation	up-regulates activity	0.424	Dephosphorylation of Smad2/3 Linkers by SCP2 and SCP3\|MAPK-mediated linker phosphorylation appears to have a dual role in Smad2/3 regulation. Mitogens and hyperactive Ras result in extracellular signal-regulated kinase (ERK)-mediated phosphorylation of Smad3 at Ser-204, Ser-208, and Thr-179 and of Smad2 at Ser-245/250/255 and Thr-220. Mutation of these sites increases the ability of Smad3 to activate target genes, suggesting that MAPK phosphorylation of Smad3 is inhibitory (11, 12). However, in contrast, ERK-dependent phosphorylation of Smad2 at Thr-8 enhances its transcriptional activity	SIGNOR-248306
P49918	Q16539	0	phosphorylation	up-regulates	0.262	G1-s control by p38/hog1 sapks upon osmostress. Upon osmostress, activated p38 and hog1 sapks phosphorylate the s/cdk inhibitor p57 or sic1 respectively at one single residue. In mammalian cells (left panel), p57 phosphorylation on thr143 leads to an increase of the affinity of p57 towards the cyclin a/cdk2 complex leading to a g1 arrest.	SIGNOR-198390
P12830	P12931	0	phosphorylation	down-regulates quantity by destabilization	0.755	Activated c-Src phosphorylated E-cadherin at the tyrosine 797 site to initiate RNF43-mediated E-cadherin ubiquitination at lysine 816 and subsequent degradation	SIGNOR-274048
Q99942	P49023	1	ubiquitination	down-regulates quantity	0.407	Here we demonstrate that the human homologue of RNF5 associates with the amino-terminal domain of paxillin, resulting in its ubiquitination. RNF5 requires intact RING and C-terminal domains to mediate paxillin ubiquitination. Concomitantly, RNF5 expression results in inhibition of cell motility. Via targeting of paxillin ubiquitination, which alters its localization, RNF5 emerges as a novel regulator of cell motility.	SIGNOR-271479
O15034	Q9UQ26	2	binding	down-regulates activity	0.531	SH3 domains of RBPs interact with RIMs. The enhancement of depolarization-induced secretion in PC12 cells by fusion proteins that suppress the associations of RBPs with RIMs and α1 suggests that RBPs may repress RIMs, either directly or through associated proteins.	SIGNOR-264366
P52757	Q05655	0	phosphorylation	down-regulates	0.269	A novel cross-talk in diacylglycerol signaling: the rac-gap beta2-chimaerin is negatively regulated by protein kinase cdelta-mediated phosphorylation. phosphorylation of beta2-chimaerin on ser(169) located in the sh2-c1 domain linker region via protein kinase cdelta, which retained beta2-chimaerin in the cytosol and prevented its c1 domain-mediated translocation to membranes	SIGNOR-164687
P49407	P27361	0	phosphorylation	down-regulates	0.716	Erk1 and erk2 phosphorylate beta-arrestin1 at ser-412 in vitro. . in the resting state, cytosolic arrestin1 proteins are constitutively phosphorylated by extracellular signal-regulated kinase (erk) at ser412, located within their distal c terminus. erk-phosphorylated arrestin1 is unable to associate with clathrin cages, whereas this constraint is removed upon its dephosphorylation	SIGNOR-67634
Q03431	P12272	2	binding	up-regulates activity	0.761	Prostate-specific antigen was found to specifically cleave PTHrP 1-141 in a time- and dose-dependent manner.\|The preferred PSA cleavage site of PTHrP 1-141 was determined to be at the carboxyl-terminus of phenylalanine 23, consistent with chymotryptic-like enzymatic activity of PSA. Cleavage of PTHrP by PSA completely abolished the ability of PTHrP to stimulate cAMP production.	SIGNOR-270549
O75369	Q96Q27	2	binding	down-regulates quantity by destabilization	0.416	Here, we provide the first evidence that a novel ASB2 isoform, ASB2beta, is important for muscle differentiation. ASB2beta is expressed in muscle cells during embryogenesis and in adult tissues. ASB2beta is part of an active E3 ubiquitin ligase complex and targets the actin-binding protein filamin B (FLNb) for proteasomal degradation. Altogether, our results indicated that ASB2β can assemble with elongin B, elongin C, Cullin 5 and Rbx2 to reconstitute an active E3 ubiquitin ligase complex.ASB2β induces polyubiquitylation of FLNb.	SIGNOR-271795
Q8ND25	P00533	0	phosphorylation	up-regulates activity	0.27	Together, these results demonstrate that EGFR-dependent phosphorylation of ZNRF1 at Y103 promotes degradation of AKT and resultant activation of GSK3\u03b2, which mediates oxidative stress\u2013induced neuronal apoptosis ( xref ).	SIGNOR-279522
O60825	P51812	0	phosphorylation	up-regulates activity	0.2	Heart 6-phosphofructo-2-kinase activation by insulin results from ser-466 and ser-483 phosphorylation and requires 3-phosphoinositide-dependent kinase-1, but not protein kinase b.	SIGNOR-23753
Q13535	P33991	1	phosphorylation	up-regulates	0.724	Together these data strongly support the conclusion that mec1 directly targets the s/tq sites in mcm4 and mcm6, although it is formally possible that mec1 and mrc1 activate a different s/tq-directed kinase to target mcm4 and mcm6.	SIGNOR-169412
Q9P0N8	P13569	1	ubiquitination	down-regulates quantity by destabilization	0.2	A catalytically dead MARCH2 RING mutant was unable to promote CFTR degradation.\|In vivo ubiquitination assays demonstrated the ubiquitination of CFTR by MARCH2, and overexpression of MARCH2, like that of CAL and STX6, led to a dose dependent degradation of mature CFTR that was blocked by bafilomycin A1 treatment.	SIGNOR-278584
P23677	P17612	0	phosphorylation	up-regulates activity	0.327	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-249994
P00352	O60678	2	binding	down-regulates activity	0.2	We identified the specific residues in the catalytic domain of PRMT3 that facilitate interaction with the C-terminal region of ALDH1A1. PRMT3 inhibits the enzymatic activity of ALDH1A1 and negatively regulates the expression of retinoic acid responsive genes in a methyltransferase activity independent manner.	SIGNOR-276751
O75385	O95166	2	binding	up-regulates	0.637	N-terminal proline/serine rich (ps) domain of ulk1 (amino acid 287-416) is required for ulk1-gate-16 and ulk1-gabarap protein interactions	SIGNOR-85614
P18846	Q13315	0	phosphorylation	up-regulates activity	0.359	Exposure to DNA damage further induced ATF1 phosphorylation on Ser-51 by ATM in a manner that required prior phosphorylation of the upstream CK residues.	SIGNOR-278909
O14640	P05412	2	binding	up-regulates	0.458	In this study, we discovered two novel interactions between dvl and c-jun and between dvl and beta-catenin in the nucleus that mediate the formation of a dvlc-junbeta-catenintcf functional complex.	SIGNOR-178038
P61586	Q9Y3M8	0	gtpase-activating protein	down-regulates activity	0.645	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-260521
Q9BYB0	P28482	0	phosphorylation	down-regulates activity	0.2	Interestingly, we discovered that several kinases in the MEK and ERK2 pathway destabilize Shank3 and that genetic deletion and pharmacological inhibition of ERK2 increases Shank3 abundance in vivo.\|We also determined that phosphorylation of Shank3 by ERK2 at selective residues promotes its ubiquitination and degradation.	SIGNOR-279538
O75581	P41221	2	binding	up-regulates activity	0.758	Wnt proteins bind to the frizzled receptors and lrp5/6 co-receptors, and through stabilizing the critical mediator betBeta-catenin, initiate a complex signaling cascade that plays an important role in regulating cell proliferation and differentiation.	SIGNOR-131841
O00206	Q86XR7	2	binding	up-regulates	0.733	Mappit analysis of early toll-like receptor signalling events.	SIGNOR-160424
O95630	O00238	0	phosphorylation	up-regulates activity	0.29	BMP type I receptor activation stimulates AMSH phosphorylation \| The exact position of phosphoserine residues in four phosphopeptides was identified by Edman degradation analysis; spot a for Ser243, Ser245 and Ser247, spot b for Ser2, and spots c and d for Ser48. To confirm the position of the phosphoserine residues, the serine residue(s) in each phosphopeptide was replaced by alanine residues. Then, each mutant as well as wild‐type AMSH was transfected into COS7 cells in the absence or presence of caALK6, and tryptic phosphopeptide mapping of each mutant was performed. As seen in Figure 7, each spot corresponding to the phosphopeptide containing phosphoserine disappeared in the tryptic phosphopeptide mapping. \| Thus, AMSH promotes BMP signaling by negatively regulating the function of I‐Smads.	SIGNOR-250600
O75676	O75676	2	phosphorylation	up-regulates activity	0.2	Here we report that the CK2 protein kinase, which contributes to NF-kappaB activation following UV radiation in a p38-dependent manner, physically interacts with MSK2 but not MSK1 and that CK2 inhibition specifically impairs UV-induced MSK2 kinase activation. A putative site of CK2 phosphorylation was mapped to MSK2 residue Ser(324) and when substituted to alanine (S324A) also compromised MSK2 activity.Serine 324 is required for UV-induced MSK2 activation and for autophosphorylation at MSK2-Ser196.	SIGNOR-276269
O15534	P04150	0	transcriptional regulation	up-regulates quantity by expression	0.268	GR directly regulates transcription of circadian clock components in mouse and human primary MSCs. Per2, E4bp4, Per1, and Timeless rapidly respond to glucocorticoid stimulation. Primary glucocorticoid receptor (GR) target genes are those at which GR occupies a nearby genomic glucocorticoid response element (GRE) and regulates target gene transcription	SIGNOR-268050
Q9BX66	P22681	2	binding	up-regulates	0.688	Cbl is recruited to the insulin receptor by interaction with the adapter protein cap, through one of three adjacent sh3 domains in the carboxy terminus of cap	SIGNOR-82283
P68400	Q13563	1	phosphorylation	up-regulates	0.421	Ser(812) can be phosphorylated by ck2 in vitro and substitution s812a results in failure to incorporate phosphate in cultured epithelial cells.	SIGNOR-121572
Q92953	Q9P0L0	1	relocalization	up-regulates quantity	0.2	Confirmation that Kv2.1 and -2.2 bind VAPA and VAPB employed colocalization/redistribution, siRNA knockdown, and Förster resonance energy transfer (FRET)-based assays.\|As Kv2.1 accumulates on the surface it begins to bind ER VAPs and form the large and stable membrane junctions.	SIGNOR-262124
P05771	P06400	1	phosphorylation	down-regulates activity	0.352	The exact mechanism by which PKCbeta degrades RB is unknown.\|To attribute increased RB phosphorylation specifically to PKC\u03b2, we transiently transfected PKC\u03b2 -/- hepatocytes, and reintroduction of PKC\u03b2 specifically resulted in increased in phospho-RB (Ser780) levels, further supporting that PKC\u03b2 phosphorylates RB specifically at Ser780 without affecting phosphorylation at other residues (Ser807 and Ser811) (Figure xref ).	SIGNOR-280083
P10636-4	Q96L34	0	phosphorylation	down-regulates activity	0.419	AMPK phosphorylation inhibits tau binding of microtubules. In order to study further the phosphorylation of tau by AMPK, we compared phosphorylation of tau by MARK4 or AMPK using a panel of phospho-tau antibodies (Figure 2A). Five phosphorylation sites common to both kinases were identified (Thr231, Ser262, Ser356, Ser396 and Ser422). In addition, AMPK, but not MARK4, was capable of phosphorylating Ser214 (Figure 2A).	SIGNOR-273934
P51812	Q13315	1	phosphorylation	up-regulates activity	0.388	Furthermore, using RSK2 knockout mouse fibroblasts and RSK2 deficient cells from CLS patients, we demonstrate that ablation of RSK2 impairs the phosphorylation of Atm at Ser1981 and the phosphorylation of p53 at Ser18 (mouse) or Ser15 (human) in response to genotoxic stress.\|We postulate that the phosphorylation of RSK2 is required to fully activate Atm at Ser1981 and p53 at Ser18 (mouse) or Ser15 (human) in response to genotoxic stress.	SIGNOR-280118
Q13882	Q13882	2	phosphorylation	up-regulates	0.2	Autophosphorylation increases enzyme activity of wild-type brk but not of a y342a mutant form of brk.	SIGNOR-90604
Q08209	Q14934	1	dephosphorylation	up-regulates	0.566	Calcineurin directly dephosphorylates nfat resulting in the nuclear import of nfat.	SIGNOR-176379
Q05655	P49841	1	phosphorylation	down-regulates activity	0.271	In the TFEB activation pathway, activated PKC\u03b4 phosphorylates and inactivates GSK3\u03b2, leading to the reduced phosphorylation of TFEB at Ser134 and Ser138 residues; this reduced phosphorylation is critical for the cytoplasmic sequestration of TFEB.\|In the TFEB activation pathway, activated PKCdelta phosphorylates and inactivates GSK3beta, leading to the reduced phosphorylation of TFEB at Ser134 and Ser138 residues; this reduced phosphorylation is critical for the cytoplasmic sequestration of TFEB.	SIGNOR-280084
Q13153	P78545	1	phosphorylation	up-regulates	0.456	Phosphorylation-dependent regulation of stability and transforming potential of ets transcriptional factor ese-1 by p21-activated kinase 1. Pak1 selectively phosphorylates ese-1 at ser(207). Intriguingly, pak1 phosphorylation inactive mutant ese1-s207a is more unstable	SIGNOR-154743
P35222	Q13634	2	binding	up-regulates activity	0.576	At its C-terminus, cadherin interacts with Î²-catenin, which dynamically associates with Î±-catenin, a direct binding partner of filamentous actin	SIGNOR-265857
Q96FW1	P68400	0	phosphorylation	up-regulates activity	0.319	Casein kinase 2 (CK2)-dependent phosphorylation of OTUB1 at Ser16 played a critical role in ODN- and cathepsin K siRNA-mediated p53 stabilization. \|Furthermore, although OTUB1 dramatically induced p53 deubiquitination, its mutant (S16A) and deletion mutant did not have this effec	SIGNOR-276527
O00327	P31751	0	phosphorylation	down-regulates activity	0.358	Consistent with mass spectrometry results, constitutive active Akt2 (Akt2-CA) induced wild-type (WT) Bmal1 protein phosphorylation, which was abolished by a serine to alanine mutation at Ser42 residue (S42A) but not a S422A/S513A double mutation, as shown by immunoblot assay with phospho-Akt substrate antiserum ( xref ).\|In line with the in vivo results, overexpression of Akt2-CA strikingly lowered Bmal1 protein abundance in the nucleus in primary hepatocytes (XREF_FIG and XREF_SUPPLEMENTARY).	SIGNOR-280177
P16333	P22681	0	ubiquitination	down-regulates quantity by destabilization	0.644	Taken together, these results show that lysine 178 in Nck1 is the acceptor site for ubiquitin transferred by c-Cbl, and that the ubiquitination of Nck1 by c-Cbl is blocked in the presence of synaptopodin.	SIGNOR-278606
P35236	P28482	2	dephosphorylation	down-regulates activity	0.812	HePTP efficiently dephosphorylated active ERK2 on the tyrosine residue in the activation loop in vitro. Together, these data identify ERK2 as a specific and direct target of HePTP and are consistent with a model in which HePTP negatively regulates ERK2 activity as part of a feedback mechanism	SIGNOR-248484
Q15424	P35637	1	relocalization	up-regulates activity	0.363	SAFB1 as well as Matrin3 to regulate splicing and ligand-mediated transcription\| In addition, depletion of SAFB1 reduced FUS's localization to chromatin-bound fraction and splicing activity, suggesting SAFB1 could tether FUS to chromatin compartment thorough N-terminal DNA-binding motif.	SIGNOR-262821
P00533	Q9ULV8	0	polyubiquitination	down-regulates quantity by destabilization	0.761	In summary, we have shown that CBLC and AIP4 can interact and that these two E3 ligases could contribute to down-regulate EGFR signaling by ubiquitination.	SIGNOR-272605
P15172	P38936	1	transcriptional regulation	up-regulates	0.4	P21 is regulated by MyoD and myogenin in normal muscle cells and the inactivation of these factors in RMS cells contributes to the silencing of p21 in RMS cells	SIGNOR-251574
Q9UPY8	O14965	0	phosphorylation	up-regulates	0.442	Aurora-a and aurora-b phosphorylate eb3 at ser-176 in a spatial and cell cycle-specific manner, respectively during mitosis two kinases, aurora-a and aurora-b, phosphorylate eb3 at ser-176, and the resulting phosphorylation disrupts the eb3-siah-1 complex. Indeed, eb3 is stabilized during mitosis and facilitates cell cycle progression.	SIGNOR-187657
Q07817	Q13323	2	binding	down-regulates	0.808	We have identified a novel cellular protein, bik, that interacts with the cellular survival-promoting proteins, bcl-2 and bcl-xl in transient transfection assays, bik promotes cell death in a manner similar to the death-promoting members of the bcl-2 family, bax and bak.	SIGNOR-26453
P49815	O00141	0	phosphorylation	down-regulates activity	0.579	SGK1, which is activated by PDK1, contributes to the maintenance of residual mTORC1 activity through direct phosphorylation and inhibition of TSC2.	SIGNOR-277266
Q14669	Q13564	1	ubiquitination	down-regulates quantity by destabilization	0.432	Our data suggest that that TRIP12 promotes degradation of APP-BP1 by catalyzing its ubiquitination, which in turn modulates the neddylation pathway.	SIGNOR-266780
Q8N4N8	P53350	0	phosphorylation	up-regulates activity	0.66	We show that Plk1 directly phosphorylates Kif2b at threonine 125 (T125) and serine 204 (S204), and that these two sites differentially regulate Kif2b function. Phosphorylation of S204 is required for the kinetochore localization and activity of Kif2b in prometaphase, and phosphorylation of T125 is required for Kif2b activity in the correction of k-MT attachment errors.	SIGNOR-252049
P25021	P63092	2	binding	up-regulates activity	0.454	Here we systematically quantified ligand-induced interactions between 148 GPCRs and all 11 unique G alpha subunit C-termini. For each receptor, we probed chimeric G alpha subunit activation via a transforming growth factor-alpha (TGF alpha) shedding response in HEK293 cells lacking endogenous Gq/11- and G12/13- signaling. \| We defined positive coupling if any member of the subfamily scored LogRAi ‚â• -1 and negative coupling if all of the members scored LogRAi < -1 (Figure 3A-B). ROC analysis gives AUC = 0.78 (Figure S4A) when considering high-confidence known coupling data and suggested a threshold of LogRAi ‚â• -1.0 for defining true couplings. \| The score associated to this interaction has a LogRAi ‚â• -1.0.	SIGNOR-256777
P55771	Q9UGL1	2	binding	up-regulates activity	0.483	Human PLU-1 Has transcriptional repression properties and interacts with the developmental transcription factors BF-1 and PAX9. In a reporter assay system, PLU-1 has potent transcriptional repression activity. BF-1 and PAX9 also represses transcription in the same assay, but co-expression of PLU-1 with BF-1 or PAX9 significantly enhances this repression	SIGNOR-223875
P32239	P01350	2	binding	up-regulates	0.783	A segment of five amino acids in the second extracellular loop of the cck-b receptor was shown to be essential for the high affinity of the natural peptide agonits, gastrin,	SIGNOR-66987
P10589	Q8TAB3	1	transcriptional regulation	up-regulates quantity by expression	0.2	We demonstrated that high expression of COUP-TFI induces MEC cell fate and protocadherin 19 expression. We next demonstrated that COUP-TFI is able to directly bind to a conserved Sp1/COUP-TFI binding site in the Pcdh19 promoter region by chromatin immunoprecipitation (ChIP) (Fig. 6, E and F).	SIGNOR-267223
P24941	Q8IZL9	0	phosphorylation	up-regulates	0.387	P42 is essential for the phosphorylation of thr-160 and activation of cdk2.	SIGNOR-118986
Q9UHD9	Q00839	2	binding	up-regulates quantity by stabilization	0.333	Confirmation of binding of recombinant full-length hnRNPA1 and hnRNPU proteins with ubiquilin-2 by GST-pull-down assays\|Additionally, our evidence that ubiquilin-2 is in- volved in stabilizing hnRNPA1 protein	SIGNOR-262271
Q02952	Q13535	0	phosphorylation	up-regulates activity	0.2	The expression of either ATR-KD or the addition of the ATR kinase inhibitor VE-821 to ATR-WT expressing cells caused AKAP12 to be retained within the cytoplasm.\|With UV damage, ATR phosphorylates AKAP12 at S732 which stimulates nuclear translocation of an AKAP12\u2013ATR-pS435 complex that results in enhanced 5\u2032 strand incision of NER.	SIGNOR-278292
Q01196	Q03014	1	transcriptional regulation	up-regulates quantity	0.271	We identified Hhex as a direct target of RUNX1 and FLT3-ITD stimulation and confirmed high HHEX expression in FLT3-ITD AMLs. HHEX could replace RUNX1 in cooperating with FLT3-ITD to induce AML.	SIGNOR-256305
Q14103	P49841	0	phosphorylation	down-regulates activity	0.346	In kinase assays pka phosphorylated ser-87 of hnrnp d, whereas glycogen synthase kinase-3 beta (gsk-3 beta) phosphorylated ser-83, but only if ser-87 had been pre-phosphorylated by pka. Phosphorylation of ser-87 enhanced, whereas phosphorylation of ser-83 repressed, transactivation.	SIGNOR-102582
P25205	P24941	0	phosphorylation	up-regulates	0.796	In this study, we demonstrate that mcm3 is a substrate of cyclin e/cdk2 and can be phosphorylated by cyclin e/cdk2 at thr-722.	SIGNOR-176656
P54253	O75582	0	phosphorylation	up-regulates quantity by stabilization	0.26	In summary, the data from the cell based screen, biochemical studies and genetic interactions strongly suggest that MSK1 phosphorylates ATXN1 and regulates its stability.	SIGNOR-279109
P78527	P54619	1	phosphorylation	up-regulates activity	0.2	PRKDC interacted with the AMPK complex and phosphorylated its nucleotide-sensing γ1 subunit PRKAG1/AMPKγ1 at Ser192 and Thr284, both events being significantly reduced upon the activation of the AMPK complex. Alanine substitutions of PRKDC phosphorylation sites in PRKAG1 reduced AMPK complex activation without affecting its nucleotide sensing capacity.	SIGNOR-277503
P04637	P50750	0	phosphorylation	up-regulates	0.535	We recently demonstrated that through their physical interaction, cdk9 phosphorylates p53 on ser-392, leading to p53 stability and accumulation	SIGNOR-201935
P53350	O43663	1	phosphorylation	down-regulates activity	0.723	Plk1 negatively regulates PRC1 to prevent premature midzone formation before cytokinesis.\|Plk1, but not Cdk1, phosphorylates PRC1 on Thr-602 to prevent premature midzone assembly in metaphase.	SIGNOR-279645
Q9Y625	P41221	2	binding	down-regulates activity	0.374	GPC6 binds to Wnt5a and inhibits its release from producing cells. Based on theseresults, and in our finding that GPC6 inhibits non-canonical Wnt signaling in the developing intestine,we tested the hypothesis that GPC6 binds to Wnt5aat the surface of the Wnt5a-producing mesenchymalcells and restrains its release from them.	SIGNOR-264030
P08709	P00734	0	null	up-regulates activity	0.301	Thrombin also activates the cofactors FVIII (to FVIIIa) and FV (to FVa) and activates platelets such that they provide a procoagulant membrane surface to which these proteins then bind	SIGNOR-263529
Q99590	P49768	1	cleavage	up-regulates activity	0.294	Remarkably, the caspases acting on PS1 could be subdivided in two groups. One group, containing caspase-8, -6 and -11, cleaved PS1 after residues ENDD329 and to a lesser extent after residues AQRD341. A second group consisting of caspase-3, -7 and -1 acted uniquely on AQRD341. Importantly, these two cleavage sites were also recognized by caspases in the C-terminal PS1 fragment produced by constitutive proteolysis.	SIGNOR-261758
P78552	P35225	2	binding	up-regulates	0.853	It is now known that this alternate receptor is a heterodimer, the type ii il-4 receptor or the il-13 receptor, which is comprised of IL-4R And IL-13R1.	SIGNOR-100750
Q14563	Q9HCM2	2	binding	up-regulates activity	0.763	We provide evidence suggesting that, in endothelial cells and glioblastoma cells, plexin-A4 is a required component of both Sema3A and Sema3B receptor complexes and inhibition of its expression nullifies both Sema3A and Sema3B signaling. The specificity for Sema3A or Sema3B is determined by the presence of plexin-A1 in Sema3A receptors and plexin-A2 in Sema3B receptors, and silencing each abrogates signaling by the appropriate semaphorin.	SIGNOR-261811
Q6NZ36	P49841	0	phosphorylation	down-regulates quantity	0.2	Furthermore, GSK3beta was able to decrease the cellular FAAP20 levels when overexpressed in wild-type, but not in FBW7 -/- HCT116 cells, indicating that GSK3beta requires downstream FBW7 to regulate the FAAP20 stability.\|GSK3\u03b2 phosphorylates FAAP20 at Ser113.	SIGNOR-279048

P20742

P08253

2

binding

down-regulates activity

0.329

Both PZP and a2M collagenase complexes incubated with gelatin demonstrated a significant inhibition of the catalytic activity| MMP-2 and MMP-9 cause a significant degradation of these bands and the background, a degradation which is prevented by both a2M and PZP.

SIGNOR-261804

P53350

P40763

0

transcriptional regulation

up-regulates quantity by expression

0.306

Stat3 directly activated transcription of PLK1 in esophageal cancer cells and mouse embryonic fibroblast cell NIH3T3.

SIGNOR-271690

P22301

Q13651

2

binding

up-regulates

0.914

Functionally active il-10 receptors are composed of two distinct subunits. The il-10 receptor ? Chain is a 110-kda polypeptide that plays the dominant role in mediating high affinity ligand binding and signal transduction. The il-10 receptor ? Subunit (also known as crf2_4) is predicted to be a 40-kda polypeptide that is largely required only for signaling

SIGNOR-67964

P68400

Q9UHH9

1

phosphorylation

down-regulates quantity by destabilization

0.255

CK2 physiologically phosphorylates IP6K2 at amino acid residues S347 and S356 contained within a PEST sequence, a consensus site for ubiquitination. HCT116 cells depleted of IP6K2 are resistant to cell death elicited by CK2 inhibitors. CK2 phosphorylation at the degradation motif of IP6K2 enhances its ubiquitination and subsequent degradation.

SIGNOR-273625

Q99502

P16104

1

dephosphorylation

down-regulates

0.2

Tyr142 is dephosphorylated by the tyr phosphatases eya1 and eya3.

SIGNOR-168879

P15927

P49959

2

binding

up-regulates

0.2

The response to replication stress requires the recruitment of rpa and the mre11-rad50-nbs1 (mrn) complex.

SIGNOR-186648

Q99717

Q04771

0

phosphorylation

up-regulates

0.759

Bmp7 stimulated phosphorylation of endogenous smad1 and 5, formation of complexes with smad4 and induced the promoter for the homeobox gene, tlx2

SIGNOR-60171

P63096

O14842

2

binding

up-regulates activity

0.307

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-257071

Q06124

P04626

1

dephosphorylation

down-regulates

0.838

...which in turn suggests the importance SHP2 dephosphorylation of pTyr992 in EGFR and pTyr1023 in HER2 to mediate signaling.|More specifically, we show that acidic residues N-terminal to the substrate pTyr in EGFR and HER2 mediate specific binding by the SHP2 active site, leading to blockade of RasGAP binding and optimal signaling by the two receptors.

SIGNOR-262957

P01106

Q96RU2

0

deubiquitination

up-regulates

0.703

Usp28, an ubiquitin-specific protease, binds to myc through an interaction with fbw7alpha, an f-box protein that is part of an scf-type ubiquitin ligase. Therefore, it stabilizes myc.

SIGNOR-155590

P00519

P46937

1

phosphorylation

up-regulates

0.718

In this study, we show that c-abl directly phosphorylates yap1 at position y357 in response to dna damage. Tyrosine-phosphorylated yap1 is a more stable protein that displays higher affinity to p73 and selectively coactivates p73 proapoptotic target genes.

SIGNOR-160860

O95837

P25116

2

binding

up-regulates activity

0.439

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-257293

Q08050

P06493

0

phosphorylation

up-regulates

0.762

A conserved phosphorylation site within the forkhead domain of foxm1b is required for its activation by cyclin-cdk1further analysis reveals that the leu-641 residue within an lxl motif is required for the recruitment of the cyclin-cdk complex, and the thr-596 residue is a critical cdk1 phosphorylation site within the activation domain of foxm1b. Cdk-dependent phosphorylation stimulates the foxm1b transcriptional activity

SIGNOR-187880

P29322

P52803

2

binding

up-regulates

0.819

Efna5 are able to activate epha8

SIGNOR-52479

P62136

O15169

1

dephosphorylation

down-regulates activity

0.333

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-248551

P07384

Q15078

1

cleavage

up-regulates activity

0.571

Calpains also modulate the activity of CDK5. Physiologically, CDK 5 is activated by p35 and its cleaved product p25. The latter has a longer half life than p35 and therefore it is a more potent activator of CDK5. The cleavage of p35 to p25 is mediated by calpain

SIGNOR-251583

Q13043

P31751

0

phosphorylation

down-regulates

0.262

Full activation of mst1 requires an activation cleavage that is prevented by the phosphorylation of thr-387 by akt.

SIGNOR-201125

P48736

P05771

0

phosphorylation

up-regulates activity

0.501

Remarkably we find that PKCβ phosphorylates Ser582 in the helical domain of the PI3Kγ catalytic subunit p110γ in response to clustering of the high-affinity IgE receptor (FcεRI) and/or store-operated Ca²⁺- influx in mast cells. Phosphorylation of p110γ correlates with the release of the p84 PI3Kγ adapter subunit from the p84-p110γ complex.As functional p84-p110γ is key to GPCR-mediated p110γ signaling, this suggests that PKCβ-mediated p110γ phosphorylation disconnects PI3Kγ from its canonical inputs from trimeric G proteins, and enables p110γ to operate downstream of Ca²⁺ and PKCβ.

SIGNOR-276496

P50391

P01298

2

binding

up-regulates

0.652

Human y4 bound human pp family members in i-pyy membrane binding assays with a distinctive rank order (table 1): pp > pyy > npy > npy free acid.

SIGNOR-24230

P04049

P98170

1

phosphorylation

up-regulates activity

0.504

Interaction and stabilization of X-linked inhibitor of apoptosis by Raf-1 protein kinase.|We also demonstrate that Raf-1 phosphorylates XIAP in vitro and in vivo.

SIGNOR-279105

P56278

P31749

2

binding

up-regulates

0.478

Full-length tcl1 and its isoforms bind to akt / in in vitro kinase assays using gsk-3_ as a substrate, we found that the presence of any of the tcl1 family proteins (tcl1, mtcp1, or tcl1b) as gst fusion proteins significantly enhanced akt-induced gsk-3_ phosphorylation

SIGNOR-81671

P27361

P23467

0

dephosphorylation

up-regulates

0.432

When cells are stimulated with various ligands such as growth factors, hormones, neurotransmitters, or tumor promoters, erk1/2 is activated through dualphosphorylation at the -ptepy-motif. Subsequently, p-erk1/2 translocates into the nucleus and phosphorylates elk-1, thereby acting as a transcription factor for cell proliferationthese data indicate that sa-p-erk1/2 might not only be regulated by mkp such as rvhr, but also by pp1 and ptp as well

SIGNOR-103165

P25942

Q13114

2

binding

up-regulates activity

0.918

Cd40, a tumor necrosis factor receptor (tnfr) family member, forms a complex containing adaptor molecules traf2 and traf3.

SIGNOR-250560

P53350

Q3KR16

1

phosphorylation

up-regulates

0.415

We reported previously that a guanine nucleotide exchange factor, myogef, localizes to the central spindle, activates rhoa, and is required for cytokinesis. In this study, we have found that plk1 (polo-like kinase 1) can phosphorylate myogef, thereby recruiting myogef to the central spindle as well as enhancing myogef activity toward rhoa. The in vitro kinase assay shows that plk1 can phosphorylate myogef on threonine 574.

SIGNOR-179954

P05771

P21730

1

phosphorylation

down-regulates

0.2

Dynamics of protein kinase c-mediated phosphorylation of the complement c5a receptor on serine 334. Analysis of c5ar ser/ala mutants that possess a single intact serine residue either at position 334 or at neighboring positions 327, 332, or 338 revealed functional redundancy of c-terminal phosphorylation sites since all 4 serine residues could individually support c5ar internalization and desensitization

SIGNOR-151011

P01106

Q01196

0

transcriptional regulation

down-regulates quantity by repression

0.337

RUNX1 represses MYC expression through direct binding at three downstream enhancer elements

SIGNOR-260093

P0DPH8

Q5SQI0

0

acetylation

up-regulates quantity by stabilization

0.242

Alpha-Tubulin acetyltransferase (alphaTAT1) is the major α-tubulin lysine-40 (K40) acetyltransferase in mammals, nematodes, and protozoa, and its activity plays a conserved role in several microtubule-based processes.|The tubulin subunits of microtubules are acetylated, and lysine-40 (K40) of the alpha-tubulin subunit has been identified as an important conserved site of microtubule acetylation (6–8). This modification is considered a hallmark of stable, long-lived microtubules

SIGNOR-272246

P00533

Q15645

2

phosphorylation

up-regulates quantity

0.2

Reciprocally, TRIP13 was phosphorylated at tyrosine(Y) 56 by EGFRvIII and EGF-activated EGFR. Abrogating TRIP13 Y56 phosphorylation dramatically attenuated TRIP13 expression-enhanced EGFR signaling and GBM cell growth.

SIGNOR-265083

Q99967

Q14119

0

transcriptional regulation

down-regulates quantity by repression

0.2

The transcription factor Vezf1 represses the expression of the antiangiogenic factor Cited2 in endothelial cells

SIGNOR-266883

P46531

Q8NES3

2

binding

up-regulates

0.757

We demonstrate that egf 12, a portion of the ligand-binding site, is modified with o-fucose and that this site is evolutionarily conserved. We also show that endogenous fringe proteins in chinese hamster ovary cells (lunatic fringe and radical fringe) as well as exogenous manic fringe modify o-fucose on many but not all egf repeats of mouse notch1.

SIGNOR-96537

Q13547

P19784

0

phosphorylation

up-regulates activity

0.398

Human HDAC1 protein was analyzed by ion trap mass spectrometry, and two phosphorylated serine residues, Ser(421) and Ser(423), were unambiguously identified. Loss of phosphorylation at Ser(421) and Ser(423) due to mutation to alanine or disruption of the casein kinase 2 consensus sequence directing phosphorylation reduced the enzymatic activity and complex formation of HDAC1.

SIGNOR-250999

P00519

Q14653

1

phosphorylation

up-regulates activity

0.2

The data in this study show that IRF3 is physically associated with c-Abl in vivo and directly binds to c-Abl in vitro. IRF3 is phosphorylated by c-Abl and c-Abl-related kinase, Arg, mainly at Y292.

SIGNOR-277440

O15194

P84022

1

dephosphorylation

up-regulates activity

0.424

Dephosphorylation of Smad2/3 Linkers by SCP2 and SCP3|MAPK-mediated linker phosphorylation appears to have a dual role in Smad2/3 regulation. Mitogens and hyperactive Ras result in extracellular signal-regulated kinase (ERK)-mediated phosphorylation of Smad3 at Ser-204, Ser-208, and Thr-179 and of Smad2 at Ser-245/250/255 and Thr-220. Mutation of these sites increases the ability of Smad3 to activate target genes, suggesting that MAPK phosphorylation of Smad3 is inhibitory (11, 12). However, in contrast, ERK-dependent phosphorylation of Smad2 at Thr-8 enhances its transcriptional activity

SIGNOR-248306

P49918

Q16539

0

phosphorylation

up-regulates

0.262

G1-s control by p38/hog1 sapks upon osmostress. Upon osmostress, activated p38 and hog1 sapks phosphorylate the s/cdk inhibitor p57 or sic1 respectively at one single residue. In mammalian cells (left panel), p57 phosphorylation on thr143 leads to an increase of the affinity of p57 towards the cyclin a/cdk2 complex leading to a g1 arrest.

SIGNOR-198390

P12830

P12931

0

phosphorylation

down-regulates quantity by destabilization

0.755

Activated c-Src phosphorylated E-cadherin at the tyrosine 797 site to initiate RNF43-mediated E-cadherin ubiquitination at lysine 816 and subsequent degradation

SIGNOR-274048

Q99942

P49023

1

ubiquitination

down-regulates quantity

0.407

Here we demonstrate that the human homologue of RNF5 associates with the amino-terminal domain of paxillin, resulting in its ubiquitination. RNF5 requires intact RING and C-terminal domains to mediate paxillin ubiquitination. Concomitantly, RNF5 expression results in inhibition of cell motility. Via targeting of paxillin ubiquitination, which alters its localization, RNF5 emerges as a novel regulator of cell motility.

SIGNOR-271479

O15034

Q9UQ26

2

binding

down-regulates activity

0.531

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

SIGNOR-264366

P52757

Q05655

0

phosphorylation

down-regulates

0.269

A novel cross-talk in diacylglycerol signaling: the rac-gap beta2-chimaerin is negatively regulated by protein kinase cdelta-mediated phosphorylation. phosphorylation of beta2-chimaerin on ser(169) located in the sh2-c1 domain linker region via protein kinase cdelta, which retained beta2-chimaerin in the cytosol and prevented its c1 domain-mediated translocation to membranes

SIGNOR-164687

P49407

P27361

0

phosphorylation

down-regulates

0.716

Erk1 and erk2 phosphorylate beta-arrestin1 at ser-412 in vitro. . in the resting state, cytosolic arrestin1 proteins are constitutively phosphorylated by extracellular signal-regulated kinase (erk) at ser412, located within their distal c terminus. erk-phosphorylated arrestin1 is unable to associate with clathrin cages, whereas this constraint is removed upon its dephosphorylation

SIGNOR-67634

Q03431

P12272

2

binding

up-regulates activity

0.761

Prostate-specific antigen was found to specifically cleave PTHrP 1-141 in a time- and dose-dependent manner.|The preferred PSA cleavage site of PTHrP 1-141 was determined to be at the carboxyl-terminus of phenylalanine 23, consistent with chymotryptic-like enzymatic activity of PSA. Cleavage of PTHrP by PSA completely abolished the ability of PTHrP to stimulate cAMP production.

SIGNOR-270549

O75369

Q96Q27

2

binding

down-regulates quantity by destabilization

0.416

Here, we provide the first evidence that a novel ASB2 isoform, ASB2beta, is important for muscle differentiation. ASB2beta is expressed in muscle cells during embryogenesis and in adult tissues. ASB2beta is part of an active E3 ubiquitin ligase complex and targets the actin-binding protein filamin B (FLNb) for proteasomal degradation. Altogether, our results indicated that ASB2β can assemble with elongin B, elongin C, Cullin 5 and Rbx2 to reconstitute an active E3 ubiquitin ligase complex.ASB2β induces polyubiquitylation of FLNb.

SIGNOR-271795

Q8ND25

P00533

0

phosphorylation

up-regulates activity

0.27

Together, these results demonstrate that EGFR-dependent phosphorylation of ZNRF1 at Y103 promotes degradation of AKT and resultant activation of GSK3\u03b2, which mediates oxidative stress\u2013induced neuronal apoptosis ( xref ).

SIGNOR-279522

O60825

P51812

0

phosphorylation

up-regulates activity

0.2

Heart 6-phosphofructo-2-kinase activation by insulin results from ser-466 and ser-483 phosphorylation and requires 3-phosphoinositide-dependent kinase-1, but not protein kinase b.

SIGNOR-23753

Q13535

P33991

1

phosphorylation

up-regulates

0.724

Together these data strongly support the conclusion that mec1 directly targets the s/tq sites in mcm4 and mcm6, although it is formally possible that mec1 and mrc1 activate a different s/tq-directed kinase to target mcm4 and mcm6.

SIGNOR-169412

Q9P0N8

P13569

1

ubiquitination

down-regulates quantity by destabilization

0.2

A catalytically dead MARCH2 RING mutant was unable to promote CFTR degradation.|In vivo ubiquitination assays demonstrated the ubiquitination of CFTR by MARCH2, and overexpression of MARCH2, like that of CAL and STX6, led to a dose dependent degradation of mature CFTR that was blocked by bafilomycin A1 treatment.

SIGNOR-278584

P23677

P17612

0

phosphorylation

up-regulates activity

0.327

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-249994

P00352

O60678

2

binding

down-regulates activity

0.2

We identified the specific residues in the catalytic domain of PRMT3 that facilitate interaction with the C-terminal region of ALDH1A1. PRMT3 inhibits the enzymatic activity of ALDH1A1 and negatively regulates the expression of retinoic acid responsive genes in a methyltransferase activity independent manner.

SIGNOR-276751

O75385

O95166

2

binding

up-regulates

0.637

N-terminal proline/serine rich (ps) domain of ulk1 (amino acid 287-416) is required for ulk1-gate-16 and ulk1-gabarap protein interactions

SIGNOR-85614

P18846

Q13315

0

phosphorylation

up-regulates activity

0.359

Exposure to DNA damage further induced ATF1 phosphorylation on Ser-51 by ATM in a manner that required prior phosphorylation of the upstream CK residues.

SIGNOR-278909

O14640

P05412

2

binding

up-regulates

0.458

In this study, we discovered two novel interactions between dvl and c-jun and between dvl and beta-catenin in the nucleus that mediate the formation of a dvlc-junbeta-catenintcf functional complex.

SIGNOR-178038

P61586

Q9Y3M8

0

gtpase-activating protein

down-regulates activity

0.645

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-260521

Q9BYB0

P28482

0

phosphorylation

down-regulates activity

0.2

Interestingly, we discovered that several kinases in the MEK and ERK2 pathway destabilize Shank3 and that genetic deletion and pharmacological inhibition of ERK2 increases Shank3 abundance in vivo.|We also determined that phosphorylation of Shank3 by ERK2 at selective residues promotes its ubiquitination and degradation.

SIGNOR-279538

O75581

P41221

2

binding

up-regulates activity

0.758

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

SIGNOR-131841

O00206

Q86XR7

2

binding

up-regulates

0.733

Mappit analysis of early toll-like receptor signalling events.

SIGNOR-160424

O95630

O00238

0

phosphorylation

up-regulates activity

0.29

BMP type I receptor activation stimulates AMSH phosphorylation | The exact position of phosphoserine residues in four phosphopeptides was identified by Edman degradation analysis; spot a for Ser243, Ser245 and Ser247, spot b for Ser2, and spots c and d for Ser48. To confirm the position of the phosphoserine residues, the serine residue(s) in each phosphopeptide was replaced by alanine residues. Then, each mutant as well as wild‐type AMSH was transfected into COS7 cells in the absence or presence of caALK6, and tryptic phosphopeptide mapping of each mutant was performed. As seen in Figure 7, each spot corresponding to the phosphopeptide containing phosphoserine disappeared in the tryptic phosphopeptide mapping. | Thus, AMSH promotes BMP signaling by negatively regulating the function of I‐Smads.

SIGNOR-250600

O75676

2

phosphorylation

up-regulates activity

0.2

Here we report that the CK2 protein kinase, which contributes to NF-kappaB activation following UV radiation in a p38-dependent manner, physically interacts with MSK2 but not MSK1 and that CK2 inhibition specifically impairs UV-induced MSK2 kinase activation. A putative site of CK2 phosphorylation was mapped to MSK2 residue Ser(324) and when substituted to alanine (S324A) also compromised MSK2 activity.Serine 324 is required for UV-induced MSK2 activation and for autophosphorylation at MSK2-Ser196.

SIGNOR-276269

O15534

P04150

0

transcriptional regulation

up-regulates quantity by expression

0.268

GR directly regulates transcription of circadian clock components in mouse and human primary MSCs. Per2, E4bp4, Per1, and Timeless rapidly respond to glucocorticoid stimulation. Primary glucocorticoid receptor (GR) target genes are those at which GR occupies a nearby genomic glucocorticoid response element (GRE) and regulates target gene transcription

SIGNOR-268050

Q9BX66

P22681

2

binding

up-regulates

0.688

Cbl is recruited to the insulin receptor by interaction with the adapter protein cap, through one of three adjacent sh3 domains in the carboxy terminus of cap

SIGNOR-82283

P68400

Q13563

1

phosphorylation

up-regulates

0.421

Ser(812) can be phosphorylated by ck2 in vitro and substitution s812a results in failure to incorporate phosphate in cultured epithelial cells.

SIGNOR-121572

Q92953

Q9P0L0

1

relocalization

up-regulates quantity

0.2

Confirmation that Kv2.1 and -2.2 bind VAPA and VAPB employed colocalization/redistribution, siRNA knockdown, and Förster resonance energy transfer (FRET)-based assays.|As Kv2.1 accumulates on the surface it begins to bind ER VAPs and form the large and stable membrane junctions.

SIGNOR-262124

P05771

P06400

1

phosphorylation

down-regulates activity

0.352

The exact mechanism by which PKCbeta degrades RB is unknown.|To attribute increased RB phosphorylation specifically to PKC\u03b2, we transiently transfected PKC\u03b2 -/- hepatocytes, and reintroduction of PKC\u03b2 specifically resulted in increased in phospho-RB (Ser780) levels, further supporting that PKC\u03b2 phosphorylates RB specifically at Ser780 without affecting phosphorylation at other residues (Ser807 and Ser811) (Figure xref ).

SIGNOR-280083

P10636-4

Q96L34

0

phosphorylation

down-regulates activity

0.419

AMPK phosphorylation inhibits tau binding of microtubules. In order to study further the phosphorylation of tau by AMPK, we compared phosphorylation of tau by MARK4 or AMPK using a panel of phospho-tau antibodies (Figure 2A). Five phosphorylation sites common to both kinases were identified (Thr231, Ser262, Ser356, Ser396 and Ser422). In addition, AMPK, but not MARK4, was capable of phosphorylating Ser214 (Figure 2A).

SIGNOR-273934

P51812

Q13315

1

phosphorylation

up-regulates activity

0.388

Furthermore, using RSK2 knockout mouse fibroblasts and RSK2 deficient cells from CLS patients, we demonstrate that ablation of RSK2 impairs the phosphorylation of Atm at Ser1981 and the phosphorylation of p53 at Ser18 (mouse) or Ser15 (human) in response to genotoxic stress.|We postulate that the phosphorylation of RSK2 is required to fully activate Atm at Ser1981 and p53 at Ser18 (mouse) or Ser15 (human) in response to genotoxic stress.

SIGNOR-280118

Q13882

2

phosphorylation

up-regulates

0.2

Autophosphorylation increases enzyme activity of wild-type brk but not of a y342a mutant form of brk.

SIGNOR-90604

Q08209

Q14934

1

dephosphorylation

up-regulates

0.566

Calcineurin directly dephosphorylates nfat resulting in the nuclear import of nfat.

SIGNOR-176379

Q05655

P49841

1

phosphorylation

down-regulates activity

0.271

In the TFEB activation pathway, activated PKC\u03b4 phosphorylates and inactivates GSK3\u03b2, leading to the reduced phosphorylation of TFEB at Ser134 and Ser138 residues; this reduced phosphorylation is critical for the cytoplasmic sequestration of TFEB.|In the TFEB activation pathway, activated PKCdelta phosphorylates and inactivates GSK3beta, leading to the reduced phosphorylation of TFEB at Ser134 and Ser138 residues; this reduced phosphorylation is critical for the cytoplasmic sequestration of TFEB.

SIGNOR-280084

Q13153

P78545

1

phosphorylation

up-regulates

0.456

Phosphorylation-dependent regulation of stability and transforming potential of ets transcriptional factor ese-1 by p21-activated kinase 1. Pak1 selectively phosphorylates ese-1 at ser(207). Intriguingly, pak1 phosphorylation inactive mutant ese1-s207a is more unstable

SIGNOR-154743

P35222

Q13634

2

binding

up-regulates activity

0.576

At its C-terminus, cadherin interacts with Î²-catenin, which dynamically associates with Î±-catenin, a direct binding partner of filamentous actin

SIGNOR-265857

Q96FW1

P68400

0

phosphorylation

up-regulates activity

0.319

Casein kinase 2 (CK2)-dependent phosphorylation of OTUB1 at Ser16 played a critical role in ODN- and cathepsin K siRNA-mediated p53 stabilization. |Furthermore, although OTUB1 dramatically induced p53 deubiquitination, its mutant (S16A) and deletion mutant did not have this effec

SIGNOR-276527

O00327

P31751

0

phosphorylation

down-regulates activity

0.358

Consistent with mass spectrometry results, constitutive active Akt2 (Akt2-CA) induced wild-type (WT) Bmal1 protein phosphorylation, which was abolished by a serine to alanine mutation at Ser42 residue (S42A) but not a S422A/S513A double mutation, as shown by immunoblot assay with phospho-Akt substrate antiserum ( xref ).|In line with the in vivo results, overexpression of Akt2-CA strikingly lowered Bmal1 protein abundance in the nucleus in primary hepatocytes (XREF_FIG and XREF_SUPPLEMENTARY).

SIGNOR-280177

P16333

P22681

0

ubiquitination

down-regulates quantity by destabilization

0.644

Taken together, these results show that lysine 178 in Nck1 is the acceptor site for ubiquitin transferred by c-Cbl, and that the ubiquitination of Nck1 by c-Cbl is blocked in the presence of synaptopodin.

SIGNOR-278606

P35236

P28482

2

dephosphorylation

down-regulates activity

0.812

HePTP efficiently dephosphorylated active ERK2 on the tyrosine residue in the activation loop in vitro. Together, these data identify ERK2 as a specific and direct target of HePTP and are consistent with a model in which HePTP negatively regulates ERK2 activity as part of a feedback mechanism

SIGNOR-248484

Q15424

P35637

1

relocalization

up-regulates activity

0.363

SAFB1 as well as Matrin3 to regulate splicing and ligand-mediated transcription| In addition, depletion of SAFB1 reduced FUS's localization to chromatin-bound fraction and splicing activity, suggesting SAFB1 could tether FUS to chromatin compartment thorough N-terminal DNA-binding motif.

SIGNOR-262821

P00533

Q9ULV8

0

polyubiquitination

down-regulates quantity by destabilization

0.761

In summary, we have shown that CBLC and AIP4 can interact and that these two E3 ligases could contribute to down-regulate EGFR signaling by ubiquitination.

SIGNOR-272605

P15172

P38936

1

transcriptional regulation

up-regulates

0.4

P21 is regulated by MyoD and myogenin in normal muscle cells and the inactivation of these factors in RMS cells contributes to the silencing of p21 in RMS cells

SIGNOR-251574

Q9UPY8

O14965

0

phosphorylation

up-regulates

0.442

Aurora-a and aurora-b phosphorylate eb3 at ser-176 in a spatial and cell cycle-specific manner, respectively during mitosis two kinases, aurora-a and aurora-b, phosphorylate eb3 at ser-176, and the resulting phosphorylation disrupts the eb3-siah-1 complex. Indeed, eb3 is stabilized during mitosis and facilitates cell cycle progression.

SIGNOR-187657

Q07817

Q13323

2

binding

down-regulates

0.808

We have identified a novel cellular protein, bik, that interacts with the cellular survival-promoting proteins, bcl-2 and bcl-xl in transient transfection assays, bik promotes cell death in a manner similar to the death-promoting members of the bcl-2 family, bax and bak.

SIGNOR-26453

P49815

O00141

0

phosphorylation

down-regulates activity

0.579

SGK1, which is activated by PDK1, contributes to the maintenance of residual mTORC1 activity through direct phosphorylation and inhibition of TSC2.

SIGNOR-277266

Q14669

Q13564

1

ubiquitination

down-regulates quantity by destabilization

0.432

Our data suggest that that TRIP12 promotes degradation of APP-BP1 by catalyzing its ubiquitination, which in turn modulates the neddylation pathway.

SIGNOR-266780

Q8N4N8

P53350

0

phosphorylation

up-regulates activity

0.66

We show that Plk1 directly phosphorylates Kif2b at threonine 125 (T125) and serine 204 (S204), and that these two sites differentially regulate Kif2b function. Phosphorylation of S204 is required for the kinetochore localization and activity of Kif2b in prometaphase, and phosphorylation of T125 is required for Kif2b activity in the correction of k-MT attachment errors.

SIGNOR-252049

P25021

P63092

2

binding

up-regulates activity

0.454

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

SIGNOR-256777

P55771

Q9UGL1

2

binding

up-regulates activity

0.483

Human PLU-1 Has transcriptional repression properties and interacts with the developmental transcription factors BF-1 and PAX9. In a reporter assay system, PLU-1 has potent transcriptional repression activity. BF-1 and PAX9 also represses transcription in the same assay, but co-expression of PLU-1 with BF-1 or PAX9 significantly enhances this repression

SIGNOR-223875

P32239

P01350

2

binding

up-regulates

0.783

A segment of five amino acids in the second extracellular loop of the cck-b receptor was shown to be essential for the high affinity of the natural peptide agonits, gastrin,

SIGNOR-66987

P10589

Q8TAB3

1

transcriptional regulation

up-regulates quantity by expression

0.2

We demonstrated that high expression of COUP-TFI induces MEC cell fate and protocadherin 19 expression. We next demonstrated that COUP-TFI is able to directly bind to a conserved Sp1/COUP-TFI binding site in the Pcdh19 promoter region by chromatin immunoprecipitation (ChIP) (Fig. 6, E and F).

SIGNOR-267223

P24941

Q8IZL9

0

phosphorylation

up-regulates

0.387

P42 is essential for the phosphorylation of thr-160 and activation of cdk2.

SIGNOR-118986

Q9UHD9

Q00839

2

binding

up-regulates quantity by stabilization

0.333

Confirmation of binding of recombinant full-length hnRNPA1 and hnRNPU proteins with ubiquilin-2 by GST-pull-down assays|Additionally, our evidence that ubiquilin-2 is in- volved in stabilizing hnRNPA1 protein

SIGNOR-262271

Q02952

Q13535

0

phosphorylation

up-regulates activity

0.2

The expression of either ATR-KD or the addition of the ATR kinase inhibitor VE-821 to ATR-WT expressing cells caused AKAP12 to be retained within the cytoplasm.|With UV damage, ATR phosphorylates AKAP12 at S732 which stimulates nuclear translocation of an AKAP12\u2013ATR-pS435 complex that results in enhanced 5\u2032 strand incision of NER.

SIGNOR-278292

Q01196

Q03014

1

transcriptional regulation

up-regulates quantity

0.271

We identified Hhex as a direct target of RUNX1 and FLT3-ITD stimulation and confirmed high HHEX expression in FLT3-ITD AMLs. HHEX could replace RUNX1 in cooperating with FLT3-ITD to induce AML.

SIGNOR-256305

Q14103

P49841

0

phosphorylation

down-regulates activity

0.346

In kinase assays pka phosphorylated ser-87 of hnrnp d, whereas glycogen synthase kinase-3 beta (gsk-3 beta) phosphorylated ser-83, but only if ser-87 had been pre-phosphorylated by pka. Phosphorylation of ser-87 enhanced, whereas phosphorylation of ser-83 repressed, transactivation.

SIGNOR-102582

P25205

P24941

0

phosphorylation

up-regulates

0.796

In this study, we demonstrate that mcm3 is a substrate of cyclin e/cdk2 and can be phosphorylated by cyclin e/cdk2 at thr-722.

SIGNOR-176656

P54253

O75582

0

phosphorylation

up-regulates quantity by stabilization

0.26

In summary, the data from the cell based screen, biochemical studies and genetic interactions strongly suggest that MSK1 phosphorylates ATXN1 and regulates its stability.

SIGNOR-279109

P78527

P54619

1

phosphorylation

up-regulates activity

0.2

PRKDC interacted with the AMPK complex and phosphorylated its nucleotide-sensing γ1 subunit PRKAG1/AMPKγ1 at Ser192 and Thr284, both events being significantly reduced upon the activation of the AMPK complex. Alanine substitutions of PRKDC phosphorylation sites in PRKAG1 reduced AMPK complex activation without affecting its nucleotide sensing capacity.

SIGNOR-277503

P04637

P50750

0

phosphorylation

up-regulates

0.535

We recently demonstrated that through their physical interaction, cdk9 phosphorylates p53 on ser-392, leading to p53 stability and accumulation

SIGNOR-201935

P53350

O43663

1

phosphorylation

down-regulates activity

0.723

Plk1 negatively regulates PRC1 to prevent premature midzone formation before cytokinesis.|Plk1, but not Cdk1, phosphorylates PRC1 on Thr-602 to prevent premature midzone assembly in metaphase.

SIGNOR-279645

Q9Y625

P41221

2

binding

down-regulates activity

0.374

GPC6 binds to Wnt5a and inhibits its release from producing cells. Based on theseresults, and in our finding that GPC6 inhibits non-canonical Wnt signaling in the developing intestine,we tested the hypothesis that GPC6 binds to Wnt5aat the surface of the Wnt5a-producing mesenchymalcells and restrains its release from them.

SIGNOR-264030

P08709

P00734

0

null

up-regulates activity

0.301

Thrombin also activates the cofactors FVIII (to FVIIIa) and FV (to FVa) and activates platelets such that they provide a procoagulant membrane surface to which these proteins then bind

SIGNOR-263529

Q99590

P49768

1

cleavage

up-regulates activity

0.294

Remarkably, the caspases acting on PS1 could be subdivided in two groups. One group, containing caspase-8, -6 and -11, cleaved PS1 after residues ENDD329 and to a lesser extent after residues AQRD341. A second group consisting of caspase-3, -7 and -1 acted uniquely on AQRD341. Importantly, these two cleavage sites were also recognized by caspases in the C-terminal PS1 fragment produced by constitutive proteolysis.

SIGNOR-261758

P78552

P35225

2

binding

up-regulates

0.853

It is now known that this alternate receptor is a heterodimer, the type ii il-4 receptor or the il-13 receptor, which is comprised of IL-4R And IL-13R1.

SIGNOR-100750

Q14563

Q9HCM2

2

binding

up-regulates activity

0.763

We provide evidence suggesting that, in endothelial cells and glioblastoma cells, plexin-A4 is a required component of both Sema3A and Sema3B receptor complexes and inhibition of its expression nullifies both Sema3A and Sema3B signaling. The specificity for Sema3A or Sema3B is determined by the presence of plexin-A1 in Sema3A receptors and plexin-A2 in Sema3B receptors, and silencing each abrogates signaling by the appropriate semaphorin.

SIGNOR-261811

Q6NZ36

P49841

0

phosphorylation

down-regulates quantity

0.2

Furthermore, GSK3beta was able to decrease the cellular FAAP20 levels when overexpressed in wild-type, but not in FBW7 -/- HCT116 cells, indicating that GSK3beta requires downstream FBW7 to regulate the FAAP20 stability.|GSK3\u03b2 phosphorylates FAAP20 at Ser113.

SIGNOR-279048