GleghornLab/Signor_processed · Datasets at Hugging Face

IdA stringlengths 6 21	IdB stringlengths 6 21	mechanism stringclasses 40 values	effect stringclasses 10 values	score float64 0.1 0.99 ⌀	sentence stringlengths 10 1.63k ⌀	signor_id stringlengths 12 14
Q9ULZ2	Q14289	phosphorylation	up-regulates activity	0.352	In 293 cells expressing recombinant BRDG1 and various PTKs, Tec and Pyk2, but not Btk, Bmx, Lyn, Syk, or c-Abl, induced marked phosphorylation of BRDG1 on tyrosine residues. BRDG1 was also phosphorylated by Tec directly in vitro. Furthermore, BRDG1 was shown to participate in a positive feedback loop by increasing the activity of Tec. BRDG1 thus appears to function as a docking protein acting downstream of Tec in BCR signaling.	SIGNOR-261818
Q93045	P27361	phosphorylation	down-regulates activity	0.352	SCG10, a growth cone-enriched MT-destabilizing protein, has been recently characterized as an in vitro substrate for various serine/threonine kinases including PKA, MAP kinase, and CDK (19). We have found that SCG10 is phosphorylated in vivo in developing rat brain.\| The sites for MAP kinase phosphorylation were identified as Ser-62 and Ser-73 of SCG10\|By expressing a series of phosphorylation site mutants, we showed that the MT-destabilizing effect of SCG10 could be modulated. While the nonphosphorylatable mutant showed higher activity than the wild-type protein, the activity of the mutant in which phosphorylation on all four sites was mimicked by an aspartate residue was greatly reduced. These data suggest that the nonphosphorylated state of SCG10 represents the most active form of the protein.	SIGNOR-249115
P06748	Q13315	phosphorylation	up-regulates activity	0.352	In addition to Serine 125, ATM may also phosphorylate other sites on NPM.	SIGNOR-280182
Q9UHD2	O75688	dephosphorylation	down-regulates activity	0.352	PPM1B dephosphorylates TBK1 in vivo and in vitro.\|These results demonstrate that PPM1B inhibits TBK1 mediated antiviral signaling by directly dephosphorylating TBK1 at Ser172.	SIGNOR-276985
P47712	O75582	phosphorylation	up-regulates activity	0.352	Serine 727 phosphorylation and activation of cytosolic phospholipase A2 by MNK1-related protein kinases.	SIGNOR-249051
Q8TDI7	O75838	binding	up-regulates activity	0.352	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-269665
Q9UQL6	Q05655	phosphorylation	down-regulates activity	0.352	In this report, we show that VEGF stimulates PKD-dependent phosphorylation of HDAC5 at Ser259/498residues in ECs, which leads to HDAC5 nuclear exclusion and myocyte enhancer factor-2 (MEF2) transcriptional activation.	SIGNOR-260875
O00401	P20929	binding	up-regulates	0.352	Igf1-akt signaling, by inhibiting gsk3b, allows the interaction of n-wasp with the unphosphorylated nebulin;the consequent recruitment of n-wasp to the z-disk promotes actin nucleation and elongation of actin filaments.	SIGNOR-175671
Q9HCE7	P31749	phosphorylation	up-regulates activity	0.352	Furthermore, phosphorylation of Smurf1 by Akt1 was carried out specifically on the T145 residue, as mutation of this site abolished recognition of Smurf1 by the Akt1 phosphorylation motif antibody (Figure 5D).\|We also identified that Smurf1 itself is targeted for phosphorylation by Akt1 and Akt2, regulating its stability.	SIGNOR-279778
P41180	P17252	phosphorylation	down-regulates	0.351	Casr(t888) is a protein kinase c (pkc) phosphorylation site in the receptor's intracellular domain that has previously been identified as a critical negative regulator of casr downstream signaling in vitro, thus, casr(t888) represents a functionally important, inhibitory phosphorylation site that contributes to the control of pth secretion.	SIGNOR-170334
Q05586	P05129	phosphorylation	up-regulates activity	0.351	Serines 890 and 896 of the NMDA receptor subunit NR1 are differentially phosphorylated by protein kinase C isoforms. The results show that PKC alpha phosphorylates preferentially S896 and PKC gamma preferentially S890.	SIGNOR-263176
Q13586	P28482	phosphorylation	up-regulates	0.351	The netrin-2-mediated nfatc3 activation was coincident with robust interactions between cdo and stim1 in myoblasts and the erk-mediated stim1 phosphorylation at serine 575	SIGNOR-192788
Q96P20	Q9UKC9	binding	down-regulates quantity by destabilization	0.351	LPS exposure reduces the ubiquitin-mediated proteasomal processing of NALP3 by inducing levels of an E3 ligase component, FBXO3, which targets FBXL2. The latter is an endogenous mediator of NALP3 degradation. FBXL2 recognizes Trp-73 within NALP3 for interaction and targets Lys-689 within NALP3 for ubiquitin ligation and degradation.	SIGNOR-272432
P10586	Q96NI6	binding	up-regulates activity	0.351	SALM5 trans-synaptically interacts with LAR-RPTPs in a splicing-dependent manner to regulate synapse development. we identified LAR-RPTPs as novel ligands of SALM5 that mediates SALM5-dependent presynaptic differentiation in a splicing-dependent manner. Our data indicate that SALM5 interacts with all three known LAR-RPTPs—LAR, PTPδ, and PTPσ (Fig. 1).	SIGNOR-264087
Q8IZL8	P11802	phosphorylation	up-regulates	0.351	Using site-directed mutagenesis and in vitro kinase assays, we identified ser(477) and ser(991) of pelp1 as cdk phosphorylation sites. we identified pelp1 as a novel substrate of cdks and found that cdk phosphorylation is important for the proper function of pelp1 in modulating hormone-driven cell cycle progression and also for optimal e2f transactivation function.	SIGNOR-167770
P04637	P51948	ubiquitination	down-regulates quantity by destabilization	0.351	Collectively, these results indicate that MNAT1 increases p53 ubiquitination, thus promoting its proteasomal degradation.\|These suggest that MNAT1 decreases p53 expression by the proteasome.	SIGNOR-278831
P27987	P17612	phosphorylation	down-regulates activity	0.351	Two isoforms of the inositol 1,4,5-trisphosphate 3-kinase have been identified, the A form and the B form. phosphorylation of isoform A by the cyclic AMP-dependent protein kinase increased activity 1.5-fold, whereas phosphorylation of isoform B decreased activity by 45%. major phosphorylation sites in the protein are Ser119 for PKA. Ser119 in the A isoform is conserved in the B isoform as Ser328	SIGNOR-249995
P23396	P27361	phosphorylation	up-regulates	0.351	Erk phosphorylates threonine 42 residue of ribosomal protein s3.	SIGNOR-137175
P55210	Q13177	phosphorylation	down-regulates	0.351	Pak2 can bind with caspase-7 and phosphorylate caspase-7 at the ser-30, thr-173, and ser-239 sites. Functionally, the phosphorylation of caspase-7 decreases its activity, thereby inhibiting cellular apoptosis.	SIGNOR-173655
Q9H2G9	O95271	ADP-ribosylation	down-regulates quantity by destabilization	0.351	Here, we identify RNF146, a RING-domain E3 ubiquitin ligase, as a positive regulator of Wnt signalling. RNF146 promotes Wnt signalling by mediating tankyrase-dependent degradation of axin. Mechanistically, RNF146 directly interacts with poly(ADP-ribose) through its WWE domain, and promotes degradation of PARsylated proteins. Using proteomics approaches, we have identified BLZF1 and CASC3 as further substrates targeted by tankyrase and RNF146 for degradation.	SIGNOR-263385
O95831	P04637	transcriptional regulation	up-regulates quantity by expression	0.351	P53 regulates basal expression of AIF and SCO2 and facilitates oxidative phosphorylation. The expression of GLUT1, GLUT4, and HK2 is negatively regulated by p53, whereas TIGAR expression is induced by p53. The net result of p53-mediated regulation of these glycolytic enzymes is the suppression of glycolysis. In addition, p53 directly binds and inhibits G6PD activity and downregulates the pentose phosphate pathway.	SIGNOR-267462
Q01094	Q16531	binding	up-regulates	0.351	We show that ddb, a putative dna repair protein, associates with the activation domain of e2f1 / expression of ddb specifically stimulated e2f1-activated transcription	SIGNOR-54096
Q08050	P45974	deubiquitination	up-regulates quantity by stabilization	0.351	Wnt signaling activation inhibits FoxM1 phosphorylation by GSK3-Axin complex and leads to interaction between FoxM1 and deubiquitinating enzyme USP5, thereby deubiquitination and stabilization of FoxM1.	SIGNOR-277210
P50539	P23443	phosphorylation	down-regulates activity	0.351	Phosphorylation of Mxi1 by S6K1 at S160 site promotes its binding to beta-Trcp and ubiquitin mediated degradation.\|The above findings demonstrate that S6K1 and beta-Trcp negatively regulates the stability of Mxi1 through ubiquitin proteasome pathway.	SIGNOR-278231
P37840	P53350	phosphorylation	down-regulates activity	0.351	Polo-like kinase (plk) family (plk1, plk2, and plk3) phosphorylate alpha-syn and beta-syn specifically at ser-129 and ser-118, respectively. Polo-like kinase 2 (plk2) phosphorylates alpha-synuclein at serine 129 in central nervous system. The membrane association of pd-linked mutant alpha -synuclein, but not wild-type -synuclein, was increased by serine 129 phosphorylation.	SIGNOR-189045
P12931	Q8N2C7	binding	up-regulates activity	0.351	UNC80 is a protein that is associated with the NALCN Na(+) leak cation channel, and is required for the activation of this channel by the neuropeptide substance P through GPCRs in a G-protein-independent fashion. Here, we show that UNC80 binds Src kinases and recruits Src into the channel complex.	SIGNOR-265179
P04637	Q9HCM9	ubiquitination	down-regulates quantity by destabilization	0.351	Furthermore, we show here that the Trim39 can directly bind and ubiquitylate p53 in vitro and in vivo, leading to p53 degradation.	SIGNOR-272020
Q02548	P28482	phosphorylation	down-regulates activity	0.351	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-269087
O95140	P45984	phosphorylation	down-regulates	0.351	Jnk phosphorylation of mitofusin 2 in response to cellular stress leads to recruitment of the ubiquitin ligase (e3) huwe1/mule/arf-bp1/hecth9/e3histone/lasu1 to mitofusin 2, with the bh3 domain of huwe1 implicated in this interaction. This results in ubiquitin-mediated proteasomal degradation of mitofusin 2these data establish that mfn2 is phosphorylated on ser27 in response to a variety of cellular stresses and implicate jnk in this process	SIGNOR-198054
P01236	P31270	transcriptional regulation	up-regulates quantity by expression	0.351	HoxA-11 enhanced upregulation of PRL only in differentiated cells.	SIGNOR-261630
Q99856	P78347	binding	up-regulates activity	0.35	In this work, we show that TFII-I directly interacts with human Bright through amino acids in Bright's protein interaction domain and that specific tyrosine residues of TFII-I are essential for Bright-induced activity of an immunoglobulin reporter gene. Moreover, inhibition of TFII-I function in a B-cell line resulted in decreased heavy-chain transcript levels.	SIGNOR-268533
P15311	Q9H270	binding	up-regulates activity	0.35	The interaction between the full-length Vps11 and ezrin was confirmed by immunoprecipitation and GST-pull down. ERM proteins and the HOPS complex are required for the transition from early to late endosomes	SIGNOR-261311
P23528	Q13418	phosphorylation	down-regulates	0.35	Actin (de)polymerization is regulated by cofilin, the ser(3) phosphorylation (ps(3)cofilin) of which inhibits its actin-severing activity. To determine how ilk regulates ps(3)cofilin, we examined the effects of ilk on ps(3)cofilin using normal rie1 cells.	SIGNOR-160756
P19086	P47736	binding	down-regulates activity	0.35	Biochemical analysis using purified recombinant proteins revealed that the physical interaction between Gaz and Rap1GAP blocks the ability of RGSs (regulators of G protein signaling) to stimulate GTP hydrolysis of the a subunit, and also attenuates the ability of activated Gaz to inhibit adenylyl cyclase.	SIGNOR-278053
Q06187	P50148	binding	up-regulates activity	0.35	AlF− 4-activated Gaq-GDP increased Btk activity as expected, whereas AlF− 4 alone had no stimulatory effect (Table 1), so we conclude that Gaq directly stimulates Btk kinase activity	SIGNOR-278083
P20042	P68400	phosphorylation	up-regulates	0.35	The n-terminal domain of the human eif2beta subunit and the ck2 phosphorylation sites are required for its function. These results suggest that ser2 and ser67 contribute to the important role of the n-terminal region of eif2beta for its function in mammals.	SIGNOR-140994
P10914	Q14164	phosphorylation	down-regulates activity	0.35	We demonstrated that IKK-ε phosphorylated the transcription factor IFN regulatory factor 1 (IRF-1) at amino acid (aa) 215/219/221 in primary CD4(+) T cells and blocked its transcriptional activity.	SIGNOR-276480
Q99958	Q00535	phosphorylation	up-regulates activity	0.35	Cdk5 phosphorylates Foxc2 and activates Foxc2 dependent transcription.	SIGNOR-279156
Q14344	Q9H1C0	binding	up-regulates activity	0.35	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-257284
P08235	P27361	phosphorylation	down-regulates quantity by destabilization	0.35	Taken together, these data suggest that ERK1/2 directly phosphorylates the MR on several serine residues present in its NTD, that the upward shift of MR is mainly due to receptor phosphorylation, and finally that these sites represent the major aldosterone-inducible targets for MR phosphorylation.MR phosphorylation limits the transcriptional activity.Taken together, these results provide evidence that MR phosphorylation plays a role in aldosterone-mediated ubiquitylation and degradation.	SIGNOR-276102
P11511	P12931	phosphorylation	up-regulates	0.35	Phosphorylation of the 361-tyrosine residue is crucial in the up-regulation of aromatase activity. c-src protein directly phosphorylates aromatase on tyrosine 361.	SIGNOR-186284
P01106	Q8TEL6	binding	down-regulates quantity by destabilization	0.35	We characterize a new Myc-interacting factor, TRPC4AP (transient receptor potential cation channel, subfamily C, member 4-associated protein)/TRUSS (tumor necrosis factor receptor-associated ubiquitous scaffolding and signaling protein), which is the receptor for a DDB1 (damage-specific DNA-binding protein 1)-CUL4 (Cullin 4) E3 ligase complex for selective Myc degradation through the proteasome. TRPC4AP/TRUSS binds specifically to the Myc C terminus and promotes its ubiquitination and destruction through the recognition of evolutionarily conserved domains in the Myc N terminus.	SIGNOR-271963
P11940	Q9UHC7	ubiquitination	up-regulates activity	0.35	We show that MKRN1 directly binds to the cytoplasmic poly(A)-binding protein (PABPC1) and associates with polysomes. MKRN1 is positioned upstream of poly(A) tails in mRNAs in a PABPC1-dependent manner. Ubiquitin remnant profiling and in vitro ubiquitylation assays uncover PABPC1 and ribosomal protein RPS10 as direct ubiquitylation substrates of MKRN1.Our data show that MKRN1 associates with polysomes and ubiquitylates RPS10, indicating a role in translational control. We hypothesize that ribosomes encountering the MKRN1-PABPC1 complex are stalled, possibly via ubiquitylation of RPS10 on K107 and other MKRN1 substrates.	SIGNOR-272215
Q13635	Q9Y625	binding	up-regulates activity	0.35	Based on results from in vitro experiments, we had previously proposed that GPC6 stimulates Hh signaling by interacting with Hh and Patched1 (Ptc1), and facilitating/stabilizing their interaction.	SIGNOR-264031
Q96PD2	P06241	phosphorylation	up-regulates activity	0.35	Mutagenesis analysis of ESDN's seven intracellular tyrosines in YxxP motifs found several contribute to the binding of ESDN to the SH2 domains of both CrkCT10 regulator of kinase Crk-Like (CrkL) and a representative SFK Fyn. Quantitative mass spectrometry showed that at least three of these (Y565, Y621 and Y750), as well as non-YxxP Y715, are reversibly phosphorylated. SFK activity was shown to be sufficient, but not required for the interaction between ESDN and the CrkL-SH2 domain. Finally, antibody-mediated ESDN clustering induces ESDN tyrosine phosphorylation and CrkL-SH2 binding.	SIGNOR-273946
P56524	P67775	dephosphorylation	up-regulates	0.35	Different signal-regulated serine/threonine kinases phosphorylate class ii histone deacetylases (hdacs) to promote nuclear export, cytosolic accumulation, and activation of gene transcriptionhere we show that hdac4 forms a complex with the pp2a holoenzyme c alpha, a alpha, b/pr55 alpha. In vitro and in vivo binding studies demonstrate that the n-terminus of hdac4 interacts with the catalytic subunit of pp2a. Hdac4 is dephosphorylated by pp2a	SIGNOR-159492
P56704	O75487	binding	up-regulates	0.35	Gpc4 bound to wnt3a and wnt5a which activate the beta-catenin-dependent and -independent pathways, respectively, and colocalized with wnts on the cell surface. Expression of gpc4 enhanced the wnt3a-dependent beta-catenin pathway and the wnt5a-dependent beta-catenin-independent pathway, and knockdown of gpc4 suppressed both pathways	SIGNOR-195749
P35659	P68400	phosphorylation	up-regulates	0.35	Dek is phosphorylated by the protein kinase ck2 in vitro and in vivo on ser32	SIGNOR-125912
P50549	Q15418	phosphorylation	up-regulates activity	0.35	Here we describe that the 90-kDa ribosomal S6 kinase 1 (RSK1), a protein kinase downstream of the extracellular signal-regulated kinase (ERK) subclass of MAPKs, binds to ER81, phosphorylates it, and enhances ER81-dependent transcription. Two in vivo RSK1 phosphorylation sites within ER81, Ser(191) and Ser(216), were identified, whose mutation to alanine reduces ER81 activity upon ERK-MAPK stimulation.	SIGNOR-249163
Q13224	P51608	transcriptional regulation	down-regulates quantity by repression	0.35	The interaction of MeCP2 with the 2BI3 and 2BI5 sites was strikingly reduced in neurons maintained in the presence of TTX (Fig. 2C). This result is consistent with the classical view of MeCP2 as a general transcriptional repressor, in that the reduced association leads to increased expression of NR2B.	SIGNOR-264685
O94925	P05412	transcriptional regulation	up-regulates quantity by expression	0.35	The transcription factor c-Jun can directly bind to the GLS gene promoter and enhance expression	SIGNOR-268035
P63092	Q14832	binding	up-regulates activity	0.35	MGluRs are members of the G-protein-coupled receptor (GPCR) superfamily, the most abundant receptor gene family in the human genome. GPCRs are membrane-bound proteins that are activated by extracellular ligands such as light, peptides, and neurotransmitters, and transduce intracellular signals via interactions with G proteins. The resulting change in conformation of the GPCR induced by ligand binding activates the G protein, which is composed of a heterotrimeric complex of α, β, and γ subunits.	SIGNOR-264083
Q9NYJ7	Q86YT6	ubiquitination	up-regulates activity	0.35	Mib physically interacts with Delta and promotes its ubiquitination and internalization [66], which have been shown to up-regulate Notch activity.	SIGNOR-209672
Q9UBN4	Q96J02	ubiquitination	down-regulates activity	0.35	Ubiquitination of TRPV4 is dramatically increased by the HECT (homologous to E6-AP carboxyl terminus)-family ubiquitin ligase AIP4 without inducing degradation of this channel. Instead, AIP4 promotes the endocytosis of TRPV4 and decreases its amount at the plasma membrane.	SIGNOR-272624
P61586	Q13829	binding	down-regulates quantity	0.35	BACURDs form ubiquitin ligase complexes, which selectively ubiquitinate RhoA, with Cul3. Our studies reveal a previously unknown mechanism for controlling RhoA degradation and regulating RhoA function in various biological contexts, which involves a Cul3/BACURD ubiquitin ligase complex.	SIGNOR-264235
P17752	P17612	phosphorylation	up-regulates activity	0.35	The activation of tryptophan hydroxylase by protein kinase A is mediated by the phosphorylation of serine-58 within the regulatory domain of the enzyme.	SIGNOR-250062
Q8TEW0	O14965	phosphorylation	up-regulates	0.35	Aurora a interacts directly with the atypical protein kinase c binding domain of par3 and phosphorylates it at serine 962. The phosphorylation of par3 at serine 962 contributes to its function in the establishment of neuronal polarity.	SIGNOR-188398
Q92886	Q13164	phosphorylation	up-regulates activity	0.35	Activation of ERK5 potentiates while inhibition of ERK5 attenuates Neurog1 stimulated neurogenesis.\|ERK5 directly phosphorylated Neurog1 in vitro and modulated the transcriptional and pro-neural activity of Neurog1 in cortical progenitors.	SIGNOR-278364
Q8N137	P51955	phosphorylation	down-regulates activity	0.35	The opposite outcomes in NEK2- and centrobin-depleted cells suggest that NEK2 antagonizes biological functions of centrobin.\|These results suggest that NEK2 phosphorylates specific sites of centrobin, which are distinct from the PLK1 phosphorylation sites.	SIGNOR-279545
O60885	Q96QE3	binding	up-regulates	0.35	ATAD5 Interacts with BRD4 through a Conserved BET Protein-Binding Domain. BRD4-ATAD5 binds to acetyl-histones in nascent chromatin. BRD4 release from chromatin correlates with PCNA unloading. Disruption of the interaction between BRD4 and acetyl-histones or between BRD4 and ATAD5 reduces the PCNA amount on chromatin.	SIGNOR-266412
Q06830	P06493	phosphorylation	down-regulates	0.35	Peroxiredoxin (prx) i is a member of the peroxiredoxin family of peroxidases and contains a consensus site (thr(90)-pro-lys-lys) for phosphorylation by cyclin-dependent kinases (cdks). This protein has now been shown to be phosphorylated specifically on thr(90) by several cdks, including cdc2, in vitro. Phosphorylation of prx i on thr(90) reduced the peroxidase activity of this protein by 80%.	SIGNOR-87097
P02461	P03956	cleavage	down-regulates quantity by destabilization	0.35	In vitro, MMP1 initiates degradation of native fibrillar collagens, crucial components of vertebrate extracellular matrix (ECM), by cleaving the peptide bond between Gly775–Ile776 or Gly775–Lys776 in native type I, II or III collagen molecules3,4.	SIGNOR-272339
Q9HBA0	P06241	phosphorylation	up-regulates activity	0.35	ROS could be detected by Fyn, which is required to activate TRPV4 in a redox-sensitive manner.\|The Ca 2+ response to H 2 O 2 required the basal phosphorylation of TRPV4 by the Src kinase Fyn, which may serve as the redox sensor responsible for TRPV4 activation (Figure 2 ) [220] , and was able to increase barrier permeability [219] .	SIGNOR-279991
P11387	P06493	phosphorylation	up-regulates activity	0.349	In vitro kinase assays demonstrated that Ser(10) can be phosphorylated by casein kinase II, Ser(21) can be phosphorylated by protein kinase Calpha, and Ser(112) and Ser(394) can be phosphorylated by Cdk1.Collectively these results indicate that topo I is phosphorylated during mitosis at multiple sites, one of which enhances DNA relaxation activity in vitro and interaction with DNA in cells.	SIGNOR-276157
P10415	P17252	phosphorylation	up-regulates	0.349	Purified pkca can efficiently and directly phosphorylate bcl2 at serine 70	SIGNOR-60120
P32243	P48436	binding	up-regulates activity	0.349	BEST1 promoter activity was increased by SOX9 overexpression and decreased by siRNA-mediated SOX9 knockdown. SOX9 physically interacted with MITF and OTX2 and orchestrated synergistic activation of the BEST1 promoter with the paired SOX site playing essential roles.	SIGNOR-255184
Q14103	P17612	phosphorylation	up-regulates	0.349	Protein kinase a enhances, whereas glycogen synthase kinase-3 beta inhibits, the activity of the exon 2-encoded transactivator domain of heterogeneous nuclear ribonucleoprotein d in a hierarchical fashion.	SIGNOR-116144
Q96KS0	Q969H0	ubiquitination	down-regulates quantity by destabilization	0.349	Mechanistically, we further show that FBW7, an E3 ligase complex component that is frequently downregulated in TNBC, negatively regulates EglN2 protein stability.	SIGNOR-261997
O15553	Q16513	phosphorylation	down-regulates activity	0.349	PKNs bind to human pyrin and phosphorylate S208 and S242. Pyrin forms an inflammasome when mutant or in response to bacterial modification of the GTPase RhoA. We found that RhoA activated the serine-threonine kinases PKN1 and PKN2 that bind and phosphorylate pyrin. Phosphorylated pyrin bound to 14-3-3 proteins, regulatory proteins that in turn blocked the pyrin inflammasome.	SIGNOR-275464
Q7KZI7	P49841	phosphorylation	down-regulates activity	0.349	MARK family kinases can be activated by phosphorylation of a conserved threonine (Thr-208 in MARK2), and inactivated by phosphorylation of a serine (Ser-212), both in the activation loop of the catalytic domain. Activation is achieved by the kinases MARKK/TAO1 or LKB1, although the inactivating kinase was unknown. We show here that GSK3beta serves the role of the inhibitory kinase.	SIGNOR-276163
Q00613	Q04759	phosphorylation	up-regulates	0.349	At the same time, ea causes pkc?-Mediated phosphorylation and activation of the transcription factor heat shock factor 1, an inducer of glucose dependence.	SIGNOR-200576
O14737	O14829	dephosphorylation	down-regulates quantity by destabilization	0.349	Here, we report that the serine/threonine phosphatase PPEF-1 interacts with and dephosphorylates PDCD5 at Ser 119, which leads to PDCD5 destabilization.\|These results demonstrate that PPEF-1 reduces PDCD5 stability via PDCD5 dephosphorylation.	SIGNOR-277008
P16144	O14713	binding	down-regulates activity	0.349	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-257658
Q01726	Q8TCY5	binding	down-regulates activity	0.349	We report that MRAP and MRAP2 can interact with all 5 MCRs. This interaction results in MC2R surface expression and signaling. In contrast, MRAP and MRAP2 can reduce MC1R, MC3R, MC4R, and MC5R responsiveness to [Nle4,D-Phe7]alpha-melanocyte-stimulating hormone (NDP-MSH). MRAP and MRAP2 can reduce the surface expression of MC4R and also the signaling of this receptor. we observed a significant decrease in the cell-surface expression of MC4R and MC5R in the presence of MRAP and MRAP2. It is interesting that MRAP and MRAP2 have opposite effects in the modulation of different MCR family members.	SIGNOR-252364
P46695	Q00987	ubiquitination	down-regulates quantity by destabilization	0.349	FHL2 stimulates MDM2 mediated ubiquitination of IER3 by forming a ternary complex.\|Scaffold protein FHL2 facilitates MDM2 mediated degradation of IER3 to regulate proliferation of cervical cancer cells.	SIGNOR-278824
Q13444	P06239	phosphorylation	up-regulates	0.349	Hck, and to a lesser extent lck, phosphorylated the adam15. Deletion and point mutation analysis of the adam15 cytoplasmic domain confirmed the importance of the proline-rich motifs for grb2 and lck binding and indicated the regulatory nature of tyr(715) and tyr(735). These data demonstrate selective, phosphorylation-dependent interactions of adam15 with src family ptks and grb2, which highlight the potential for integration of adam functions and cellular signaling.	SIGNOR-112931
P63096	P28223	binding	up-regulates activity	0.349	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-256742
P61289	O96017	phosphorylation	up-regulates activity	0.349	REGγ interacts with DBC1 and is phosphorylated by Chk2.	SIGNOR-273611
O60674	Q5VWQ8	binding	down-regulates activity	0.349	In vascular smooth muscle cells (VSMCs) treated with IFN-γ, DAB2IP directly binds to JAK2 and inhibits its kinase activity, limiting JAK-dependent STAT1/3 and PI3K–AKT phosphorylation and activation	SIGNOR-254760
O00429	Q9UM11	ubiquitination	down-regulates quantity	0.349	Here we demonstrate that changes in mitochondrial dynamics as cells exit mitosis are driven in part through ubiquitylation of Drp1 catalyzed by the APC/Ccdh1 (anaphase-promoting complex/cyclosome and its coactivator (Cdh1) E3 ubiquiting ligase complex	SIGNOR-274127
P09471	P08172	binding	up-regulates activity	0.349	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-256964
P53350	P49137	phosphorylation	up-regulates	0.349	Here, we have identified mk2 as a major plk1 kinase toward ser326, whose phosphorylation is critical to recruit ?-Tubulin to centrosomes and subsequent establishment of functional bipolar spindles. To our knowledge, this is the first direct evidence to demonstrate that the essential function of plk1 in centrosome maturation and bipolar spindle formation is controlled by its upstream kinase.	SIGNOR-179968
P78352	Q05086	ubiquitination	down-regulates quantity by destabilization	0.349	E6-induced degradation of DLG4 depends on E6AP in vivo. Our findings as a whole indicate that E6AP is involved in E6-mediated ubiquitination and degradation of DLG4 both in vivo and in vitro.	SIGNOR-271397
Q99607	Q13315	phosphorylation	down-regulates activity	0.349	Elf4 is phosphorylated by Atm after gamma irradiation, leading to its degradation.\|Thus, Atm promotes Elf4 protein degradation after gamma irradiation via phosphorylation at these sites.	SIGNOR-278466
P01106	Q8N1E6	ubiquitination	down-regulates quantity by destabilization	0.349	In this study, we demonstrate that the deubiquitinase USP13 stabilizes c-Myc by antagonizing FBXL14-mediated ubiquitination to maintain GSC self-renewal and tumorigenic potential. USP13 was preferentially expressed in GSCs, and its depletion potently inhibited GSC proliferation and tumor growth by promoting c-Myc ubiquitination and degradation.	SIGNOR-274125
P01112	Q7Z5G4	palmitoylation	up-regulates activity	0.349	Covalent lipid modifications mediate the membrane attachment and biological activity of Ras proteins. All Ras isoforms are farnesylated and carboxyl-methylated at the terminal cysteine; H-Ras and N-Ras are further modified by palmitoylation. Here we report that H- and N-Ras are palmitoylated by a human protein palmitoyltransferase encoded by the ZDHHC9 and GCP16 genes. DHHC9 is an integral membrane protein that contains a DHHC cysteine-rich domain. GCP16 encodes a Golgi-localized membrane protein.	SIGNOR-261351
P17600	Q13153	phosphorylation	up-regulates activity	0.349	Synapsin I is phosphorylated at Ser603 by p21-activated kinases. the Ser603 residue must be one of the pivotal sites for the release	SIGNOR-250235
Q16665	Q9H4B4	phosphorylation	down-regulates	0.348	Polo-like kinase 3 functions as a tumor suppressor and is a negative regulator of hypoxia-inducible factor-1 alpha under hypoxic conditionsplk3 can potentially inhibit hif-1_ by physical interaction and direct phosphorylation	SIGNOR-178743
Q00613	P19784	phosphorylation	up-regulates	0.348	Transcriptional activity and dna binding of heat shock factor-1 involve phosphorylation on threonine 142 by ck2.As hsf1 is activated by heat shock simultaneously with the nuclear translocation of the protein kinase ck2, we have investigated the role of ck2 in hsf1 activatio	SIGNOR-99606
O95863	P68400	phosphorylation	up-regulates quantity by stabilization	0.348	Serines 11 and 92 participate in the control of snail1 stability and positively regulate snail1 repressive function and its interaction with msin3a corepressor. Furthermore, serines 11 and 92 are required for snail1-mediated emt and cell viability, respectively. Pka and ck2 have been characterized as the main kinases responsible for in vitro snail1 phosphorylation at serine 11 and 92, respectively.	SIGNOR-161771
P41594	Q05655	phosphorylation	up-regulates activity	0.348	Thus, we showed that it is phosphorylation of Ser-839, not Thr-840, that is absolutely required for the unique Ca2+ oscillations produced by mGluR5 activation. The Thr-840 residue is important only in that it is permissive for the PKC-dependent phosphorylation of Ser-839.	SIGNOR-249287
Q9Y6R1	Q9UEW8	phosphorylation	down-regulates activity	0.348	SPAK phosphorylates the transporters to reduce their surface expression and thus their activity and consequently inhibits ductal secretion to stabilize the resting state. PP1 reverses the effect of SPAK. Molecular analysis revealed that the WNK kinases acted as scaffolds to recruit SPAK, which phosphorylated CFTR and NBCe1-B, reducing their cell surface expression.	SIGNOR-263133
Q16625	Q96J02	ubiquitination	down-regulates quantity by destabilization	0.348	Two mechanisms regarding junction protein turnover were illustrated in this process, that is, the Itch-induced occludin ubiquitination and proteasome degradation, and the caveolae-dependent endocytosis of junction proteins (JAM-A, N-cadherin, and \u03b2 -catenin), both of which led to the instability of junction apparatus between adjacent SCs and a subsequent damaged BTB.	SIGNOR-278756
O15297	P06493	phosphorylation	down-regulates quantity by destabilization	0.348	Phosphorylation of multiple residues in the catalytic domain of PPM1D during mitosis, including Ser40 by Cyclin-dependent kinase 1 (CDK1), leads to ubiquitination of PPM1D and subsequent proteasomal degradation by Adenomatous polyposis coli (APC) and cell-division cycle protein 20 (CDC20)	SIGNOR-275489
P30307	P11309	phosphorylation	up-regulates activity	0.348	First, Pim-1 activates the Cdc25C phosphatase directly through phosphorylation, very probably at the N-terminal part of the protein.\|We find that phosphorylation by Pim-1 enhances the phosphatase activity of Cdc25C and in transfected cells that are arrested in G2/M by bleomycin, Pim-1 can enhance progression into G1.	SIGNOR-278298
Q9NPF5	Q7Z553	binding	up-regulates quantity by stabilization	0.348	The anti-tumorigenic effect of MDGA2 was mediated through direct stabilising of DNA methyltransferase 1 associated protein 1 (DMAP1), which played a tumour suppressive role in gastric cancer. MDGA2 expression and MG132 treatment increased the level of DMAP1, suggesting that the MDGA2–DMAP1 interaction stabilises DMAP1 by inhibiting its ubiquitin-mediated degradation.	SIGNOR-264240
Q99828	P60763	binding	up-regulates activity	0.348	We here report that CIB, a protein that binds to the alpha(IIb)beta(3) fibrinogen receptor, interacts exclusively with activated (V12) Rac3 but not Rac1 or Rac2. Binding of V12Rac3 to CIB was mediated by the C-terminal end of Rac3 and by Rac3 membrane localization	SIGNOR-269060
Q07955	O43187	phosphorylation	down-regulates activity	0.348	IRAK2 phosphorylates SRSF1 and thereby reduces SRSF1 binding to the target mRNAs.	SIGNOR-278406
P35590	Q02763	phosphorylation	up-regulates activity	0.348	Thus, Tie2 was able to induce Tie1 phosphorylation.\|When cotransfected, Tie2 formed heteromeric complexes with Tie1, enhanced Tie1 activation, and induced phosphorylation of a kinase-inactive Tie1 in a ligand-dependent manner.	SIGNOR-279769
P42224	P22455	phosphorylation	up-regulates activity	0.348	Activation of Stat1 and Stat3 by FGFR derivatives. Lysates of 293T cells transfected as indicated were analysed by Western blotting using Phospho-Stat1 (Y701) antisera (top) or Stat1 antisera (bottom). (b) The same lysates in (a) were re-examined for phosphorylated Stat3 by Western blotting with Phospho-Stat3 (Y705) (top). all three FGFR family members examined here are able to lead to Stat activation. Expression of the 'TDII-like' derivatives of FGFR1, FGFR3, and FGFR4, as well as myrR1-WT, led to phosphorylation of both Stat1 and Stat3.	SIGNOR-251141

Q9ULZ2

Q14289

0

phosphorylation

up-regulates activity

0.352

In 293 cells expressing recombinant BRDG1 and various PTKs, Tec and Pyk2, but not Btk, Bmx, Lyn, Syk, or c-Abl, induced marked phosphorylation of BRDG1 on tyrosine residues. BRDG1 was also phosphorylated by Tec directly in vitro. Furthermore, BRDG1 was shown to participate in a positive feedback loop by increasing the activity of Tec. BRDG1 thus appears to function as a docking protein acting downstream of Tec in BCR signaling.

SIGNOR-261818

Q93045

P27361

0

phosphorylation

down-regulates activity

0.352

SCG10, a growth cone-enriched MT-destabilizing protein, has been recently characterized as an in vitro substrate for various serine/threonine kinases including PKA, MAP kinase, and CDK (19). We have found that SCG10 is phosphorylated in vivo in developing rat brain.| The sites for MAP kinase phosphorylation were identified as Ser-62 and Ser-73 of SCG10|By expressing a series of phosphorylation site mutants, we showed that the MT-destabilizing effect of SCG10 could be modulated. While the nonphosphorylatable mutant showed higher activity than the wild-type protein, the activity of the mutant in which phosphorylation on all four sites was mimicked by an aspartate residue was greatly reduced. These data suggest that the nonphosphorylated state of SCG10 represents the most active form of the protein.

SIGNOR-249115

P06748

Q13315

0

phosphorylation

up-regulates activity

0.352

In addition to Serine 125, ATM may also phosphorylate other sites on NPM.

SIGNOR-280182

Q9UHD2

O75688

0

dephosphorylation

down-regulates activity

0.352

PPM1B dephosphorylates TBK1 in vivo and in vitro.|These results demonstrate that PPM1B inhibits TBK1 mediated antiviral signaling by directly dephosphorylating TBK1 at Ser172.

SIGNOR-276985

P47712

O75582

0

phosphorylation

up-regulates activity

0.352

Serine 727 phosphorylation and activation of cytosolic phospholipase A2 by MNK1-related protein kinases.

SIGNOR-249051

Q8TDI7

O75838

0

binding

up-regulates activity

0.352

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-269665

Q9UQL6

Q05655

0

phosphorylation

down-regulates activity

0.352

In this report, we show that VEGF stimulates PKD-dependent phosphorylation of HDAC5 at Ser259/498residues in ECs, which leads to HDAC5 nuclear exclusion and myocyte enhancer factor-2 (MEF2) transcriptional activation.

SIGNOR-260875

O00401

P20929

0

binding

up-regulates

0.352

Igf1-akt signaling, by inhibiting gsk3b, allows the interaction of n-wasp with the unphosphorylated nebulin;the consequent recruitment of n-wasp to the z-disk promotes actin nucleation and elongation of actin filaments.

SIGNOR-175671

Q9HCE7

P31749

0

phosphorylation

up-regulates activity

0.352

Furthermore, phosphorylation of Smurf1 by Akt1 was carried out specifically on the T145 residue, as mutation of this site abolished recognition of Smurf1 by the Akt1 phosphorylation motif antibody (Figure 5D).|We also identified that Smurf1 itself is targeted for phosphorylation by Akt1 and Akt2, regulating its stability.

SIGNOR-279778

P41180

P17252

0

phosphorylation

down-regulates

0.351

Casr(t888) is a protein kinase c (pkc) phosphorylation site in the receptor's intracellular domain that has previously been identified as a critical negative regulator of casr downstream signaling in vitro, thus, casr(t888) represents a functionally important, inhibitory phosphorylation site that contributes to the control of pth secretion.

SIGNOR-170334

Q05586

P05129

0

phosphorylation

up-regulates activity

0.351

Serines 890 and 896 of the NMDA receptor subunit NR1 are differentially phosphorylated by protein kinase C isoforms. The results show that PKC alpha phosphorylates preferentially S896 and PKC gamma preferentially S890.

SIGNOR-263176

Q13586

P28482

0

phosphorylation

up-regulates

0.351

The netrin-2-mediated nfatc3 activation was coincident with robust interactions between cdo and stim1 in myoblasts and the erk-mediated stim1 phosphorylation at serine 575

SIGNOR-192788

Q96P20

Q9UKC9

0

binding

down-regulates quantity by destabilization

0.351

LPS exposure reduces the ubiquitin-mediated proteasomal processing of NALP3 by inducing levels of an E3 ligase component, FBXO3, which targets FBXL2. The latter is an endogenous mediator of NALP3 degradation. FBXL2 recognizes Trp-73 within NALP3 for interaction and targets Lys-689 within NALP3 for ubiquitin ligation and degradation.

SIGNOR-272432

P10586

Q96NI6

0

binding

up-regulates activity

0.351

SALM5 trans-synaptically interacts with LAR-RPTPs in a splicing-dependent manner to regulate synapse development. we identified LAR-RPTPs as novel ligands of SALM5 that mediates SALM5-dependent presynaptic differentiation in a splicing-dependent manner. Our data indicate that SALM5 interacts with all three known LAR-RPTPs—LAR, PTPδ, and PTPσ (Fig. 1).

SIGNOR-264087

Q8IZL8

P11802

0

phosphorylation

up-regulates

0.351

Using site-directed mutagenesis and in vitro kinase assays, we identified ser(477) and ser(991) of pelp1 as cdk phosphorylation sites. we identified pelp1 as a novel substrate of cdks and found that cdk phosphorylation is important for the proper function of pelp1 in modulating hormone-driven cell cycle progression and also for optimal e2f transactivation function.

SIGNOR-167770

P04637

P51948

0

ubiquitination

down-regulates quantity by destabilization

0.351

Collectively, these results indicate that MNAT1 increases p53 ubiquitination, thus promoting its proteasomal degradation.|These suggest that MNAT1 decreases p53 expression by the proteasome.

SIGNOR-278831

P27987

P17612

0

phosphorylation

down-regulates activity

0.351

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

SIGNOR-249995

P23396

P27361

0

phosphorylation

up-regulates

0.351

Erk phosphorylates threonine 42 residue of ribosomal protein s3.

SIGNOR-137175

P55210

Q13177

0

phosphorylation

down-regulates

0.351

Pak2 can bind with caspase-7 and phosphorylate caspase-7 at the ser-30, thr-173, and ser-239 sites. Functionally, the phosphorylation of caspase-7 decreases its activity, thereby inhibiting cellular apoptosis.

SIGNOR-173655

Q9H2G9

O95271

0

ADP-ribosylation

down-regulates quantity by destabilization

0.351

Here, we identify RNF146, a RING-domain E3 ubiquitin ligase, as a positive regulator of Wnt signalling. RNF146 promotes Wnt signalling by mediating tankyrase-dependent degradation of axin. Mechanistically, RNF146 directly interacts with poly(ADP-ribose) through its WWE domain, and promotes degradation of PARsylated proteins. Using proteomics approaches, we have identified BLZF1 and CASC3 as further substrates targeted by tankyrase and RNF146 for degradation.

SIGNOR-263385

O95831

P04637

0

transcriptional regulation

up-regulates quantity by expression

0.351

P53 regulates basal expression of AIF and SCO2 and facilitates oxidative phosphorylation. The expression of GLUT1, GLUT4, and HK2 is negatively regulated by p53, whereas TIGAR expression is induced by p53. The net result of p53-mediated regulation of these glycolytic enzymes is the suppression of glycolysis. In addition, p53 directly binds and inhibits G6PD activity and downregulates the pentose phosphate pathway.

SIGNOR-267462

Q01094

Q16531

0

binding

up-regulates

0.351

We show that ddb, a putative dna repair protein, associates with the activation domain of e2f1 / expression of ddb specifically stimulated e2f1-activated transcription

SIGNOR-54096

Q08050

P45974

0

deubiquitination

up-regulates quantity by stabilization

0.351

Wnt signaling activation inhibits FoxM1 phosphorylation by GSK3-Axin complex and leads to interaction between FoxM1 and deubiquitinating enzyme USP5, thereby deubiquitination and stabilization of FoxM1.

SIGNOR-277210

P50539

P23443

0

phosphorylation

down-regulates activity

0.351

Phosphorylation of Mxi1 by S6K1 at S160 site promotes its binding to beta-Trcp and ubiquitin mediated degradation.|The above findings demonstrate that S6K1 and beta-Trcp negatively regulates the stability of Mxi1 through ubiquitin proteasome pathway.

SIGNOR-278231

P37840

P53350

0

phosphorylation

down-regulates activity

0.351

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

SIGNOR-189045

P12931

Q8N2C7

0

binding

up-regulates activity

0.351

UNC80 is a protein that is associated with the NALCN Na(+) leak cation channel, and is required for the activation of this channel by the neuropeptide substance P through GPCRs in a G-protein-independent fashion. Here, we show that UNC80 binds Src kinases and recruits Src into the channel complex.

SIGNOR-265179

P04637

Q9HCM9

0

ubiquitination

down-regulates quantity by destabilization

0.351

Furthermore, we show here that the Trim39 can directly bind and ubiquitylate p53 in vitro and in vivo, leading to p53 degradation.

SIGNOR-272020

Q02548

P28482

0

phosphorylation

down-regulates activity

0.351

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-269087

O95140

P45984

0

phosphorylation

down-regulates

0.351

Jnk phosphorylation of mitofusin 2 in response to cellular stress leads to recruitment of the ubiquitin ligase (e3) huwe1/mule/arf-bp1/hecth9/e3histone/lasu1 to mitofusin 2, with the bh3 domain of huwe1 implicated in this interaction. This results in ubiquitin-mediated proteasomal degradation of mitofusin 2these data establish that mfn2 is phosphorylated on ser27 in response to a variety of cellular stresses and implicate jnk in this process

SIGNOR-198054

P01236

P31270

0

transcriptional regulation

up-regulates quantity by expression

0.351

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

SIGNOR-261630

Q99856

P78347

0

binding

up-regulates activity

0.35

In this work, we show that TFII-I directly interacts with human Bright through amino acids in Bright's protein interaction domain and that specific tyrosine residues of TFII-I are essential for Bright-induced activity of an immunoglobulin reporter gene. Moreover, inhibition of TFII-I function in a B-cell line resulted in decreased heavy-chain transcript levels.

SIGNOR-268533

P15311

Q9H270

0

binding

up-regulates activity

0.35

The interaction between the full-length Vps11 and ezrin was confirmed by immunoprecipitation and GST-pull down. ERM proteins and the HOPS complex are required for the transition from early to late endosomes

SIGNOR-261311

P23528

Q13418

0

phosphorylation

down-regulates

0.35

Actin (de)polymerization is regulated by cofilin, the ser(3) phosphorylation (ps(3)cofilin) of which inhibits its actin-severing activity. To determine how ilk regulates ps(3)cofilin, we examined the effects of ilk on ps(3)cofilin using normal rie1 cells.

SIGNOR-160756

P19086

P47736

0

binding

down-regulates activity

0.35

Biochemical analysis using purified recombinant proteins revealed that the physical interaction between Gaz and Rap1GAP blocks the ability of RGSs (regulators of G protein signaling) to stimulate GTP hydrolysis of the a subunit, and also attenuates the ability of activated Gaz to inhibit adenylyl cyclase.

SIGNOR-278053

Q06187

P50148

0

binding

up-regulates activity

0.35

AlF− 4-activated Gaq-GDP increased Btk activity as expected, whereas AlF− 4 alone had no stimulatory effect (Table 1), so we conclude that Gaq directly stimulates Btk kinase activity

SIGNOR-278083

P20042

P68400

0

phosphorylation

up-regulates

0.35

The n-terminal domain of the human eif2beta subunit and the ck2 phosphorylation sites are required for its function. These results suggest that ser2 and ser67 contribute to the important role of the n-terminal region of eif2beta for its function in mammals.

SIGNOR-140994

P10914

Q14164

0

phosphorylation

down-regulates activity

0.35

We demonstrated that IKK-ε phosphorylated the transcription factor IFN regulatory factor 1 (IRF-1) at amino acid (aa) 215/219/221 in primary CD4(+) T cells and blocked its transcriptional activity.

SIGNOR-276480

Q99958

Q00535

0

phosphorylation

up-regulates activity

0.35

Cdk5 phosphorylates Foxc2 and activates Foxc2 dependent transcription.

SIGNOR-279156

Q14344

Q9H1C0

0

binding

up-regulates activity

0.35

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-257284

P08235

P27361

0

phosphorylation

down-regulates quantity by destabilization

0.35

Taken together, these data suggest that ERK1/2 directly phosphorylates the MR on several serine residues present in its NTD, that the upward shift of MR is mainly due to receptor phosphorylation, and finally that these sites represent the major aldosterone-inducible targets for MR phosphorylation.MR phosphorylation limits the transcriptional activity.Taken together, these results provide evidence that MR phosphorylation plays a role in aldosterone-mediated ubiquitylation and degradation.

SIGNOR-276102

P11511

P12931

0

phosphorylation

up-regulates

0.35

Phosphorylation of the 361-tyrosine residue is crucial in the up-regulation of aromatase activity. c-src protein directly phosphorylates aromatase on tyrosine 361.

SIGNOR-186284

P01106

Q8TEL6

0

binding

down-regulates quantity by destabilization

0.35

We characterize a new Myc-interacting factor, TRPC4AP (transient receptor potential cation channel, subfamily C, member 4-associated protein)/TRUSS (tumor necrosis factor receptor-associated ubiquitous scaffolding and signaling protein), which is the receptor for a DDB1 (damage-specific DNA-binding protein 1)-CUL4 (Cullin 4) E3 ligase complex for selective Myc degradation through the proteasome. TRPC4AP/TRUSS binds specifically to the Myc C terminus and promotes its ubiquitination and destruction through the recognition of evolutionarily conserved domains in the Myc N terminus.

SIGNOR-271963

P11940

Q9UHC7

0

ubiquitination

up-regulates activity

0.35

We show that MKRN1 directly binds to the cytoplasmic poly(A)-binding protein (PABPC1) and associates with polysomes. MKRN1 is positioned upstream of poly(A) tails in mRNAs in a PABPC1-dependent manner. Ubiquitin remnant profiling and in vitro ubiquitylation assays uncover PABPC1 and ribosomal protein RPS10 as direct ubiquitylation substrates of MKRN1.Our data show that MKRN1 associates with polysomes and ubiquitylates RPS10, indicating a role in translational control. We hypothesize that ribosomes encountering the MKRN1-PABPC1 complex are stalled, possibly via ubiquitylation of RPS10 on K107 and other MKRN1 substrates.

SIGNOR-272215

Q13635

Q9Y625

0

binding

up-regulates activity

0.35

Based on results from in vitro experiments, we had previously proposed that GPC6 stimulates Hh signaling by interacting with Hh and Patched1 (Ptc1), and facilitating/stabilizing their interaction.

SIGNOR-264031

Q96PD2

P06241

0

phosphorylation

up-regulates activity

0.35

Mutagenesis analysis of ESDN's seven intracellular tyrosines in YxxP motifs found several contribute to the binding of ESDN to the SH2 domains of both CrkCT10 regulator of kinase Crk-Like (CrkL) and a representative SFK Fyn. Quantitative mass spectrometry showed that at least three of these (Y565, Y621 and Y750), as well as non-YxxP Y715, are reversibly phosphorylated. SFK activity was shown to be sufficient, but not required for the interaction between ESDN and the CrkL-SH2 domain. Finally, antibody-mediated ESDN clustering induces ESDN tyrosine phosphorylation and CrkL-SH2 binding.

SIGNOR-273946

P56524

P67775

0

dephosphorylation

up-regulates

0.35

Different signal-regulated serine/threonine kinases phosphorylate class ii histone deacetylases (hdacs) to promote nuclear export, cytosolic accumulation, and activation of gene transcriptionhere we show that hdac4 forms a complex with the pp2a holoenzyme c alpha, a alpha, b/pr55 alpha. In vitro and in vivo binding studies demonstrate that the n-terminus of hdac4 interacts with the catalytic subunit of pp2a. Hdac4 is dephosphorylated by pp2a

SIGNOR-159492

P56704

O75487

0

binding

up-regulates

0.35

Gpc4 bound to wnt3a and wnt5a which activate the beta-catenin-dependent and -independent pathways, respectively, and colocalized with wnts on the cell surface. Expression of gpc4 enhanced the wnt3a-dependent beta-catenin pathway and the wnt5a-dependent beta-catenin-independent pathway, and knockdown of gpc4 suppressed both pathways

SIGNOR-195749

P35659

P68400

0

phosphorylation

up-regulates

0.35

Dek is phosphorylated by the protein kinase ck2 in vitro and in vivo on ser32

SIGNOR-125912

P50549

Q15418

0

phosphorylation

up-regulates activity

0.35

Here we describe that the 90-kDa ribosomal S6 kinase 1 (RSK1), a protein kinase downstream of the extracellular signal-regulated kinase (ERK) subclass of MAPKs, binds to ER81, phosphorylates it, and enhances ER81-dependent transcription. Two in vivo RSK1 phosphorylation sites within ER81, Ser(191) and Ser(216), were identified, whose mutation to alanine reduces ER81 activity upon ERK-MAPK stimulation.

SIGNOR-249163

Q13224

P51608

0

transcriptional regulation

down-regulates quantity by repression

0.35

The interaction of MeCP2 with the 2BI3 and 2BI5 sites was strikingly reduced in neurons maintained in the presence of TTX (Fig. 2C). This result is consistent with the classical view of MeCP2 as a general transcriptional repressor, in that the reduced association leads to increased expression of NR2B.

SIGNOR-264685

O94925

P05412

0

transcriptional regulation

up-regulates quantity by expression

0.35

The transcription factor c-Jun can directly bind to the GLS gene promoter and enhance expression

SIGNOR-268035

P63092

Q14832

0

binding

up-regulates activity

0.35

MGluRs are members of the G-protein-coupled receptor (GPCR) superfamily, the most abundant receptor gene family in the human genome. GPCRs are membrane-bound proteins that are activated by extracellular ligands such as light, peptides, and neurotransmitters, and transduce intracellular signals via interactions with G proteins. The resulting change in conformation of the GPCR induced by ligand binding activates the G protein, which is composed of a heterotrimeric complex of α, β, and γ subunits.

SIGNOR-264083

Q9NYJ7

Q86YT6

0

ubiquitination

up-regulates activity

0.35

Mib physically interacts with Delta and promotes its ubiquitination and internalization [66], which have been shown to up-regulate Notch activity.

SIGNOR-209672

Q9UBN4

Q96J02

0

ubiquitination

down-regulates activity

0.35

Ubiquitination of TRPV4 is dramatically increased by the HECT (homologous to E6-AP carboxyl terminus)-family ubiquitin ligase AIP4 without inducing degradation of this channel. Instead, AIP4 promotes the endocytosis of TRPV4 and decreases its amount at the plasma membrane.

SIGNOR-272624

P61586

Q13829

0

binding

down-regulates quantity

0.35

BACURDs form ubiquitin ligase complexes, which selectively ubiquitinate RhoA, with Cul3. Our studies reveal a previously unknown mechanism for controlling RhoA degradation and regulating RhoA function in various biological contexts, which involves a Cul3/BACURD ubiquitin ligase complex.

SIGNOR-264235

P17752

P17612

0

phosphorylation

up-regulates activity

0.35

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

SIGNOR-250062

Q8TEW0

O14965

0

phosphorylation

up-regulates

0.35

Aurora a interacts directly with the atypical protein kinase c binding domain of par3 and phosphorylates it at serine 962. The phosphorylation of par3 at serine 962 contributes to its function in the establishment of neuronal polarity.

SIGNOR-188398

Q92886

Q13164

0

phosphorylation

up-regulates activity

0.35

Activation of ERK5 potentiates while inhibition of ERK5 attenuates Neurog1 stimulated neurogenesis.|ERK5 directly phosphorylated Neurog1 in vitro and modulated the transcriptional and pro-neural activity of Neurog1 in cortical progenitors.

SIGNOR-278364

Q8N137

P51955

0

phosphorylation

down-regulates activity

0.35

The opposite outcomes in NEK2- and centrobin-depleted cells suggest that NEK2 antagonizes biological functions of centrobin.|These results suggest that NEK2 phosphorylates specific sites of centrobin, which are distinct from the PLK1 phosphorylation sites.

SIGNOR-279545

O60885

Q96QE3

0

binding

up-regulates

0.35

ATAD5 Interacts with BRD4 through a Conserved BET Protein-Binding Domain. BRD4-ATAD5 binds to acetyl-histones in nascent chromatin. BRD4 release from chromatin correlates with PCNA unloading. Disruption of the interaction between BRD4 and acetyl-histones or between BRD4 and ATAD5 reduces the PCNA amount on chromatin.

SIGNOR-266412

Q06830

P06493

0

phosphorylation

down-regulates

0.35

Peroxiredoxin (prx) i is a member of the peroxiredoxin family of peroxidases and contains a consensus site (thr(90)-pro-lys-lys) for phosphorylation by cyclin-dependent kinases (cdks). This protein has now been shown to be phosphorylated specifically on thr(90) by several cdks, including cdc2, in vitro. Phosphorylation of prx i on thr(90) reduced the peroxidase activity of this protein by 80%.

SIGNOR-87097

P02461

P03956

0

cleavage

down-regulates quantity by destabilization

0.35

In vitro, MMP1 initiates degradation of native fibrillar collagens, crucial components of vertebrate extracellular matrix (ECM), by cleaving the peptide bond between Gly775–Ile776 or Gly775–Lys776 in native type I, II or III collagen molecules3,4.

SIGNOR-272339

Q9HBA0

P06241

0

phosphorylation

up-regulates activity

0.35

ROS could be detected by Fyn, which is required to activate TRPV4 in a redox-sensitive manner.|The Ca 2+ response to H 2 O 2 required the basal phosphorylation of TRPV4 by the Src kinase Fyn, which may serve as the redox sensor responsible for TRPV4 activation (Figure 2 ) [220] , and was able to increase barrier permeability [219] .

SIGNOR-279991

P11387

P06493

0

phosphorylation

up-regulates activity

0.349

In vitro kinase assays demonstrated that Ser(10) can be phosphorylated by casein kinase II, Ser(21) can be phosphorylated by protein kinase Calpha, and Ser(112) and Ser(394) can be phosphorylated by Cdk1.Collectively these results indicate that topo I is phosphorylated during mitosis at multiple sites, one of which enhances DNA relaxation activity in vitro and interaction with DNA in cells.

SIGNOR-276157

P10415

P17252

0

phosphorylation

up-regulates

0.349

Purified pkca can efficiently and directly phosphorylate bcl2 at serine 70

SIGNOR-60120

P32243

P48436

0

binding

up-regulates activity

0.349

BEST1 promoter activity was increased by SOX9 overexpression and decreased by siRNA-mediated SOX9 knockdown. SOX9 physically interacted with MITF and OTX2 and orchestrated synergistic activation of the BEST1 promoter with the paired SOX site playing essential roles.

SIGNOR-255184

Q14103

P17612

0

phosphorylation

up-regulates

0.349

Protein kinase a enhances, whereas glycogen synthase kinase-3 beta inhibits, the activity of the exon 2-encoded transactivator domain of heterogeneous nuclear ribonucleoprotein d in a hierarchical fashion.

SIGNOR-116144

Q96KS0

Q969H0

0

ubiquitination

down-regulates quantity by destabilization

0.349

Mechanistically, we further show that FBW7, an E3 ligase complex component that is frequently downregulated in TNBC, negatively regulates EglN2 protein stability.

SIGNOR-261997

O15553

Q16513

0

phosphorylation

down-regulates activity

0.349

PKNs bind to human pyrin and phosphorylate S208 and S242. Pyrin forms an inflammasome when mutant or in response to bacterial modification of the GTPase RhoA. We found that RhoA activated the serine-threonine kinases PKN1 and PKN2 that bind and phosphorylate pyrin. Phosphorylated pyrin bound to 14-3-3 proteins, regulatory proteins that in turn blocked the pyrin inflammasome.

SIGNOR-275464

Q7KZI7

P49841

0

phosphorylation

down-regulates activity

0.349

MARK family kinases can be activated by phosphorylation of a conserved threonine (Thr-208 in MARK2), and inactivated by phosphorylation of a serine (Ser-212), both in the activation loop of the catalytic domain. Activation is achieved by the kinases MARKK/TAO1 or LKB1, although the inactivating kinase was unknown. We show here that GSK3beta serves the role of the inhibitory kinase.

SIGNOR-276163

Q00613

Q04759

0

phosphorylation

up-regulates

0.349

At the same time, ea causes pkc?-Mediated phosphorylation and activation of the transcription factor heat shock factor 1, an inducer of glucose dependence.

SIGNOR-200576

O14737

O14829

0

dephosphorylation

down-regulates quantity by destabilization

0.349

Here, we report that the serine/threonine phosphatase PPEF-1 interacts with and dephosphorylates PDCD5 at Ser 119, which leads to PDCD5 destabilization.|These results demonstrate that PPEF-1 reduces PDCD5 stability via PDCD5 dephosphorylation.

SIGNOR-277008

P16144

O14713

0

binding

down-regulates activity

0.349

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-257658

Q01726

Q8TCY5

0

binding

down-regulates activity

0.349

We report that MRAP and MRAP2 can interact with all 5 MCRs. This interaction results in MC2R surface expression and signaling. In contrast, MRAP and MRAP2 can reduce MC1R, MC3R, MC4R, and MC5R responsiveness to [Nle4,D-Phe7]alpha-melanocyte-stimulating hormone (NDP-MSH). MRAP and MRAP2 can reduce the surface expression of MC4R and also the signaling of this receptor. we observed a significant decrease in the cell-surface expression of MC4R and MC5R in the presence of MRAP and MRAP2. It is interesting that MRAP and MRAP2 have opposite effects in the modulation of different MCR family members.

SIGNOR-252364

P46695

Q00987

0

ubiquitination

down-regulates quantity by destabilization

0.349

FHL2 stimulates MDM2 mediated ubiquitination of IER3 by forming a ternary complex.|Scaffold protein FHL2 facilitates MDM2 mediated degradation of IER3 to regulate proliferation of cervical cancer cells.

SIGNOR-278824

Q13444

P06239

0

phosphorylation

up-regulates

0.349

Hck, and to a lesser extent lck, phosphorylated the adam15. Deletion and point mutation analysis of the adam15 cytoplasmic domain confirmed the importance of the proline-rich motifs for grb2 and lck binding and indicated the regulatory nature of tyr(715) and tyr(735). These data demonstrate selective, phosphorylation-dependent interactions of adam15 with src family ptks and grb2, which highlight the potential for integration of adam functions and cellular signaling.

SIGNOR-112931

P63096

P28223

0

binding

up-regulates activity

0.349

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-256742

P61289

O96017

0

phosphorylation

up-regulates activity

0.349

REGγ interacts with DBC1 and is phosphorylated by Chk2.

SIGNOR-273611

O60674

Q5VWQ8

0

binding

down-regulates activity

0.349

In vascular smooth muscle cells (VSMCs) treated with IFN-γ, DAB2IP directly binds to JAK2 and inhibits its kinase activity, limiting JAK-dependent STAT1/3 and PI3K–AKT phosphorylation and activation

SIGNOR-254760

O00429

Q9UM11

0

ubiquitination

down-regulates quantity

0.349

Here we demonstrate that changes in mitochondrial dynamics as cells exit mitosis are driven in part through ubiquitylation of Drp1 catalyzed by the APC/Ccdh1 (anaphase-promoting complex/cyclosome and its coactivator (Cdh1) E3 ubiquiting ligase complex

SIGNOR-274127

P09471

P08172

0

binding

up-regulates activity

0.349

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-256964

P53350

P49137

0

phosphorylation

up-regulates

0.349

Here, we have identified mk2 as a major plk1 kinase toward ser326, whose phosphorylation is critical to recruit ?-Tubulin to centrosomes and subsequent establishment of functional bipolar spindles. To our knowledge, this is the first direct evidence to demonstrate that the essential function of plk1 in centrosome maturation and bipolar spindle formation is controlled by its upstream kinase.

SIGNOR-179968

P78352

Q05086

0

ubiquitination

down-regulates quantity by destabilization

0.349

E6-induced degradation of DLG4 depends on E6AP in vivo. Our findings as a whole indicate that E6AP is involved in E6-mediated ubiquitination and degradation of DLG4 both in vivo and in vitro.

SIGNOR-271397

Q99607

Q13315

0

phosphorylation

down-regulates activity

0.349

Elf4 is phosphorylated by Atm after gamma irradiation, leading to its degradation.|Thus, Atm promotes Elf4 protein degradation after gamma irradiation via phosphorylation at these sites.

SIGNOR-278466

P01106

Q8N1E6

0

ubiquitination

down-regulates quantity by destabilization

0.349

In this study, we demonstrate that the deubiquitinase USP13 stabilizes c-Myc by antagonizing FBXL14-mediated ubiquitination to maintain GSC self-renewal and tumorigenic potential. USP13 was preferentially expressed in GSCs, and its depletion potently inhibited GSC proliferation and tumor growth by promoting c-Myc ubiquitination and degradation.

SIGNOR-274125

P01112

Q7Z5G4

0

palmitoylation

up-regulates activity

0.349

Covalent lipid modifications mediate the membrane attachment and biological activity of Ras proteins. All Ras isoforms are farnesylated and carboxyl-methylated at the terminal cysteine; H-Ras and N-Ras are further modified by palmitoylation. Here we report that H- and N-Ras are palmitoylated by a human protein palmitoyltransferase encoded by the ZDHHC9 and GCP16 genes. DHHC9 is an integral membrane protein that contains a DHHC cysteine-rich domain. GCP16 encodes a Golgi-localized membrane protein.

SIGNOR-261351

P17600

Q13153

0

phosphorylation

up-regulates activity

0.349

Synapsin I is phosphorylated at Ser603 by p21-activated kinases. the Ser603 residue must be one of the pivotal sites for the release

SIGNOR-250235

Q16665

Q9H4B4

0

phosphorylation

down-regulates

0.348

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

SIGNOR-178743

Q00613

P19784

0

phosphorylation

up-regulates

0.348

Transcriptional activity and dna binding of heat shock factor-1 involve phosphorylation on threonine 142 by ck2.As hsf1 is activated by heat shock simultaneously with the nuclear translocation of the protein kinase ck2, we have investigated the role of ck2 in hsf1 activatio

SIGNOR-99606

O95863

P68400

0

phosphorylation

up-regulates quantity by stabilization

0.348

Serines 11 and 92 participate in the control of snail1 stability and positively regulate snail1 repressive function and its interaction with msin3a corepressor. Furthermore, serines 11 and 92 are required for snail1-mediated emt and cell viability, respectively. Pka and ck2 have been characterized as the main kinases responsible for in vitro snail1 phosphorylation at serine 11 and 92, respectively.

SIGNOR-161771

P41594

Q05655

0

phosphorylation

up-regulates activity

0.348

Thus, we showed that it is phosphorylation of Ser-839, not Thr-840, that is absolutely required for the unique Ca2+ oscillations produced by mGluR5 activation. The Thr-840 residue is important only in that it is permissive for the PKC-dependent phosphorylation of Ser-839.

SIGNOR-249287

Q9Y6R1

Q9UEW8

0

phosphorylation

down-regulates activity

0.348

SPAK phosphorylates the transporters to reduce their surface expression and thus their activity and consequently inhibits ductal secretion to stabilize the resting state. PP1 reverses the effect of SPAK. Molecular analysis revealed that the WNK kinases acted as scaffolds to recruit SPAK, which phosphorylated CFTR and NBCe1-B, reducing their cell surface expression.

SIGNOR-263133

Q16625

Q96J02

0

ubiquitination

down-regulates quantity by destabilization

0.348

Two mechanisms regarding junction protein turnover were illustrated in this process, that is, the Itch-induced occludin ubiquitination and proteasome degradation, and the caveolae-dependent endocytosis of junction proteins (JAM-A, N-cadherin, and \u03b2 -catenin), both of which led to the instability of junction apparatus between adjacent SCs and a subsequent damaged BTB.

SIGNOR-278756

O15297

P06493

0

phosphorylation

down-regulates quantity by destabilization

0.348

Phosphorylation of multiple residues in the catalytic domain of PPM1D during mitosis, including Ser40 by Cyclin-dependent kinase 1 (CDK1), leads to ubiquitination of PPM1D and subsequent proteasomal degradation by Adenomatous polyposis coli (APC) and cell-division cycle protein 20 (CDC20)

SIGNOR-275489

P30307

P11309

0

phosphorylation

up-regulates activity

0.348

First, Pim-1 activates the Cdc25C phosphatase directly through phosphorylation, very probably at the N-terminal part of the protein.|We find that phosphorylation by Pim-1 enhances the phosphatase activity of Cdc25C and in transfected cells that are arrested in G2/M by bleomycin, Pim-1 can enhance progression into G1.

SIGNOR-278298

Q9NPF5

Q7Z553

0

binding

up-regulates quantity by stabilization

0.348

The anti-tumorigenic effect of MDGA2 was mediated through direct stabilising of DNA methyltransferase 1 associated protein 1 (DMAP1), which played a tumour suppressive role in gastric cancer. MDGA2 expression and MG132 treatment increased the level of DMAP1, suggesting that the MDGA2–DMAP1 interaction stabilises DMAP1 by inhibiting its ubiquitin-mediated degradation.

SIGNOR-264240

Q99828

P60763

0

binding

up-regulates activity

0.348

We here report that CIB, a protein that binds to the alpha(IIb)beta(3) fibrinogen receptor, interacts exclusively with activated (V12) Rac3 but not Rac1 or Rac2. Binding of V12Rac3 to CIB was mediated by the C-terminal end of Rac3 and by Rac3 membrane localization

SIGNOR-269060

Q07955

O43187

0

phosphorylation

down-regulates activity

0.348

IRAK2 phosphorylates SRSF1 and thereby reduces SRSF1 binding to the target mRNAs.

SIGNOR-278406

P35590

Q02763

0

phosphorylation

up-regulates activity

0.348

Thus, Tie2 was able to induce Tie1 phosphorylation.|When cotransfected, Tie2 formed heteromeric complexes with Tie1, enhanced Tie1 activation, and induced phosphorylation of a kinase-inactive Tie1 in a ligand-dependent manner.

SIGNOR-279769

P42224

P22455

0

phosphorylation

up-regulates activity

0.348

Activation of Stat1 and Stat3 by FGFR derivatives. Lysates of 293T cells transfected as indicated were analysed by Western blotting using Phospho-Stat1 (Y701) antisera (top) or Stat1 antisera (bottom). (b) The same lysates in (a) were re-examined for phosphorylated Stat3 by Western blotting with Phospho-Stat3 (Y705) (top). all three FGFR family members examined here are able to lead to Stat activation. Expression of the 'TDII-like' derivatives of FGFR1, FGFR3, and FGFR4, as well as myrR1-WT, led to phosphorylation of both Stat1 and Stat3.

SIGNOR-251141