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
Q2M1Z3	P49841	0	phosphorylation	up-regulates activity	0.302	We show that GSK-3alpha and -beta interact with CdGAP in mammalian cells. We also demonstrate that GSK-3 phosphorylates CdGAP both in vitro and in vivo on Thr-776, which we have previously shown to be an ERK 1/2 phosphorylation site involved in CdGAP regulation.	SIGNOR-262879
P35612	P17612	0	phosphorylation	down-regulates activity	0.283	Ser-726 and Ser-713 in the C-terminal MARCKS-related domains of - and -adducin, respectively, were identified as the major phosphorylation sites common for PKA and PKC. Phosphorylation by PKA, but not PKC, reduced the affinity of adducin for spectrin-F-actin complexes as well as the activity of adducin in promoting binding of spectrin to F-actin.	SIGNOR-250332
Q92769	P19784	0	phosphorylation	up-regulates activity	0.39	HDAC2 is phosphorylated uniquely by protein kinase CK2 in vitro. Studies using unfractionated cell extracts with CK2 inhibitors suggest that protein kinase CK2 is the major source of HDAC2 kinase. Finally, and perhaps most interesting, HDAC2 phosphorylation promotes enzymatic activity, selectively regulates complex formation, but has no effect on transcriptional repression. \| Since our data suggest that protein kinase CK2 is the major kinase responsible for HDAC2 phosphorylation, and because Ser422 and Ser424, but not Ser411, lie within CK2 recognition sequences, we believe that Ser394, Ser422, and Ser424 constitute the three phosphorylated residues in HDAC2.	SIGNOR-251001
P17612	Q16891	1	phosphorylation	down-regulates activity	0.2	PKA directly phosphorylated the Ser528 residue of MIC60. Phosphorylation of MIC60 Interrupts Parkin Recruitment and Formation of the MICOS Complex	SIGNOR-266302
Q96EP0	P29466	2	polyubiquitination	up-regulates activity	0.2	HOIP forms a constitutive interaction with caspase-1 and mediates the linear ubiquitination of the CARD pro-domain. Upon engagement of apoptosis, caspase-1 and caspase-8 cleave HOIP at Asp-348 and Asp-387, limiting the ability of LUBAC to ubiquitinate substrates.	SIGNOR-272191
P12931	P19174	1	phosphorylation	up-regulates activity	0.636	The phosphorylation of purified phospholipase C-gamma 1 (PLC-gamma 1) and PLC-gamma 2 by src-family-protein tyrosine kinases (PTKs) P56lck, p53/56lyn, p59hck, p59fyn, and p60src was studied in vitro. All five PTKs phosphorylated PLC-gamma 1 and PLC-gamma 2, suggesting that both PLC-gamma isozymes can be phosphorylated in cells by any of the src-family PTKs in response to the activation of cell surface receptors.	SIGNOR-247316
O14983	P16157	2	binding	down-regulates activity	0.293	We recently reported that small ankyrin 1 (sAnk1) interacts with the sarco(endo)plasmic reticulum Ca2+-ATPase in skeletal muscle (SERCA1) to inhibit its activity.	SIGNOR-265927
P19086	Q96RI0	2	binding	up-regulates activity	0.2	Here we systematically quantified ligand-induced interactions between 148 GPCRs and all 11 unique G alpha subunit C-termini. For each receptor, we probed chimeric G alpha subunit activation via a transforming growth factor-alpha (TGF alpha) shedding response in HEK293 cells lacking endogenous Gq/11- and G12/13- signaling. \| We defined positive coupling if any member of the subfamily scored LogRAi ≥ -1 and negative coupling if all of the members scored LogRAi < -1 (Figure 3A-B). ROC analysis gives AUC = 0.78 (Figure S4A) when considering high-confidence known coupling data and suggested a threshold of LogRAi ≥ -1.0 for defining true couplings. \| The score associated to this interaction has a LogRAi ≥ -1.0.	SIGNOR-257312
P14598	P28482	0	phosphorylation	up-regulates	0.45	Erk1/2 are the kinases involved in p47phox_ phosphorylation on ser345 in gm-csfprimed human neutrophils._ Phosphorylation of ser345 is required for the priming of nadph oxidase activity in neutrophil-like cells	SIGNOR-147170
P42261	Q15818	2	binding	up-regulates activity	0.296	We found that NP1 colocalizes and physically associates with the fast excitatory GluR1 AMPA receptors and that hypoxia induces a time-dependent increase in the NP1-GluR1 interactions. Thus hypoxia recruits NP1 protein to GluR1 subunits concurrent with the hypoxic excitotoxic cascade.\|Rather we propose that through interactions with GluR1 clusters, NP1 modulates the function of AMPA receptors in a manner whereby increased NP1-GluR1 interactions sensitize neurons to hypoxia-induced excitotoxic death.	SIGNOR-261430
P12931	O14578	1	phosphorylation	up-regulates activity	0.273	CitK is tyrosine phosphorylated by Src in response to EphB2 signaling.	SIGNOR-279484
P0DP24	P16298	2	binding	up-regulates	0.511	Calcium-bound calmodulin associates with calcineurin (cn), releasing the phosphatase from the repressive effects on an autoinhibitory domain.	SIGNOR-266322
P12757	Q13485	2	binding	down-regulates activity	0.886	Thus, SnoN can interact with Smad4 and Smad2 and inhibit their abilities to activate transcription.	SIGNOR-71633
Q13639	P63096	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-257041
Q8IUC6	O00206	2	binding	up-regulates activity	0.85	To initiate the innate immune response, Toll-like receptors (TLRs) associate with cytoplasmic adaptor proteins through TIR (Toll/interleukin-1 receptor) domain interactions. The four principal signaling adaptor proteins include MyD88, MAL, TRIF and TRAM, and the fifth protein SARM, involved in negative regulation of TLR pathways, is usually considered a part of the TIR domain-containing adaptor protein group	SIGNOR-252067
P31749	Q15121	1	phosphorylation	up-regulates activity	0.517	Protein kinase b/akt binds and phosphorylates ped/pea-15, stabilizing its antiapoptotic action.	SIGNOR-102092
P67775	Q9Y570	0	demethylation	down-regulates activity	0.905	Methylation of the carboxy-terminal Leu309 in a conserved TPDYFL309 motif of the C subunit has been shown to enhance the affinity of the PP2A core enzyme for some, but not all, regulatory subunits \|Demethylation and negative regulation of PP2A is mediated by a PP2A-specific methylesterase PME-1, which is conserved from yeast to humans.	SIGNOR-265748
Q96RJ3	Q9Y275	2	binding	up-regulates activity	0.785	Baff specifically binds baff receptor	SIGNOR-135713
P43629	P68400	0	phosphorylation	up-regulates quantity by stabilization	0.2	Functional studies of the wild-type receptor and serine/threonine mutants indicated that phosphorylation of Ser(394) by protein kinase C slightly suppresses KIR3DL1 inhibitory function, and reduces receptor internalization and turnover.Both CKII and PKC phosphorylate KIR3DL1 in vitro. Ser364 can be phosphorylated after phosphorylation of Ser367 by CKII. It seems that phosphorylation of 3DL1 by CK does not significantly affect receptor inhibitory function or turnover, at least in the assays that we have used so far.	SIGNOR-276077
O00744	Q9NPG1	2	binding	up-regulates	0.617	Wnt proteins bind to the frizzled receptors and lrp5/6 co-receptors, and through stabilizing the critical mediator betBeta-catenin, initiate a complex signaling cascade that plays an important role in regulating cell proliferation and differentiation.	SIGNOR-131625
Q13315	Q13315	2	phosphorylation	up-regulates activity	0.2	In human cells, the activation process involves autophosphorylation on three sites (ser367, ser1893, and ser1981) and acetylation on lys3016. We now describe the identification of a new atm phosphorylation site, thr(p)1885 and an additional autophosphorylation site, ser(p)2996, that is highly dna damage-inducible.	SIGNOR-170477
P53350	Q12834	1	phosphorylation	down-regulates quantity by destabilization	0.977	Plk1 directly bound to Cdc20 and phosphorylates it on serine-170 located in CRY-box. Whereas wild-type Cdc20 was degraded according to progress cell cycle beyond mitosis, the phosphorylation-defective mutant, which serine-170 was changed into alanine, was not destroyed in early G1 phase.	SIGNOR-276493
P08069	Q92569	2	binding	up-regulates	0.807	Moreover, we found that the insulin-like growth factor-1 receptor (igf-ir) bound to p55pik;the interaction occurred at the receptor tyrosine 1316 and involved both p55pik sh2 domains.	SIGNOR-52683
P56524	Q96GD4	0	phosphorylation	down-regulates	0.264	We define the precise site of aurb-mediated phosphorylation as a conserved serine within the nuclear localization signals of hdac4, hdac5, and hdac9 at ser265, ser278, and ser242, respectivelyduring mitosis, aurb-mediated phosphorylation may localize class iia hdacs to a phosphorylation gradient at the spindle midzone, permitting temporal and spatial regulatory mechanisms altering hdac protein interactions	SIGNOR-198646
Q08999	Q92878	2	binding	up-regulates activity	0.304	We propose that p130, forming a complex with Rad50 through RINT-1, blocks telomerase-independent telomere lengthening in normal cells.	SIGNOR-265029
Q13976	P78347	1	phosphorylation	up-regulates	0.569	G-kinase phosphorylated tfii-i in vitro and in vivo on ser(371) and ser(743) outside of the interaction domain. G-kinase strongly enhanced tfii-i transactivation of a serum-response element-containing promoter in cos7 cells	SIGNOR-89849
P17252	P29353	1	phosphorylation	up-regulates activity	0.401	Among them, Ser(29) in p52(Shc) (equivalent to Ser(138) in p66(Shc)) was phosphorylated only after TPA stimulation. Phosphorylation of this site together with the intact phosphotyrosine-binding domain was essential for ShcA binding to the protein-tyrosine phosphatase PTP-PEST. TPA-induced ShcA phosphorylation at this site (and hence, its association with PTP-PEST) was inhibited by a protein kinase C-specific inhibitor and was induced by overexpression of constitutively active mutants of protein kinase Calpha, -epsilon, and -delta isoforms.	SIGNOR-249150
O95239	O14965	0	phosphorylation	up-regulates activity	0.419	We show that Aurora A phosphorylates the condensin I-dependent pool of KIF4A and thus actively promotes chromosome congression from the spindle poles to the metaphase plate. In vitro kinase assays showed that recombinant KIF4A can be phosphorylated by Aurora A and that this activity is inhibited by the specific Aurora A inhibitor MLN8537 (Fig. 7 C).	SIGNOR-265993
P43405	Q13261	1	phosphorylation	up-regulates activity	0.329	Mutation of a defined region of the intracellular signaling portion of IL-15Ralpha (Tyr227) abrogates both the IL-15Ralpha/Syk association and IL-15Ralpha phosphorylation. Taken together, this suggests that Syk kinase physically and functionally associates with the IL-15Ralpha chain in B cells and that Syk plays a key role in mediating IL-15-induced signal transduction, thus accounting for the distinct functional consequences of IL-15 vs IL-2 binding to B cells	SIGNOR-246556
Q8N6F7	P62993	2	binding	down-regulates activity	0.2	Herein, we demonstrate that the adaptor protein HGAL, specifically expressed in GC lymphocytes and GC-derived lymphomas, directly binds to Grb2 upon BCR activation and negates the inhibitory effects of Grb2 on the BCR-induced biochemical signaling cascade.	SIGNOR-273608
P30304	P49137	0	phosphorylation	down-regulates	0.364	Mk2 was required for the degradation of cdc25a. Mk2 phosphorylates cdc25a in vitro. Phosphorylation of cdc25a in vivo has been shown to facilitate its ubiquitin-mediated proteolysis	SIGNOR-152996
Q58F21	P62805	0	relocalization	up-regulates activity	0.2	BRDT interacts with acetylated nucleosomes via its BD1 domain. Binding may be initiated through non-specific interactions with DNA, which allow BRDT to localize to chromatin. Specificity is generated through recognition of tandem acetylated lysine residues (K5ac/K8ac) on the histone H4 tail,	SIGNOR-262066
O00139	Q6IQ55	0	phosphorylation	down-regulates activity	0.406	TTBK2 phosphorylates KIF2A primarily at growing MT ends and counteracts the depolymerization activity of KIF2A	SIGNOR-260926
Q15911	Q14258	0	polyubiquitination	down-regulates quantity by destabilization	0.451	In the present study we show that EFP (oestrogen-responsive finger protein) is an E3 ubiquitin ligase mediating oestrogen-induced ATBF1 protein degradation. Knockdown of EFP increases ATBF1 protein levels, whereas overexpression of EFP decreases ATBF1 protein levels.	SIGNOR-272048
Q5XX13	P04406	1	polyubiquitination	up-regulates activity	0.2	Mechanistically, FBXW10 promotes GAPDH polyubiquitination and activation; VRK2-dependent phosphorylation of GAPDH Ser151 residue is critical for GAPDH ubiquitination and activation.	SIGNOR-277841
P27361	Q02548	1	phosphorylation	down-regulates activity	0.247	In this study, we demonstrated that PAX5 was phosphorylated by ERK1/2 in vitro and in vivo at serines 189 and 283. This phosphorylation attenuated the transcriptional repression of BLIMP1 by PAX5.	SIGNOR-269086
Q14524	Q13557	0	phosphorylation	down-regulates	0.492	A stable interaction between ?(C)-camkii and the intracellular loop between domains 1 and 2 of na(v)1.5 was observed. This region was also phosphorylated by ?(C)-camkii, specifically at the ser-516 and thr-594 sites.Wild-type (wt) and phosphomutant hna(v)1.5 were co-expressed with gfp-?(C)-camkii in hek293 cells, and i(na) was recorded. As observed in myocytes, camkii shifted wt i(na) availability to a more negative membrane potential and enhanced accumulation of i(na) into an intermediate inactivated state, but these effects were abolished by mutating either of these sites to non-phosphorylatable ala residues.	SIGNOR-197058
P35813	Q14653	1	dephosphorylation	down-regulates activity	0.247	In contrast, coexpression of wild-type PPM1A, but not its D239N or R174G mutant, abolished IRF3 activation (XREF_FIG).\|We found that PPM1A abolished the C-terminal phosphorylation of IRF3 (XREF_FIG), whereas depletion of PPM1A expression improved virus induced pIRF3 level (XREF_FIG and XREF_FIG).	SIGNOR-277152
Q9NPD8	Q9NW38	2	ubiquitination	up-regulates activity	0.901	Using the Fanconi Anemia pathway exclusive E3-E2 pair, FANCL-Ube2T, we report the atomic structure of the FANCL RING-Ube2T complex\|Our structural and biochemical analyses suggest that, in a cellular environment with multiple E2s present, FANCL will preferentially select Ube2T.	SIGNOR-263263
P10276	P48443	2	binding	up-regulates	0.669	Here we report that the transcriptional activity of rar and rxr can be reciprocally modulated by direct interactions between the two proteins	SIGNOR-16466
Q99704	P26010	2	binding	down-regulates activity	0.324	Integrins also bind to many PTBdomain-containing proteins (Calderwood et al., 2003) – including Dok1 and integrincytoplasmic-domain-associated protein 1 (ICAP1) – and these can compete with talin for binding to integrin and so can impair activation	SIGNOR-257695
P62820	O43318	0	phosphorylation	up-regulates activity	0.2	TAK1 preferentially phosphorylates the inactive (GDP-bound) state of Rab1. Phosphorylation of Rab1 disrupts interaction with GDP dissociation inhibitor 1 (GDI1), but not guanine exchange factor (GEF) or GTPase-activating protein (GAP) enzymes, and is exclusive to membrane-localized Rab1, suggesting phosphorylation may stimulate Rab1 membrane association. Furthermore, we found phosphorylation of Rab1 at T75 to be essential for Rab1 function.	SIGNOR-277270
O43521	O14965	0	phosphorylation	down-regulates quantity by destabilization	0.376	We observed that BimEL is phosphorylated by Aurora A early in mitosis and reversed by PP2A after mitotic exit. Aurora A phosphorylation stimulated binding of BimEL to the F-box protein beta-transducin repeat containing E3 ubiquitin protein ligase and promoted ubiquitination and degradation of BimEL.	SIGNOR-276248
P42574	O76075	1	cleavage	up-regulates	0.684	Casp3_ cleaves the 45 kda subunit at two sites to generate an active factor that produces_ dna_ fragmentation	SIGNOR-47419
Q6IAA8	Q05086	0	ubiquitination	down-regulates quantity by destabilization	0.2	Ube3a regulates mTORC1 signaling by targeting p18, a subunit of the Ragulator. Ube3a ubiquinates p18, resulting in its proteasomal degradation, and Ube3a deficiency in the hippocampus of AS mice induces increased lysosomal localization of p18 and other members of the Ragulator-Rag complex, and increased mTORC1 activity	SIGNOR-256145
P19544	Q02962	2	transcriptional regulation	down-regulates quantity by repression	0.598	A marked increase in WT1 protein levels coincided precisely with down-regulation of the Pax-2 gene in the individual precursor cells of the visceral glomerular epithelium, suggesting a direct effect of the WT1 repressor protein on Pax-2 regulatory elements. To examine whether WT1 could directly repress Pax-2 transcription, binding of WT1 to three high affinity sites in the 5' untranslated Pax-2 leader sequence was demonstrated by DNAseI footprinting analysis	SIGNOR-252298
P28482	Q16665	1	phosphorylation	up-regulates	0.586	We show that at least two different nuclear protein kinases, one of them identified as p42/p44 mapk, can modify hif-1_. Analysis of in vitro phosphorylated hif-1_ by mass spectroscopy revealed residues ser-641 and ser-643 as possible mapk phosphorylation sites these data suggest that phosphorylation of ser-641/643 by mapk promotes the nuclear accumulation and transcriptional activity of hif-1_	SIGNOR-178723
Q13131	P29474	1	phosphorylation	up-regulates	0.283	The central finding of this report is that rosiglitazone rapidly stimulates no production and enos ser-1177 phosphorylation in an ampk-dependent manner	SIGNOR-160838
P09758	Q05655	0	phosphorylation	down-regulates activity	0.2	Analyses using HCT116 cells expressing WT Trop-2 (HCT116/WT) or Trop-2 alanine-substituted at Ser-303 (HCT116/S303A) or Ser-322 (HCT116/S322A) revealed that Trop-2 is phosphorylated at Ser-322. sing protein kinase C (PKC) inhibitors and PKC-specific siRNAs, we found that PKCα and PKCδ are responsible for Trop-2 phosphorylation.	SIGNOR-273820
P49146	P01303	2	binding	up-regulates	0.837	Analogs of npy and pyy have been synthesized that contain a proline residue in position 34 of the molecule, i.e., [leu31, pro34]npy (fuhlendorff et al., 1990) or [pro34]pyy (grandt et al., 1994b), and are much more potent at y1 than y2receptors.	SIGNOR-56568
Q9UJ55	O00327	2	binding	down-regulates activity	0.369	Magel2 represses the activity of the Clock:Bmal1 heterodimer in a Per2-luciferase assay. Magel2 interacts with Bmal1 and with Per2 as measured by co-immunoprecipitation in co-transfected cells, and exhibits a subcellular distribution consistent with these interactions when visualized by immunofluorescence. As well, Magel2 induces the redistribution of the subcellular localization of Clock towards the cytoplasm, in contrast to the nucleus-directed effect of Bmal1 on Clock subcellular localization.	SIGNOR-253517
P17612	P31323	2	phosphorylation	up-regulates activity	0.881	Serine 114 phosphorylation is required for both nuclear localization and down-regulation of il-2 production by riibeta.	SIGNOR-125545
P27361	Q96RK0	1	phosphorylation	down-regulates	0.374	Specifically, 14-3-3 binds to p90(rsk)-phosphorylated ser?_??_ Of capic?_A thereby modulating dna binding to its hmg (high-mobility group) box, whereas erk phosphorylations prevent binding of a c-terminal nls (nuclear localization sequence) to importin ?4 (kpna3)[...] These results suggest that erk phosphorylation of ser1382 and ser1409 masks the nls and prevents its binding to kpna3	SIGNOR-169879
P10523	P46934	0	polyubiquitination	down-regulates quantity by destabilization	0.373	Here we report that NEDD4-1, a HECT domain-containing E3 ubiquitin ligase, binds via its HECT domain directly with SAG's C-terminal RING domain and ubiquitylates SAG for proteasome-mediated. We also found that SAG bridges NEDD4-1 via its C-terminus and CUL-5 via its N-terminus to form a NEDD4-1/SAG/CUL-5 tri-complex. Biologically, NEDD4-1 overexpression sensitizes cancer cells to etoposide-induced apoptosis by reducing SAG levels through targeted degradation. Thus, SAG is added to a growing list of NEDD4-1 substrates and mediates its biological function. degradation.	SIGNOR-272843
O75030	P27361	0	phosphorylation	down-regulates quantity by destabilization	0.542	More interestingly, ERK-dependent phosphorylation of MITF at Ser 73 is essential for MITF ubiquitinilation and degradation (87). Putting together all these findings, it can be proposed that MAPK activation inhibits melanogenesis due to an increased MITF degradation which is dependent on the MAPK-induced MITF phosphorylation and ubiquitinilation. In summary, although the phosphorylation of MITF at Ser73 increases its intrinsic transcriptional activity, this phosphorylation also targets MITF to the proteasome for its degradation. Consequently, the decrease in MITF levels leads to a down-regulation of melanogenic enzymes expression and to an inhibition of melanogenesis.	SIGNOR-249620
Q13467	O00744	2	binding	up-regulates	0.619	Inhibition of adipogenesis by wnt10b is likely mediated by‚ wnt‚ receptors, frizzled 1, 2, and/or 5, and co-receptors low density lipoprotein receptor-related proteins 5 and 8	SIGNOR-210164
Q05209	P17252	0	phosphorylation	down-regulates	0.322	Ptp-pest is phosphorylated in vitro by both cyclic amp-dependent protein kinase (pka) and protein kinase c (pkc) at two major sites, which we have identified as ser39 and ser435 / phosphorylation of ser39 in vitro decreases the activity of ptp-pest by reducing its affinity for substrate.	SIGNOR-27300
Q14814	P56524	2	binding	down-regulates	0.692	We discovered that mef2 interacts with histone deacetylases (hdacs) 4 and 5, resulting in repression of the transcriptional activity of mef2.	SIGNOR-76237
P48729	O60346	1	phosphorylation	down-regulates quantity by destabilization	0.309	We show that the beta-TrCP-mediated degradation requires phosphorylation of PHLPP1 by casein kinase I and glycogen synthase kinase 3beta (GSK-3beta), and activation of the phosphatidylinositol 3-kinase/Akt pathway suppresses the degradation of PHLPP1 by inhibiting the GSK-3beta activity.	SIGNOR-276262
Q13177	Q15746	1	phosphorylation	down-regulates activity	0.533	PAK2 can directly phosphorylate MLCK, inhibiting its activity and limiting the development of isometric tension. PAK2 catalyzes MLCK phosphorylation on serine residues 439 and 991.	SIGNOR-250223
P17252	P35612	1	phosphorylation	down-regulates	0.2	We now demonstrate that ptn stimulates the phosphorylation of serines 713 and 726 in the myristoylated alanine-rich protein kinase (pk) c substrate domain of beta-adducin through activation of either pkc alpha or beta.	SIGNOR-139870
O14641	Q9NYF0	2	binding	down-regulates	0.791	Dapper 1 antagonizes wnt signaling by promoting dishevelled degradation	SIGNOR-144053
P14136	P17252	0	phosphorylation	down-regulates activity	0.366	Glial fibrillary acidic protein (GFAP), the intermediate filament component of astroglial cells, can serve as an excellent substrate for both cAMP-dependent protein kinase and protein kinase C, in vitro. GFAP phosphorylated by each protein kinase does not polymerize, and the filaments that do polymerize tend to depolymerize after phosphorylation. Dephosphorylation of phospho-GFAP by phosphatase led to a recovery of the polymerization competence of GFAP. Most of the phosphorylation sites for cAMP-dependent protein kinase and protein kinase C on GFAP are the same, Ser-8, Ser-13, and Ser-34. cAMP-dependent protein kinase has one additional phosphorylation site, Thr-7.	SIGNOR-248862
P00533	Q14185	1	phosphorylation	up-regulates activity	0.308	Here we report that EGFRvIII induces serine phosphorylation at serine residue 1250 (S1250) of Dock180 (p-Dock180 S1250 ) and that p-Dock180 S1250 is required for EGFRvIII-promoted Rac1 activation, glioblastoma cell growth, survival and invasion in vitro and in vivo .\|We demonstrate that EGFRvIII induces serine phosphorylation of Dock180, stimulates Rac1 activation and glioma cell migration.	SIGNOR-279329
P19484	P04062	1	transcriptional regulation	up-regulates quantity by expression	0.325	Nucleus-Translocated ACSS2 Promotes Gene Transcription for Lysosomal Biogenesis and Autophagy\|A chromatin immunoprecipitation (ChIP) assay with antibodies against TFEB or ACSS2 demonstrated that glucose deprivation results in the binding of TFEB (Figure 3D) and ACSS2 (Figure 3E) to the promoter regions of CTSA, GBA, GUSB, and LAMP1\|These results indicated that TFEB and ACSS2 are mutually required for their binding to the promoter regions of lysosomal genes. In line with these findings, glucose deprivation induced mRNA (Figure 3F) and protein (Figure 3G) expression for these lysosomal genes, which was largely abrogated by knockin of ACSS2 mutants	SIGNOR-276551
P50148	Q13304	2	binding	up-regulates activity	0.385	Here we systematically quantified ligand-induced interactions between 148 GPCRs and all 11 unique G alpha subunit C-termini. For each receptor, we probed chimeric G alpha subunit activation via a transforming growth factor-alpha (TGF alpha) shedding response in HEK293 cells lacking endogenous Gq/11- and G12/13- signaling. \| We defined positive coupling if any member of the subfamily scored LogRAi ≥ -1 and negative coupling if all of the members scored LogRAi < -1 (Figure 3A-B). ROC analysis gives AUC = 0.78 (Figure S4A) when considering high-confidence known coupling data and suggested a threshold of LogRAi ≥ -1.0 for defining true couplings. \| The score associated to this interaction has a LogRAi ≥ -1.0.	SIGNOR-257087
P28482	P67809	1	phosphorylation	up-regulates activity	0.47	ERK2 may also directly phosphorylate YB-1 and therefore promotes its ability to transactivate target genes.	SIGNOR-279227
Q92574	P49815	2	binding	up-regulates activity	0.934	Furthermore, tsc2 is directly phosphorylated by akt, which is involved in stimulating cell growth and is activated by growth stimulating signals, such as insulin. Tsc2 is inactivated by akt-dependent phosphorylation, which destabilizes tsc2 and disrupts its interaction with tsc1.	SIGNOR-77400
P25054	P11926	1	transcriptional regulation	down-regulates quantity by repression	0.268	APC-dependent regulation of ornithine decarboxylase in human colon tumor cells\|Upon induction of APC expression, ODC promoter activity and RNA levels were suppressed	SIGNOR-253670
P06748	P31269	1	transcriptional regulation	down-regulates quantity by repression	0.352	In AML cells, NPM1 mutations result in abnormal cytoplasmic localization of the mutant protein (NPM1c); however, it is unknown whether NPM1c is required to maintain the leukemic state. Here, we show that loss of NPM1c from the cytoplasm, either through nuclear relocalization or targeted degradation, results in immediate downregulation of homeobox (HOX) genes followed by differentiation.	SIGNOR-260138
P07478	P55085	1	cleavage	up-regulates activity	0.2	PAR1E and PAR2E (10 microM) were incubated in the presence of the different proteases \| The enzymes were used at the following concentrations: 0.5 unit/mL thrombin, 2.5 nM trypsin, 20 nM plasmin, 20 nM cathepsin G, 20 nM elastase, 20 nM proteinase 3, and 2 units/mL calpain I and II\|Protease-activated receptors (PARs) mediate cell activation after proteolytic cleavage of their extracellular amino terminus.\|Mass spectrometry studies of PAR2E predicted activation of PAR2 by trypsin through cleavage at the Arg36-Ser37 site, no effect of thrombin, and inactivation of the receptor by plasmin, calpain and leukocyte elastase, cathepsin G, and proteinase 3	SIGNOR-263606
O43315	Q8TD84	2	binding	up-regulates activity	0.2	Our findings now further suggest that STAT3 and the adaptor protein SH2D2A interact with tyrosine‐containing motifs within the DSCAM/L1 ICDs. The SH2 domains of both STAT3 and SH2D2A are known to bind to phosphorylated tyrosine residues in the context of such motifs. Thus, the interactions between DSCAMs and SH2‐domain containing proteins seem to play a central and conserved role in Dscam signaling in the context of dynamic changes of tyrosine‐phosphorylation levels.	SIGNOR-264280
O43294	P06241	0	phosphorylation	up-regulates activity	0.34	Hic-5 is a CAKbeta-binding protein localized at focal adhesions. Here we show that overexpression of CAKbeta or Fyn, but not FAK, enhanced the tyrosine phosphorylation of coexpressed Hic-5 in COS-7 cells. The Y60F mutant of Hic-5 was not phosphorylated, and Hic-5 phosphorylated on tyrosine 60 was bound specifically to the SH2 domain of Csk. Specific phosphorylation of Hic-5 by CAKbeta and Fyn may activate a signaling pathway mediated by Hic-5.	SIGNOR-262875
Q8IXJ6	P18669	1	deacetylation	up-regulates activity	0.279	Here we report that PGAM is acetylated at lysine 100 (K100), an active site residue that is invariably conserved from bacteria, to yeast, plant, and mammals. K100 acetylation is detected in fly, mouse, and human cells and in multiple tissues and decreases PGAM2 activity. The cytosolic protein deacetylase sirtuin 2 (SIRT2) deacetylates and activates PGAM2.	SIGNOR-266517
Q13554	Q9UBS5	1	phosphorylation	down-regulates quantity by destabilization	0.2	ERK1/2 and CaMKIIβ mediated phosphorylation of GABAB1 at serine 867 (S867) and threonine 872 (T872). We found that, in addition to CaMKIIβ, also ERK1/2 is involved in the degradation pathway of GABAB receptors under physiological and ischemic conditions. In contrast to our previous view, CaMKIIβ does not appear to directly phosphorylate S867. Instead, the data support a mechanism in which CaMKIIβ activates ERK1/2, which then phosphorylates S867 and T872 in GABAB1.	SIGNOR-277851
P17542	Q99816	1	polyubiquitination	down-regulates quantity by destabilization	0.2	These data suggest that Tal mediates polyubiquitylation of the lysine residues in the VPS28-binding region of TSG101, leading to subsequent degradation of TSG101.	SIGNOR-271636
P31946	Q05655	0	phosphorylation	down-regulates	0.493	We provide a mechanism for these observations through the phosphorylation of 14-3-3 by ikk and pkc on serine residues ser132 and ser60, respectively, which interferes with its binding to ttp and hence the retention of ttp in the cytoplasm.	SIGNOR-138612
P53350	Q9H1A4	1	phosphorylation	up-regulates	0.524	Our analysis revealed an unexpected and unprecedented complexity of mitotic phosphorylation sites and suggests that other kinases than cdk1 and plk1 also contribute to apc phosphorylation.	SIGNOR-119881
P08754	O14843	2	binding	up-regulates activity	0.2	Here we systematically quantified ligand-induced interactions between 148 GPCRs and all 11 unique G alpha subunit C-termini. For each receptor, we probed chimeric G alpha subunit activation via a transforming growth factor-alpha (TGF alpha) shedding response in HEK293 cells lacking endogenous Gq/11- and G12/13- signaling. \| We defined positive coupling if any member of the subfamily scored LogRAi ≥ -1 and negative coupling if all of the members scored LogRAi < -1 (Figure 3A-B). ROC analysis gives AUC = 0.78 (Figure S4A) when considering high-confidence known coupling data and suggested a threshold of LogRAi ≥ -1.0 for defining true couplings. \| The score associated to this interaction has a LogRAi ≥ -1.0.	SIGNOR-256821
Q96RU7	P31749	2	binding	down-regulates activity	0.619	TRB3 expression is induced in liver under fasting conditions, and TRB3 disrupts insulin signaling by binding directly to Akt and blocking activation of the kinase.	SIGNOR-252644
Q9Y2W1	P23246	2	binding	down-regulates	0.436	Here we demonstrate that in resting tcells psf is directly phosphorylated by gsk3, thus promoting interaction of psf with trap150, which prevents psf from binding cd45 pre-mrna. Upon tcell activation, reduced gsk3 activity leads to reduced psf phosphorylation, releasing psf from trap150 and allowing it to bind cd45 splicing regulatory elements and repress exon inclusion.	SIGNOR-168441
P08754	P61073	2	binding	up-regulates activity	0.478	Using this model, we have reported that CXCL12 activates Gi1, Gi2, or Gi3 heterotrimeric G proteins in a concentration-dependent manner	SIGNOR-278104
P63096	O43306	2	binding	down-regulates activity	0.541	Types V and VI adenylyl cyclase are most sensitive to inhibition by Gnai1, Gnai2, and Gnai3	SIGNOR-278077
Q13127	O60741	1	transcriptional regulation	down-regulates quantity by repression	0.2	Levels of NRSF and its physical binding to the Hcn1 gene were augmented after SE, resulting in repression of HCN1 expression and HCN1-mediated currents (I(h) ), and reduced I(h) -dependent resonance in hippocampal CA1 pyramidal cell dendrites.	SIGNOR-268970
Q8TDI8	O75838	2	binding	up-regulates activity	0.334	Furthermore, we report that calcium and integrin-binding protein 2 binds to the components of the hair cell mechanotransduction complex, TMC1 and TMC2, and these interactions are disrupted by deafness-causing Cib2 mutations. We conclude that calcium and integrin-binding protein 2 is required for normal operation of the mechanotransducer channels and is involved in limiting the growth of transducing stereocilia.	SIGNOR-269664
P41968	P19086	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-257142
Q03164	Q01196	2	binding	up-regulates quantity by stabilization	0.568	Similar to CBFβ, we show that MLL binds to AML1 abrogating its proteasome-dependent degradation.Furthermore, we demonstrate that MLL binds to a region of AML1 (that is conserved in AML2 and AML3) and increases AML1 (AML2 and AML3) protein levels	SIGNOR-255707
Q16665	P13674	1	transcriptional regulation	up-regulates quantity by expression	0.314	Hypoxia upregulates P4HA1 expression in PDAC PDOs through HIF1α. Our results show that the treatment of PDO4 and PDO11 cells with 10 μmol/L of PX-478 for 24 hours reduced the levels of P4HA1 in hypoxia (Fig. 2F), suggesting P4HA1 expression in hypoxia is regulated by HIF1α expression.	SIGNOR-279840
Q9ULH7	P11831	2	binding	up-regulates activity	0.2	MKL2 binds to and activates SRF similar to myocardin and MKL1.	SIGNOR-237671
P09471	P50406	2	binding	up-regulates activity	0.252	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-257186
Q8NG66	P30304	1	phosphorylation	down-regulates	0.417	Nek11 regulates cdc25a degradation and the ir-induced g2/m checkpointincubation of wild-type cdc25a with nek11 led to a marked increase in phosphorylation of ser 82 and 88 as detected with the phosphospecific antibody recognizing these sites	SIGNOR-187867
P61278	P51608	0	post transcriptional regulation	up-regulates quantity by expression	0.297	MeCP2 binds to the promoter region of six target genes. ChIP with anti-MeCP2 antibody shows that MeCP2 binds to the promoter regions of activated targets Sst, Oprk1, Gamt, and Gprin1, and repressed targets Mef2c and A2bp1.	SIGNOR-264676
P53779	Q00535	0	phosphorylation	down-regulates activity	0.345	Here, we show that cdk5 directly phosphorylates c-Jun N-terminal kinase 3 (JNK3) on Thr131 and inhibits its kinase activity, leading to reduced c-Jun phosphorylation.	SIGNOR-250668
Q6JBY9	Q16644	0	phosphorylation	down-regulates activity	0.482	Human CapZIP was phosphorylated at Ser-179 and Ser-244 by MAPKAP-K2 (mitogen-activated protein kinase-activated protein kinase 2) or MAPKAP-K3 in vitro. In the present paper we have identified CapZIP as a protein that is phosphorylated exceptionally rapidly by several SAPKs in vitro (Figure 4), and which is expressed in muscles and immune cells. Both MAPKAP-K2 and MAPKAP-K3 phosphorylated CapZIP at Ser-179 in vitro. An important clue to the function of CapZIP and its phosphorylation came from the finding that it binds to the actin-capping protein CapZ (Figure 7A), and that cellular stresses trigger the dissociation of these two proteins (Figure 7B).Such an effect is presumably lost when CapZIP is phosphorylated and dissociates from CapZ.	SIGNOR-263082
O43186	Q02446	2	binding	up-regulates activity	0.388	Sp4 directly binds Crx. Sp4 and Sp1 produce much higher levels of transcriptional activation when co-transfected with Crx, they may additionally act by directly increasing the rate of transcriptional initiation by the general transcriptional apparatus through their activation domains.	SIGNOR-225333
Q9H300	Q15119	0	phosphorylation	up-regulates activity	0.2	As expected, knocking down PDK2 in HEK293 cells that overexpress PARL resulted in a significant increase in beta cleavage in comparison to the control cells.\|Furthermore, we show that PDK2, a key regulator in metabolic plasticity, phosphorylates PARL and regulates \u03b2 cleavage.	SIGNOR-280018
P11831	P05231	1	null	up-regulates	0.281	Srf within myofibers modulates Il6 and Cox2/Il4 expressions and, therefore, exerts a paracrine control of satellite cell proliferation and fusion, respectively, which in turn support skeletal muscle hypertrophy.	SIGNOR-255966
F7VJQ1	Q00535	0	phosphorylation	up-regulates quantity	0.332	Cdk5 phosphorylated PrP induces the aggregation of non phosphorylated PrP.\|Together, these results indicate that S43 is a major Cdk5 phosphorylation site in PrP.	SIGNOR-278920
P08581	P40763	1	phosphorylation	up-regulates activity	0.706	It has been reported that c-Met can activate STAT3 at the endosome and phosphorylated STAT3 induced by c-Met is colocalized with EEA1, an early endosome marker.	SIGNOR-280041
Q13535	P16220	1	phosphorylation	down-regulates	0.347	Atm phosphorylated creb in vitro and in vivo in response to ionizing radiation (ir) and h(2)o(2) on a stress-inducible domain. Ir-induced phosphorylation of creb correlated with a decrease in creb transactivation potential and reduced interaction between creb and its transcriptional coactivator, creb-binding protein (cbp). A creb mutant containing ala substitutions at atm phosphorylation sites displayed enhanced transactivation potentialit is, therefore, likely that atm and atr regulate creb phosphorylation collectively in response to stress stimuli.	SIGNOR-124060

Q2M1Z3

P49841

0

phosphorylation

up-regulates activity

0.302

We show that GSK-3alpha and -beta interact with CdGAP in mammalian cells. We also demonstrate that GSK-3 phosphorylates CdGAP both in vitro and in vivo on Thr-776, which we have previously shown to be an ERK 1/2 phosphorylation site involved in CdGAP regulation.

SIGNOR-262879

P35612

P17612

0

phosphorylation

down-regulates activity

0.283

Ser-726 and Ser-713 in the C-terminal MARCKS-related domains of - and -adducin, respectively, were identified as the major phosphorylation sites common for PKA and PKC. Phosphorylation by PKA, but not PKC, reduced the affinity of adducin for spectrin-F-actin complexes as well as the activity of adducin in promoting binding of spectrin to F-actin.

SIGNOR-250332

Q92769

P19784

0

phosphorylation

up-regulates activity

0.39

HDAC2 is phosphorylated uniquely by protein kinase CK2 in vitro. Studies using unfractionated cell extracts with CK2 inhibitors suggest that protein kinase CK2 is the major source of HDAC2 kinase. Finally, and perhaps most interesting, HDAC2 phosphorylation promotes enzymatic activity, selectively regulates complex formation, but has no effect on transcriptional repression. | Since our data suggest that protein kinase CK2 is the major kinase responsible for HDAC2 phosphorylation, and because Ser422 and Ser424, but not Ser411, lie within CK2 recognition sequences, we believe that Ser394, Ser422, and Ser424 constitute the three phosphorylated residues in HDAC2.

SIGNOR-251001

P17612

Q16891

1

phosphorylation

down-regulates activity

0.2

PKA directly phosphorylated the Ser528 residue of MIC60. Phosphorylation of MIC60 Interrupts Parkin Recruitment and Formation of the MICOS Complex

SIGNOR-266302

Q96EP0

P29466

2

polyubiquitination

up-regulates activity

0.2

HOIP forms a constitutive interaction with caspase-1 and mediates the linear ubiquitination of the CARD pro-domain. Upon engagement of apoptosis, caspase-1 and caspase-8 cleave HOIP at Asp-348 and Asp-387, limiting the ability of LUBAC to ubiquitinate substrates.

SIGNOR-272191

P12931

P19174

1

phosphorylation

up-regulates activity

0.636

The phosphorylation of purified phospholipase C-gamma 1 (PLC-gamma 1) and PLC-gamma 2 by src-family-protein tyrosine kinases (PTKs) P56lck, p53/56lyn, p59hck, p59fyn, and p60src was studied in vitro. All five PTKs phosphorylated PLC-gamma 1 and PLC-gamma 2, suggesting that both PLC-gamma isozymes can be phosphorylated in cells by any of the src-family PTKs in response to the activation of cell surface receptors.

SIGNOR-247316

O14983

P16157

2

binding

down-regulates activity

0.293

We recently reported that small ankyrin 1 (sAnk1) interacts with the sarco(endo)plasmic reticulum Ca2+-ATPase in skeletal muscle (SERCA1) to inhibit its activity.

SIGNOR-265927

P19086

Q96RI0

2

binding

up-regulates activity

0.2

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

SIGNOR-257312

P14598

P28482

0

phosphorylation

up-regulates

0.45

Erk1/2 are the kinases involved in p47phox_ phosphorylation on ser345 in gm-csfprimed human neutrophils._ Phosphorylation of ser345 is required for the priming of nadph oxidase activity in neutrophil-like cells

SIGNOR-147170

P42261

Q15818

2

binding

up-regulates activity

0.296

We found that NP1 colocalizes and physically associates with the fast excitatory GluR1 AMPA receptors and that hypoxia induces a time-dependent increase in the NP1-GluR1 interactions. Thus hypoxia recruits NP1 protein to GluR1 subunits concurrent with the hypoxic excitotoxic cascade.|Rather we propose that through interactions with GluR1 clusters, NP1 modulates the function of AMPA receptors in a manner whereby increased NP1-GluR1 interactions sensitize neurons to hypoxia-induced excitotoxic death.

SIGNOR-261430

P12931

O14578

1

phosphorylation

up-regulates activity

0.273

CitK is tyrosine phosphorylated by Src in response to EphB2 signaling.

SIGNOR-279484

P0DP24

P16298

2

binding

up-regulates

0.511

Calcium-bound calmodulin associates with calcineurin (cn), releasing the phosphatase from the repressive effects on an autoinhibitory domain.

SIGNOR-266322

P12757

Q13485

2

binding

down-regulates activity

0.886

Thus, SnoN can interact with Smad4 and Smad2 and inhibit their abilities to activate transcription.

SIGNOR-71633

Q13639

P63096

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-257041

Q8IUC6

O00206

2

binding

up-regulates activity

0.85

To initiate the innate immune response, Toll-like receptors (TLRs) associate with cytoplasmic adaptor proteins through TIR (Toll/interleukin-1 receptor) domain interactions. The four principal signaling adaptor proteins include MyD88, MAL, TRIF and TRAM, and the fifth protein SARM, involved in negative regulation of TLR pathways, is usually considered a part of the TIR domain-containing adaptor protein group

SIGNOR-252067

P31749

Q15121

1

phosphorylation

up-regulates activity

0.517

Protein kinase b/akt binds and phosphorylates ped/pea-15, stabilizing its antiapoptotic action.

SIGNOR-102092

P67775

Q9Y570

0

demethylation

down-regulates activity

0.905

Methylation of the carboxy-terminal Leu309 in a conserved TPDYFL309 motif of the C subunit has been shown to enhance the affinity of the PP2A core enzyme for some, but not all, regulatory subunits |Demethylation and negative regulation of PP2A is mediated by a PP2A-specific methylesterase PME-1, which is conserved from yeast to humans.

SIGNOR-265748

Q96RJ3

Q9Y275

2

binding

up-regulates activity

0.785

Baff specifically binds baff receptor

SIGNOR-135713

P43629

P68400

0

phosphorylation

up-regulates quantity by stabilization

0.2

Functional studies of the wild-type receptor and serine/threonine mutants indicated that phosphorylation of Ser(394) by protein kinase C slightly suppresses KIR3DL1 inhibitory function, and reduces receptor internalization and turnover.Both CKII and PKC phosphorylate KIR3DL1 in vitro. Ser364 can be phosphorylated after phosphorylation of Ser367 by CKII. It seems that phosphorylation of 3DL1 by CK does not significantly affect receptor inhibitory function or turnover, at least in the assays that we have used so far.

SIGNOR-276077

O00744

Q9NPG1

2

binding

up-regulates

0.617

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

SIGNOR-131625

Q13315

2

phosphorylation

up-regulates activity

0.2

In human cells, the activation process involves autophosphorylation on three sites (ser367, ser1893, and ser1981) and acetylation on lys3016. We now describe the identification of a new atm phosphorylation site, thr(p)1885 and an additional autophosphorylation site, ser(p)2996, that is highly dna damage-inducible.

SIGNOR-170477

P53350

Q12834

1

phosphorylation

down-regulates quantity by destabilization

0.977

Plk1 directly bound to Cdc20 and phosphorylates it on serine-170 located in CRY-box. Whereas wild-type Cdc20 was degraded according to progress cell cycle beyond mitosis, the phosphorylation-defective mutant, which serine-170 was changed into alanine, was not destroyed in early G1 phase.

SIGNOR-276493

P08069

Q92569

2

binding

up-regulates

0.807

Moreover, we found that the insulin-like growth factor-1 receptor (igf-ir) bound to p55pik;the interaction occurred at the receptor tyrosine 1316 and involved both p55pik sh2 domains.

SIGNOR-52683

P56524

Q96GD4

0

phosphorylation

down-regulates

0.264

We define the precise site of aurb-mediated phosphorylation as a conserved serine within the nuclear localization signals of hdac4, hdac5, and hdac9 at ser265, ser278, and ser242, respectivelyduring mitosis, aurb-mediated phosphorylation may localize class iia hdacs to a phosphorylation gradient at the spindle midzone, permitting temporal and spatial regulatory mechanisms altering hdac protein interactions

SIGNOR-198646

Q08999

Q92878

2

binding

up-regulates activity

0.304

We propose that p130, forming a complex with Rad50 through RINT-1, blocks telomerase-independent telomere lengthening in normal cells.

SIGNOR-265029

Q13976

P78347

1

phosphorylation

up-regulates

0.569

G-kinase phosphorylated tfii-i in vitro and in vivo on ser(371) and ser(743) outside of the interaction domain. G-kinase strongly enhanced tfii-i transactivation of a serum-response element-containing promoter in cos7 cells

SIGNOR-89849

P17252

P29353

1

phosphorylation

up-regulates activity

0.401

Among them, Ser(29) in p52(Shc) (equivalent to Ser(138) in p66(Shc)) was phosphorylated only after TPA stimulation. Phosphorylation of this site together with the intact phosphotyrosine-binding domain was essential for ShcA binding to the protein-tyrosine phosphatase PTP-PEST. TPA-induced ShcA phosphorylation at this site (and hence, its association with PTP-PEST) was inhibited by a protein kinase C-specific inhibitor and was induced by overexpression of constitutively active mutants of protein kinase Calpha, -epsilon, and -delta isoforms.

SIGNOR-249150

O95239

O14965

0

phosphorylation

up-regulates activity

0.419

We show that Aurora A phosphorylates the condensin I-dependent pool of KIF4A and thus actively promotes chromosome congression from the spindle poles to the metaphase plate. In vitro kinase assays showed that recombinant KIF4A can be phosphorylated by Aurora A and that this activity is inhibited by the specific Aurora A inhibitor MLN8537 (Fig. 7 C).

SIGNOR-265993

P43405

Q13261

1

phosphorylation

up-regulates activity

0.329

Mutation of a defined region of the intracellular signaling portion of IL-15Ralpha (Tyr227) abrogates both the IL-15Ralpha/Syk association and IL-15Ralpha phosphorylation. Taken together, this suggests that Syk kinase physically and functionally associates with the IL-15Ralpha chain in B cells and that Syk plays a key role in mediating IL-15-induced signal transduction, thus accounting for the distinct functional consequences of IL-15 vs IL-2 binding to B cells

SIGNOR-246556

Q8N6F7

P62993

2

binding

down-regulates activity

0.2

Herein, we demonstrate that the adaptor protein HGAL, specifically expressed in GC lymphocytes and GC-derived lymphomas, directly binds to Grb2 upon BCR activation and negates the inhibitory effects of Grb2 on the BCR-induced biochemical signaling cascade.

SIGNOR-273608

P30304

P49137

0

phosphorylation

down-regulates

0.364

Mk2 was required for the degradation of cdc25a. Mk2 phosphorylates cdc25a in vitro. Phosphorylation of cdc25a in vivo has been shown to facilitate its ubiquitin-mediated proteolysis

SIGNOR-152996

Q58F21

P62805

0

relocalization

up-regulates activity

0.2

BRDT interacts with acetylated nucleosomes via its BD1 domain. Binding may be initiated through non-specific interactions with DNA, which allow BRDT to localize to chromatin. Specificity is generated through recognition of tandem acetylated lysine residues (K5ac/K8ac) on the histone H4 tail,

SIGNOR-262066

O00139

Q6IQ55

0

phosphorylation

down-regulates activity

0.406

TTBK2 phosphorylates KIF2A primarily at growing MT ends and counteracts the depolymerization activity of KIF2A

SIGNOR-260926

Q15911

Q14258

0

polyubiquitination

down-regulates quantity by destabilization

0.451

In the present study we show that EFP (oestrogen-responsive finger protein) is an E3 ubiquitin ligase mediating oestrogen-induced ATBF1 protein degradation. Knockdown of EFP increases ATBF1 protein levels, whereas overexpression of EFP decreases ATBF1 protein levels.

SIGNOR-272048

Q5XX13

P04406

1

polyubiquitination

up-regulates activity

0.2

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

SIGNOR-277841

P27361

Q02548

1

phosphorylation

down-regulates activity

0.247

In this study, we demonstrated that PAX5 was phosphorylated by ERK1/2 in vitro and in vivo at serines 189 and 283. This phosphorylation attenuated the transcriptional repression of BLIMP1 by PAX5.

SIGNOR-269086

Q14524

Q13557

0

phosphorylation

down-regulates

0.492

A stable interaction between ?(C)-camkii and the intracellular loop between domains 1 and 2 of na(v)1.5 was observed. This region was also phosphorylated by ?(C)-camkii, specifically at the ser-516 and thr-594 sites.Wild-type (wt) and phosphomutant hna(v)1.5 were co-expressed with gfp-?(C)-camkii in hek293 cells, and i(na) was recorded. As observed in myocytes, camkii shifted wt i(na) availability to a more negative membrane potential and enhanced accumulation of i(na) into an intermediate inactivated state, but these effects were abolished by mutating either of these sites to non-phosphorylatable ala residues.

SIGNOR-197058

P35813

Q14653

1

dephosphorylation

down-regulates activity

0.247

In contrast, coexpression of wild-type PPM1A, but not its D239N or R174G mutant, abolished IRF3 activation (XREF_FIG).|We found that PPM1A abolished the C-terminal phosphorylation of IRF3 (XREF_FIG), whereas depletion of PPM1A expression improved virus induced pIRF3 level (XREF_FIG and XREF_FIG).

SIGNOR-277152

Q9NPD8

Q9NW38

2

ubiquitination

up-regulates activity

0.901

Using the Fanconi Anemia pathway exclusive E3-E2 pair, FANCL-Ube2T, we report the atomic structure of the FANCL RING-Ube2T complex|Our structural and biochemical analyses suggest that, in a cellular environment with multiple E2s present, FANCL will preferentially select Ube2T.

SIGNOR-263263

P10276

P48443

2

binding

up-regulates

0.669

Here we report that the transcriptional activity of rar and rxr can be reciprocally modulated by direct interactions between the two proteins

SIGNOR-16466

Q99704

P26010

2

binding

down-regulates activity

0.324

Integrins also bind to many PTBdomain-containing proteins (Calderwood et al., 2003) – including Dok1 and integrincytoplasmic-domain-associated protein 1 (ICAP1) – and these can compete with talin for binding to integrin and so can impair activation

SIGNOR-257695

P62820

O43318

0

phosphorylation

up-regulates activity

0.2

TAK1 preferentially phosphorylates the inactive (GDP-bound) state of Rab1. Phosphorylation of Rab1 disrupts interaction with GDP dissociation inhibitor 1 (GDI1), but not guanine exchange factor (GEF) or GTPase-activating protein (GAP) enzymes, and is exclusive to membrane-localized Rab1, suggesting phosphorylation may stimulate Rab1 membrane association. Furthermore, we found phosphorylation of Rab1 at T75 to be essential for Rab1 function.

SIGNOR-277270

O43521

O14965

0

phosphorylation

down-regulates quantity by destabilization

0.376

We observed that BimEL is phosphorylated by Aurora A early in mitosis and reversed by PP2A after mitotic exit. Aurora A phosphorylation stimulated binding of BimEL to the F-box protein beta-transducin repeat containing E3 ubiquitin protein ligase and promoted ubiquitination and degradation of BimEL.

SIGNOR-276248

P42574

O76075

1

cleavage

up-regulates

0.684

Casp3_ cleaves the 45 kda subunit at two sites to generate an active factor that produces_ dna_ fragmentation

SIGNOR-47419

Q6IAA8

Q05086

0

ubiquitination

down-regulates quantity by destabilization

0.2

Ube3a regulates mTORC1 signaling by targeting p18, a subunit of the Ragulator. Ube3a ubiquinates p18, resulting in its proteasomal degradation, and Ube3a deficiency in the hippocampus of AS mice induces increased lysosomal localization of p18 and other members of the Ragulator-Rag complex, and increased mTORC1 activity

SIGNOR-256145

P19544

Q02962

2

transcriptional regulation

down-regulates quantity by repression

0.598

A marked increase in WT1 protein levels coincided precisely with down-regulation of the Pax-2 gene in the individual precursor cells of the visceral glomerular epithelium, suggesting a direct effect of the WT1 repressor protein on Pax-2 regulatory elements. To examine whether WT1 could directly repress Pax-2 transcription, binding of WT1 to three high affinity sites in the 5' untranslated Pax-2 leader sequence was demonstrated by DNAseI footprinting analysis

SIGNOR-252298

P28482

Q16665

1

phosphorylation

up-regulates

0.586

We show that at least two different nuclear protein kinases, one of them identified as p42/p44 mapk, can modify hif-1_. Analysis of in vitro phosphorylated hif-1_ by mass spectroscopy revealed residues ser-641 and ser-643 as possible mapk phosphorylation sites these data suggest that phosphorylation of ser-641/643 by mapk promotes the nuclear accumulation and transcriptional activity of hif-1_

SIGNOR-178723

Q13131

P29474

1

phosphorylation

up-regulates

0.283

The central finding of this report is that rosiglitazone rapidly stimulates no production and enos ser-1177 phosphorylation in an ampk-dependent manner

SIGNOR-160838

P09758

Q05655

0

phosphorylation

down-regulates activity

0.2

Analyses using HCT116 cells expressing WT Trop-2 (HCT116/WT) or Trop-2 alanine-substituted at Ser-303 (HCT116/S303A) or Ser-322 (HCT116/S322A) revealed that Trop-2 is phosphorylated at Ser-322. sing protein kinase C (PKC) inhibitors and PKC-specific siRNAs, we found that PKCα and PKCδ are responsible for Trop-2 phosphorylation.

SIGNOR-273820

P49146

P01303

2

binding

up-regulates

0.837

Analogs of npy and pyy have been synthesized that contain a proline residue in position 34 of the molecule, i.e., [leu31, pro34]npy (fuhlendorff et al., 1990) or [pro34]pyy (grandt et al., 1994b), and are much more potent at y1 than y2receptors.

SIGNOR-56568

Q9UJ55

O00327

2

binding

down-regulates activity

0.369

Magel2 represses the activity of the Clock:Bmal1 heterodimer in a Per2-luciferase assay. Magel2 interacts with Bmal1 and with Per2 as measured by co-immunoprecipitation in co-transfected cells, and exhibits a subcellular distribution consistent with these interactions when visualized by immunofluorescence. As well, Magel2 induces the redistribution of the subcellular localization of Clock towards the cytoplasm, in contrast to the nucleus-directed effect of Bmal1 on Clock subcellular localization.

SIGNOR-253517

P17612

P31323

2

phosphorylation

up-regulates activity

0.881

Serine 114 phosphorylation is required for both nuclear localization and down-regulation of il-2 production by riibeta.

SIGNOR-125545

P27361

Q96RK0

1

phosphorylation

down-regulates

0.374

Specifically, 14-3-3 binds to p90(rsk)-phosphorylated ser?_??_ Of capic?_A thereby modulating dna binding to its hmg (high-mobility group) box, whereas erk phosphorylations prevent binding of a c-terminal nls (nuclear localization sequence) to importin ?4 (kpna3)[...] These results suggest that erk phosphorylation of ser1382 and ser1409 masks the nls and prevents its binding to kpna3

SIGNOR-169879

P10523

P46934

0

polyubiquitination

down-regulates quantity by destabilization

0.373

Here we report that NEDD4-1, a HECT domain-containing E3 ubiquitin ligase, binds via its HECT domain directly with SAG's C-terminal RING domain and ubiquitylates SAG for proteasome-mediated. We also found that SAG bridges NEDD4-1 via its C-terminus and CUL-5 via its N-terminus to form a NEDD4-1/SAG/CUL-5 tri-complex. Biologically, NEDD4-1 overexpression sensitizes cancer cells to etoposide-induced apoptosis by reducing SAG levels through targeted degradation. Thus, SAG is added to a growing list of NEDD4-1 substrates and mediates its biological function. degradation.

SIGNOR-272843

O75030

P27361

0

phosphorylation

down-regulates quantity by destabilization

0.542

More interestingly, ERK-dependent phosphorylation of MITF at Ser 73 is essential for MITF ubiquitinilation and degradation (87). Putting together all these findings, it can be proposed that MAPK activation inhibits melanogenesis due to an increased MITF degradation which is dependent on the MAPK-induced MITF phosphorylation and ubiquitinilation. In summary, although the phosphorylation of MITF at Ser73 increases its intrinsic transcriptional activity, this phosphorylation also targets MITF to the proteasome for its degradation. Consequently, the decrease in MITF levels leads to a down-regulation of melanogenic enzymes expression and to an inhibition of melanogenesis.

SIGNOR-249620

Q13467

O00744

2

binding

up-regulates

0.619

Inhibition of adipogenesis by wnt10b is likely mediated by‚ wnt‚ receptors, frizzled 1, 2, and/or 5, and co-receptors low density lipoprotein receptor-related proteins 5 and 8

SIGNOR-210164

Q05209

P17252

0

phosphorylation

down-regulates

0.322

Ptp-pest is phosphorylated in vitro by both cyclic amp-dependent protein kinase (pka) and protein kinase c (pkc) at two major sites, which we have identified as ser39 and ser435 / phosphorylation of ser39 in vitro decreases the activity of ptp-pest by reducing its affinity for substrate.

SIGNOR-27300

Q14814

P56524

2

binding

down-regulates

0.692

We discovered that mef2 interacts with histone deacetylases (hdacs) 4 and 5, resulting in repression of the transcriptional activity of mef2.

SIGNOR-76237

P48729

O60346

1

phosphorylation

down-regulates quantity by destabilization

0.309

We show that the beta-TrCP-mediated degradation requires phosphorylation of PHLPP1 by casein kinase I and glycogen synthase kinase 3beta (GSK-3beta), and activation of the phosphatidylinositol 3-kinase/Akt pathway suppresses the degradation of PHLPP1 by inhibiting the GSK-3beta activity.

SIGNOR-276262

Q13177

Q15746

1

phosphorylation

down-regulates activity

0.533

PAK2 can directly phosphorylate MLCK, inhibiting its activity and limiting the development of isometric tension. PAK2 catalyzes MLCK phosphorylation on serine residues 439 and 991.

SIGNOR-250223

P17252

P35612

1

phosphorylation

down-regulates

0.2

We now demonstrate that ptn stimulates the phosphorylation of serines 713 and 726 in the myristoylated alanine-rich protein kinase (pk) c substrate domain of beta-adducin through activation of either pkc alpha or beta.

SIGNOR-139870

O14641

Q9NYF0

2

binding

down-regulates

0.791

Dapper 1 antagonizes wnt signaling by promoting dishevelled degradation

SIGNOR-144053

P14136

P17252

0

phosphorylation

down-regulates activity

0.366

Glial fibrillary acidic protein (GFAP), the intermediate filament component of astroglial cells, can serve as an excellent substrate for both cAMP-dependent protein kinase and protein kinase C, in vitro. GFAP phosphorylated by each protein kinase does not polymerize, and the filaments that do polymerize tend to depolymerize after phosphorylation. Dephosphorylation of phospho-GFAP by phosphatase led to a recovery of the polymerization competence of GFAP. Most of the phosphorylation sites for cAMP-dependent protein kinase and protein kinase C on GFAP are the same, Ser-8, Ser-13, and Ser-34. cAMP-dependent protein kinase has one additional phosphorylation site, Thr-7.

SIGNOR-248862

P00533

Q14185

1

phosphorylation

up-regulates activity

0.308

Here we report that EGFRvIII induces serine phosphorylation at serine residue 1250 (S1250) of Dock180 (p-Dock180 S1250 ) and that p-Dock180 S1250 is required for EGFRvIII-promoted Rac1 activation, glioblastoma cell growth, survival and invasion in vitro and in vivo .|We demonstrate that EGFRvIII induces serine phosphorylation of Dock180, stimulates Rac1 activation and glioma cell migration.

SIGNOR-279329

P19484

P04062

1

transcriptional regulation

up-regulates quantity by expression

0.325

Nucleus-Translocated ACSS2 Promotes Gene Transcription for Lysosomal Biogenesis and Autophagy|A chromatin immunoprecipitation (ChIP) assay with antibodies against TFEB or ACSS2 demonstrated that glucose deprivation results in the binding of TFEB (Figure 3D) and ACSS2 (Figure 3E) to the promoter regions of CTSA, GBA, GUSB, and LAMP1|These results indicated that TFEB and ACSS2 are mutually required for their binding to the promoter regions of lysosomal genes. In line with these findings, glucose deprivation induced mRNA (Figure 3F) and protein (Figure 3G) expression for these lysosomal genes, which was largely abrogated by knockin of ACSS2 mutants

SIGNOR-276551

P50148

Q13304

2

binding

up-regulates activity

0.385

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

SIGNOR-257087

P28482

P67809

1

phosphorylation

up-regulates activity

0.47

ERK2 may also directly phosphorylate YB-1 and therefore promotes its ability to transactivate target genes.

SIGNOR-279227

Q92574

P49815

2

binding

up-regulates activity

0.934

Furthermore, tsc2 is directly phosphorylated by akt, which is involved in stimulating cell growth and is activated by growth stimulating signals, such as insulin. Tsc2 is inactivated by akt-dependent phosphorylation, which destabilizes tsc2 and disrupts its interaction with tsc1.

SIGNOR-77400

P25054

P11926

1

transcriptional regulation

down-regulates quantity by repression

0.268

APC-dependent regulation of ornithine decarboxylase in human colon tumor cells|Upon induction of APC expression, ODC promoter activity and RNA levels were suppressed

SIGNOR-253670

P06748

P31269

1

transcriptional regulation

down-regulates quantity by repression

0.352

In AML cells, NPM1 mutations result in abnormal cytoplasmic localization of the mutant protein (NPM1c); however, it is unknown whether NPM1c is required to maintain the leukemic state. Here, we show that loss of NPM1c from the cytoplasm, either through nuclear relocalization or targeted degradation, results in immediate downregulation of homeobox (HOX) genes followed by differentiation.

SIGNOR-260138

P07478

P55085

1

cleavage

up-regulates activity

0.2

PAR1E and PAR2E (10 microM) were incubated in the presence of the different proteases | The enzymes were used at the following concentrations: 0.5 unit/mL thrombin, 2.5 nM trypsin, 20 nM plasmin, 20 nM cathepsin G, 20 nM elastase, 20 nM proteinase 3, and 2 units/mL calpain I and II|Protease-activated receptors (PARs) mediate cell activation after proteolytic cleavage of their extracellular amino terminus.|Mass spectrometry studies of PAR2E predicted activation of PAR2 by trypsin through cleavage at the Arg36-Ser37 site, no effect of thrombin, and inactivation of the receptor by plasmin, calpain and leukocyte elastase, cathepsin G, and proteinase 3

SIGNOR-263606

O43315

Q8TD84

2

binding

up-regulates activity

0.2

Our findings now further suggest that STAT3 and the adaptor protein SH2D2A interact with tyrosine‐containing motifs within the DSCAM/L1 ICDs. The SH2 domains of both STAT3 and SH2D2A are known to bind to phosphorylated tyrosine residues in the context of such motifs. Thus, the interactions between DSCAMs and SH2‐domain containing proteins seem to play a central and conserved role in Dscam signaling in the context of dynamic changes of tyrosine‐phosphorylation levels.

SIGNOR-264280

O43294

P06241

0

phosphorylation

up-regulates activity

0.34

Hic-5 is a CAKbeta-binding protein localized at focal adhesions. Here we show that overexpression of CAKbeta or Fyn, but not FAK, enhanced the tyrosine phosphorylation of coexpressed Hic-5 in COS-7 cells. The Y60F mutant of Hic-5 was not phosphorylated, and Hic-5 phosphorylated on tyrosine 60 was bound specifically to the SH2 domain of Csk. Specific phosphorylation of Hic-5 by CAKbeta and Fyn may activate a signaling pathway mediated by Hic-5.

SIGNOR-262875

Q8IXJ6

P18669

1

deacetylation

up-regulates activity

0.279

Here we report that PGAM is acetylated at lysine 100 (K100), an active site residue that is invariably conserved from bacteria, to yeast, plant, and mammals. K100 acetylation is detected in fly, mouse, and human cells and in multiple tissues and decreases PGAM2 activity. The cytosolic protein deacetylase sirtuin 2 (SIRT2) deacetylates and activates PGAM2.

SIGNOR-266517

Q13554

Q9UBS5

1

phosphorylation

down-regulates quantity by destabilization

0.2

ERK1/2 and CaMKIIβ mediated phosphorylation of GABAB1 at serine 867 (S867) and threonine 872 (T872). We found that, in addition to CaMKIIβ, also ERK1/2 is involved in the degradation pathway of GABAB receptors under physiological and ischemic conditions. In contrast to our previous view, CaMKIIβ does not appear to directly phosphorylate S867. Instead, the data support a mechanism in which CaMKIIβ activates ERK1/2, which then phosphorylates S867 and T872 in GABAB1.

SIGNOR-277851

P17542

Q99816

1

polyubiquitination

down-regulates quantity by destabilization

0.2

These data suggest that Tal mediates polyubiquitylation of the lysine residues in the VPS28-binding region of TSG101, leading to subsequent degradation of TSG101.

SIGNOR-271636

P31946

Q05655

0

phosphorylation

down-regulates

0.493

We provide a mechanism for these observations through the phosphorylation of 14-3-3 by ikk and pkc on serine residues ser132 and ser60, respectively, which interferes with its binding to ttp and hence the retention of ttp in the cytoplasm.

SIGNOR-138612

P53350

Q9H1A4

1

phosphorylation

up-regulates

0.524

Our analysis revealed an unexpected and unprecedented complexity of mitotic phosphorylation sites and suggests that other kinases than cdk1 and plk1 also contribute to apc phosphorylation.

SIGNOR-119881

P08754

O14843

2

binding

up-regulates activity

0.2

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

SIGNOR-256821

Q96RU7

P31749

2

binding

down-regulates activity

0.619

TRB3 expression is induced in liver under fasting conditions, and TRB3 disrupts insulin signaling by binding directly to Akt and blocking activation of the kinase.

SIGNOR-252644

Q9Y2W1

P23246

2

binding

down-regulates

0.436

Here we demonstrate that in resting tcells psf is directly phosphorylated by gsk3, thus promoting interaction of psf with trap150, which prevents psf from binding cd45 pre-mrna. Upon tcell activation, reduced gsk3 activity leads to reduced psf phosphorylation, releasing psf from trap150 and allowing it to bind cd45 splicing regulatory elements and repress exon inclusion.

SIGNOR-168441

P08754

P61073

2

binding

up-regulates activity

0.478

Using this model, we have reported that CXCL12 activates Gi1, Gi2, or Gi3 heterotrimeric G proteins in a concentration-dependent manner

SIGNOR-278104

P63096

O43306

2

binding

down-regulates activity

0.541

Types V and VI adenylyl cyclase are most sensitive to inhibition by Gnai1, Gnai2, and Gnai3

SIGNOR-278077

Q13127

O60741

1

transcriptional regulation

down-regulates quantity by repression

0.2

Levels of NRSF and its physical binding to the Hcn1 gene were augmented after SE, resulting in repression of HCN1 expression and HCN1-mediated currents (I(h) ), and reduced I(h) -dependent resonance in hippocampal CA1 pyramidal cell dendrites.

SIGNOR-268970

Q8TDI8

O75838

2

binding

up-regulates activity

0.334

Furthermore, we report that calcium and integrin-binding protein 2 binds to the components of the hair cell mechanotransduction complex, TMC1 and TMC2, and these interactions are disrupted by deafness-causing Cib2 mutations. We conclude that calcium and integrin-binding protein 2 is required for normal operation of the mechanotransducer channels and is involved in limiting the growth of transducing stereocilia.

SIGNOR-269664

P41968

P19086

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-257142

Q03164

Q01196

2

binding

up-regulates quantity by stabilization

0.568

Similar to CBFβ, we show that MLL binds to AML1 abrogating its proteasome-dependent degradation.Furthermore, we demonstrate that MLL binds to a region of AML1 (that is conserved in AML2 and AML3) and increases AML1 (AML2 and AML3) protein levels

SIGNOR-255707

Q16665

P13674

1

transcriptional regulation

up-regulates quantity by expression

0.314

Hypoxia upregulates P4HA1 expression in PDAC PDOs through HIF1α. Our results show that the treatment of PDO4 and PDO11 cells with 10 μmol/L of PX-478 for 24 hours reduced the levels of P4HA1 in hypoxia (Fig. 2F), suggesting P4HA1 expression in hypoxia is regulated by HIF1α expression.

SIGNOR-279840

Q9ULH7

P11831

2

binding

up-regulates activity

0.2

MKL2 binds to and activates SRF similar to myocardin and MKL1.

SIGNOR-237671

P09471

P50406

2

binding

up-regulates activity

0.252

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-257186

Q8NG66

P30304

1

phosphorylation

down-regulates

0.417

Nek11 regulates cdc25a degradation and the ir-induced g2/m checkpointincubation of wild-type cdc25a with nek11 led to a marked increase in phosphorylation of ser 82 and 88 as detected with the phosphospecific antibody recognizing these sites

SIGNOR-187867

P61278

P51608

0

post transcriptional regulation

up-regulates quantity by expression

0.297

MeCP2 binds to the promoter region of six target genes. ChIP with anti-MeCP2 antibody shows that MeCP2 binds to the promoter regions of activated targets Sst, Oprk1, Gamt, and Gprin1, and repressed targets Mef2c and A2bp1.

SIGNOR-264676

P53779

Q00535

0

phosphorylation

down-regulates activity

0.345

Here, we show that cdk5 directly phosphorylates c-Jun N-terminal kinase 3 (JNK3) on Thr131 and inhibits its kinase activity, leading to reduced c-Jun phosphorylation.

SIGNOR-250668

Q6JBY9

Q16644

0

phosphorylation

down-regulates activity

0.482

Human CapZIP was phosphorylated at Ser-179 and Ser-244 by MAPKAP-K2 (mitogen-activated protein kinase-activated protein kinase 2) or MAPKAP-K3 in vitro. In the present paper we have identified CapZIP as a protein that is phosphorylated exceptionally rapidly by several SAPKs in vitro (Figure 4), and which is expressed in muscles and immune cells. Both MAPKAP-K2 and MAPKAP-K3 phosphorylated CapZIP at Ser-179 in vitro. An important clue to the function of CapZIP and its phosphorylation came from the finding that it binds to the actin-capping protein CapZ (Figure 7A), and that cellular stresses trigger the dissociation of these two proteins (Figure 7B).Such an effect is presumably lost when CapZIP is phosphorylated and dissociates from CapZ.

SIGNOR-263082

O43186

Q02446

2

binding

up-regulates activity

0.388

Sp4 directly binds Crx. Sp4 and Sp1 produce much higher levels of transcriptional activation when co-transfected with Crx, they may additionally act by directly increasing the rate of transcriptional initiation by the general transcriptional apparatus through their activation domains.

SIGNOR-225333

Q9H300

Q15119

0

phosphorylation

up-regulates activity

0.2

As expected, knocking down PDK2 in HEK293 cells that overexpress PARL resulted in a significant increase in beta cleavage in comparison to the control cells.|Furthermore, we show that PDK2, a key regulator in metabolic plasticity, phosphorylates PARL and regulates \u03b2 cleavage.

SIGNOR-280018

P11831

P05231

1

null

up-regulates

0.281

Srf within myofibers modulates Il6 and Cox2/Il4 expressions and, therefore, exerts a paracrine control of satellite cell proliferation and fusion, respectively, which in turn support skeletal muscle hypertrophy.

SIGNOR-255966

F7VJQ1

Q00535

0

phosphorylation

up-regulates quantity

0.332

Cdk5 phosphorylated PrP induces the aggregation of non phosphorylated PrP.|Together, these results indicate that S43 is a major Cdk5 phosphorylation site in PrP.

SIGNOR-278920

P08581

P40763

1

phosphorylation

up-regulates activity

0.706

It has been reported that c-Met can activate STAT3 at the endosome and phosphorylated STAT3 induced by c-Met is colocalized with EEA1, an early endosome marker.

SIGNOR-280041

Q13535

P16220

1

phosphorylation

down-regulates

0.347

Atm phosphorylated creb in vitro and in vivo in response to ionizing radiation (ir) and h(2)o(2) on a stress-inducible domain. Ir-induced phosphorylation of creb correlated with a decrease in creb transactivation potential and reduced interaction between creb and its transcriptional coactivator, creb-binding protein (cbp). A creb mutant containing ala substitutions at atm phosphorylation sites displayed enhanced transactivation potentialit is, therefore, likely that atm and atr regulate creb phosphorylation collectively in response to stress stimuli.

SIGNOR-124060