GleghornLab/Signor_processed · Datasets at Hugging Face

IdA stringlengths 6 21	IdB stringlengths 6 21	labels float64 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
Q9UH77	Q96J92	1	binding	down-regulates quantity by destabilization	0.585	Here, we found that KLHL3 interacted with Cullin3 and WNK4, induced WNK4 ubiquitination, and reduced the WNK4 protein level. The reduced interaction of KLHL3 and WNK4 by PHAII-causing mutations in either protein reduced the ubiquitination of WNK4, resulting in an increased level of WNK4 protein.	SIGNOR-272105
Q5SGD2	O43318	1	dephosphorylation	down-regulates activity	0.585	Co-immunoprecipitation experiments indicated that PP2Cepsilon associates stably with TAK1 and attenuates the binding of TAK1 to MKK4 or MKK6.\|PP2Cepsilon dephosphorylated TAK1 in vitro.	SIGNOR-277114
P00519	Q00535	1	phosphorylation	up-regulates activity	0.585	Phosphorylation of Cdk5 by c-Abl occurs on tyrosine 15 (Y15), which is stimulatory for p35/Cdk5 kinase activity.	SIGNOR-245288
P15391	P27986	1	binding	up-regulates activity	0.585	CD19 has an extracellular region containing two C2-type Ig-like domains and a cytoplasmic region of ~240 amino acids with 9 conserved tyrosine residues24. Lyn, a Src-family protein tyrosine kinase member, is the dominant kinase that phosphorylates CD19 upon stimulation. Once tyrosyl-phosphorylated, CD19 serves as a membrane-bound adaptor protein for Src homology 2-containing signaling molecules such as Lyn, Vav, and phosphatidylinositol 3-kinase, which further mediate downstream activation cascades.	SIGNOR-242900
P12931	O15530	1	phosphorylation	up-regulates activity	0.585	Using site-directed mutants, we show that, although phosphorylation on tyr-373/376 is important for pdk1 activity, phosphorylation on tyr-9 has no effect on the activity of the kinase. Both of these residues can be phosphorylated by v-src tyrosine kinase in vitro, and co-expression of v-src leads to tyrosine phosphorylation and activation of pdk1.	SIGNOR-109533
P35348	P50148	1	binding	up-regulates activity	0.585	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-257084
P06493	Q8NHV4	1	phosphorylation	up-regulates activity	0.585	Here we report that the function of Nedd1 is regulated by Cdk1 and Plk1. During mitosis, Nedd1 is firstly phosphorylated at T550 by Cdk1, which creates a binding site for the polo-box domain of Plk1. Then, Nedd1 is further phosphorylated by Plk1 at four sites: T382, S397, S637 and S426. The sequential phosphorylation of Nedd1 by Cdk1 and Plk1 promotes its interaction with gamma-tubulin for targeting the gammaTuRC to the centrosome and is important for spindle formation.	SIGNOR-272973
Q99985	O60462	1	binding	up-regulates	0.585	Our experiments establish that small peptides containing the consensus decd sequence of sperm fertilinbeta bind specifically to an alpha6beta1 integrin receptor on the egg membrane. We conclude that fertilinbeta binds directly to the alpha6beta1 integrin on the egg surface and this partnership mediates sperm-egg fusion.	SIGNOR-147564
Q8IYT4	Q9BVA0	1	binding	up-regulates activity	0.585	Katanin, a heterodimeric microtubule-severing ATPase, is found localized at mitotic spindle poles. In this paper we demonstrate that human p60 katanin and the C-terminal domain of human p80 katanin both bind microtubules in vitro. Association of these two proteins results in an increased microtubule affinity and increased microtubule-severing activity in vitro. Association of these subunits in transfected HeLa cells increases microtubule disassembly activity and targeting to spindle poles.	SIGNOR-267180
O60716	P63000	1	binding	up-regulates	0.585	We demonstrate that p120-catenin participates in the stimulation of rac1 activity, binding directly to this protein. In addition we show that vav2 also binds to p120-catenin and is required for rac1 activation and for beta-catenin translocation to the nucleus.Vav2 And rac1 association with p120-catenin was modulated by phosphorylation of this protein, which was stimulated upon serine/threonine phosphorylation by ck1 and inhibited by tyrosine phosphorylation by src or fyn	SIGNOR-198938
P25100	P50148	1	binding	up-regulates activity	0.585	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-257080
Q9Y490	P26010	1	binding	up-regulates activity	0.585	Over the past 10 years, the binding of talin to the cytoplasmic tail of integrin-β subunits has been established to have a key role in integrin activation. Binding of the phosphotyrosinebinding (PTB)-domain-like subdomain of the protein 4.1, ezrin, radixin, moesin (FERM) domain of talin to the conserved WxxxNP(I/L)Y motif of the β-integrin tail permits additional weaker interactions between talin and the membrane-proximal region of the tail that trigger integrin activation, probably through the disruption of inhibitory interactions between α- and β-subunit cytoplasmic tails.	SIGNOR-257633
O43283	O14733	1	phosphorylation	up-regulates	0.584	Lzk directly phosphorylated and activated mkk7.	SIGNOR-112349
Q9Y2E6	Q9UHD2	1	ubiquitination	down-regulates	0.584	Nlrp4 negatively regulates type i interferon signaling by targeting the kinase tbk1 for degradation via the ubiquitin ligase dtx4	SIGNOR-71565
O14965	Q99661	1	phosphorylation	down-regulates activity	0.584	In addition, we found that MCAK localization at spindle poles was regulated through another Aurora A phosphorylation site (S719), which positively enhances bipolar spindle formation.	SIGNOR-279139
Q13418	O14974	1	phosphorylation	down-regulates activity	0.584	MYPT1 was phosphorylated by ILK and phosphorylation sites in the N- and C-terminal fragments of MYPT1 were detected. From sequence analyses, three sites were identified: a primary site at Thr(709), and two other sites at Thr(695) and Thr(495). ILK produced an intermediate level of inhibition	SIGNOR-262884
Q6UXZ4	P43146	1	binding	down-regulates activity	0.584	In the presence of netrin-1, UNC5 co-immuno-precipitates with DCC, suggesting the formation of a ternary complex of netrin-1 with ecto-domains of DCC and UNC5. DCC binding to netrin-1 alone leads to axon attraction. Importantly, DCC has the ability to switch the netrin-1-mediated responses from attraction to repulsion when another receptor UNC5 co-exists. DCC binding to netrin-1 alone leads to axon attraction. Importantly, DCC has the ability to switch the netrin-1-mediated responses from attraction to repulsion when another receptor UNC5 co-exists.	SIGNOR-268167
O14640	P63000	1	binding	up-regulates activity	0.584	B-catenin-independent wnt signaling can activate rho family gtpases through at least two mechanisms: (1) direct activation of rac1 by dvl;and (2) activation of rhoa via dvl-associated activator of morphogenesis-1 (daam1), possibly through the weak-similarity guaninenucleotide exchange factor (wgef)1.	SIGNOR-185274
P15976	P56524	1	relocalization	up-regulates activity	0.584	GATA1 is a new substrate of p21-activated kinase 5 (PAK5), which is phosphorylated on serine 161 and 187 (S161 and S187). GATA1 recruits HDAC3/4 to E-cadherin promoter, which is reduced by GATA1 S161A S187A mutant. These data indicate that phosphorylated GATA1 recruits more HDAC3/4 to promote transcriptional repression of E-cadherin, leading to the EMT of breast cancer cells.	SIGNOR-275665
Q07812	P21796	1	binding	up-regulates activity	0.584	The recombinant pro-apoptotic proteins Bax and Bak accelerate the opening of VDAC	SIGNOR-249613
O43663	Q02224	1	binding	up-regulates activity	0.584	These data indicate that PRC1 binds to KIF4, MKLP1 and CENP-E during late mitosis; however, it apparently does not interact simultaneously with more than one of these motor proteins.	SIGNOR-265990
P10721	Q14451	1	binding	up-regulates activity	0.584	We furthermore demonstrate that the adapter protein Grb2 is a specific binding partner for both phosphorylated Tyr-703 and phosphorylated Tyr-936, whereas the adapter protein Grb7 binds selectively to phosphorylated Tyr-936.	SIGNOR-248291
P49137	P11831	1	phosphorylation	up-regulates	0.584	Neverthless, some transcription factors, such as e47, er81, srf and creb are also phosphorylated by mk2	SIGNOR-166640
Q15831	P57059	1	phosphorylation	up-regulates	0.584	Lkb1 is a master kinase that activates 13 kinases of the ampk subfamily, including mark/par-1we recently demonstrated that the lkb1 tumour suppressor kinase, in complex with the pseudokinase strad and the scaffolding protein mo25, phosphorylates and activates amp-activated protein kinase (ampk). A total of 12 human kinases (nuak1, nuak2, brsk1, brsk2, qik, qsk, sik, mark1, mark2, mark3, mark4 and melk) are related to ampk. Here we demonstrate that lkb1 can phosphorylate the t-loop of all the members of this subfamily, apart from melk, increasing their activity >50-fold	SIGNOR-122784
O75925	Q9UPW6	1	sumoylation	down-regulates activity	0.583	We found that SATB2 differs from the closely related thymocyte-specific protein SATB1 by modifications of two lysines with the small ubiquitive related modifier (SUMO), which are augmented specifically by the SUMO E3 ligase PIAS1.	SIGNOR-269112
P43246	P54132	1	binding	up-regulates	0.583	We show that the recombinant hmsh2/6 protein complex stimulated the ability of the bloom's syndrome gene product, blm, to process holliday junctions in vitro	SIGNOR-123699
Q3KR16	P61586	1	guanine nucleotide exchange factor	up-regulates activity	0.583	We therefore developed a screening-compatible live-cell imaging assay, using FRET-based biosensors for the prototype GTPases RHOA, RAC1 and CDC4215,19,20 (Extended Data Fig. 2 and Supplementary Note 1)\|We found catalytic activities for 45/75 RhoGEFs and 48/63 RhoGAPs\| Our data thus not only reveal extensive promiscuity among regulators, but also that the inactivating RhoGAPs are less selective than the activating RhoGEFs (p-value=0.02)(Supplementary Table 2).	SIGNOR-260567
P53350	O15392	1	phosphorylation	up-regulates	0.583	Thus, we conclude that plk1-mediated phosphorylation of sur at ser20 is critical for accurate chromosome segregation\|SUR (survivin)	SIGNOR-170460
P04637	P11413	1	binding	down-regulates activity	0.583	The p53 protein binds to glucose-6-phosphate dehydrogenase (G6PD), the first and rate-limiting enzyme of the PPP, and prevents the formation of the active dimer.	SIGNOR-267468
Q13145	Q13467	1	binding	up-regulates	0.583	These data together suggest that bambi may form a ternary coreceptor complex with fzd5 and lrp6	SIGNOR-23040
Q96JJ3	P63000	1	guanine nucleotide exchange factor	up-regulates activity	0.583	We found in this study that AUTS2 is involved in Rac1 activation via P-Rex1 and the Elmo2/Dock180 complex, but not STEF or Tiam1, for the lamellipodia formation in N1E-115 cells. However, the enhancement of neurite elongation in primary neurons by AUTS2 expression is specifically mediated by the Elmo2/Dock180 complex. These results suggested that several Rac-GEFs differentially or cooperatively participate in Rac1 activation to promote neuronal migration and neurite outgrowth.	SIGNOR-266821
Q9UHD9	Q13148	1	binding	down-regulates quantity by destabilization	0.583	Here, we describe a high affinity interaction between UBQLN2 and TDP-43 and demonstrate that overexpression of both UBQLN2 and TDP-43 reduces levels of both exogenous and endogenous TDP-43 in human H4 cells.\|Consequently, these data suggest that UBQLN2 enhances the clearance of TDP-43	SIGNOR-262112
P08311	P25116	1	cleavage	down-regulates activity	0.583	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.\|Protease-activated receptors (PARs) mediate cell activation after proteolytic cleavage of their extracellular amino terminus.\|Plasmin, calpain and leukocyte elastase, cathepsin G, and proteinase 3 cleaved at multiple sites and would be expected to disable PAR1 by cleaving COOH-terminal to the activation site.	SIGNOR-263564
P28482	P06239	1	phosphorylation	up-regulates activity	0.583	Phosphorylation at Ser-59 (or alternatively, its mutation to Glu) reverses the inhibition and allows interaction of the p56lck SH2 domain with p62.\|phosphotyrosine-independent binding of p62 to the p56lck SH2 domain appears to provide an alternative pathway for p56lck signaling that is regulated by Ser-59 phosphorylation.	SIGNOR-249412
Q6ZMZ0	Q9NWZ5	1	ubiquitination	down-regulates quantity by destabilization	0.583	We demonstrated that both UbcH7 and UbcH8 bind to full-length NKLAM. We demonstrated decreased protein expression and enhanced ubiquitination of URKL-1 in the presence of NKLAM. These data indicate that NKLAM is a RING finger protein that binds Ubcs and has as one of its substrates, URKL-1, thus defining this cytolytic protein as an E3 ubiquitin ligase.	SIGNOR-271590
P27348	Q14814	1	binding	up-regulates	0.583	14-3-3tau associates with and activates the mef2d transcription factor during muscle cell differentiation.	SIGNOR-109139
Q13469	Q14814	1	binding	up-regulates	0.583	Upon dephosphorylation by calcineurin, nfatc2, also referred to as nfatp/nfat1, translocates to the nucleus where it directly associates with mef2a and -d. Nfatc2 stimulates mef2-dependent transcription by facilitating recruitment of the p300 coactivator to mef2-response elements.	SIGNOR-117589
P41134	Q99081	1	binding	down-regulates activity	0.583	All three Ids bound with high affinity to E proteins .Each Id was able to disrupt the ability of E protein-MyoD complexes to transactivate from a muscle creatine kinase reporter construct in vivo.	SIGNOR-241104
P62993	Q92835	1	binding	up-regulates activity	0.583	An adaptor protein Dok-3 mediates the suppressive function of LYN. The Dok-3 phosphorylated by LYN upon BCR stimulation forms a complex with GRB2, which allows it to enter into the signalosome and associate with activation of SHIP protein. This translocation facilitates the efficient inhibition of PLCc2 and SYK from activation, subsequently resulting in the suppression of downstream Ca2+ signaling.	SIGNOR-268449
P12931	P08069	1	phosphorylation	up-regulates activity	0.582	The insulin-like growth factor type I (IGF-I) receptor can become tyrosine phosphorylated and enzymatically activated either in response to ligand or because of the activity of the Src tyrosine kinaseWe mapped the sites of IGF-I receptor autophosphorylation to peptides representing three different receptor domains: tyrosines 943 and 950 in the juxtamembrane region; tyrosines 1131, 1135, and 1136 within the kinase domain; and tyrosine 1316 in the carboxyl-terminal domain.	SIGNOR-247193
P25116	P50148	1	binding	up-regulates activity	0.582	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-257219
O14733	P53779	1	phosphorylation	up-regulates	0.582	Two mapkks, sek1 and mkk7, synergistically activate jnk. Sek1 prefers the tyr-185 residue, and mkk7 prefers the thr-183 residue (17, 19).	SIGNOR-137609
O95819	O43318	1	binding	up-regulates	0.582	The existence of an at least trimolecular complex consisting of nik, tak1, and ikk2, although the precise sequence of activation as well as the possible location of the kinases within the signalosome remains to be elucidated.	SIGNOR-77404
Q14669	Q8N726	1	ubiquitination	down-regulates quantity by destabilization	0.582	ULF interacts with ARF both in vitro and in vivo and promotes the lysine-independent ubiquitylation and degradation of ARF.	SIGNOR-266781
O95295	P60880	1	binding	up-regulates activity	0.582	In the present study, we used yeast two-hybrid analysis to identify a new binding partner of torsinA, the SNARE-associated protein snapin. We have reported that snapin shows a robust interaction with wild type and mutant torsinA. we have demonstrated that this portion of torsinA and/or the adjacent linker region has the additional role of recruiting snapin. we found that snapin, which binds SNAP-25 (synaptosome-associated protein of 25,000 Da) and enhances the association of the SNARE complex with synaptotagmin, is an interacting partner for both wild type and mutant torsinA.	SIGNOR-261171
P45983	P10415	1	phosphorylation	down-regulates	0.582	G(2)/m-phase cells proved more susceptible to death signals, and phosphorylation of bcl-2 appeared to be responsible, as a ser70ala substitution restored resistance to apoptosis. We noted that ask1 and jnk1 were normally activated at g(2)/m phase, and jnk was capable of phosphorylating bcl-2..	SIGNOR-72361
P00519	Q9UPY6	1	phosphorylation	up-regulates activity	0.582	WAVE3-Abl interaction promotes the tyrosine phosphorylation of WAVE3 by Abl, and STI-571, a specific inhibitor of Abl kinase activity, abrogates the Abl-mediated phosphorylation of WAVE3.	SIGNOR-259077
Q9Y297	Q15653	1	binding	down-regulates quantity by destabilization	0.582	Interaction with beta-TrCP is also necessary for ubiquitination of IkappaBbeta upon stimulation of cells, and deletion of the F-box in beta-TrCP abolishes its ability to ubiquitinate IkappaBbeta. Therefore, these results indicate that beta-TrCP plays a critical role in the activation of NF-kappaB by assembling the ubiquitin ligase complex for both phosphorylated IkappaBalpha and IkappaBbeta.β-TrCP recognizes IκBα phosphorylated at Ser-32 and Ser-36 through its WD40 domain, whereas the F-box motif recruits additional proteins including Skp1 and Cullin to form the Skp1-cullin-F-box (SCF) ubiquitin ligase complex	SIGNOR-272554
Q15311	P63000	1	gtpase-activating protein	down-regulates activity	0.582	We therefore developed a screening-compatible live-cell imaging assay, using FRET-based biosensors for the prototype GTPases RHOA, RAC1 and CDC4215,19,20 (Extended Data Fig. 2 and Supplementary Note 1)\|We found catalytic activities for 45/75 RhoGEFs and 48/63 RhoGAPs\| Our data thus not only reveal extensive promiscuity among regulators, but also that the inactivating RhoGAPs are less selective than the activating RhoGEFs (p-value=0.02)(Supplementary Table 2).	SIGNOR-260513
Q13216	Q03468	1	ubiquitination	down-regulates quantity by destabilization	0.582	We have previously shown that CSA is a subunit of an E3 ubiquitin ligase complex. Here we demonstrate that CSB is a substrate of this ligase: Following UV irradiation, CSB is degraded at a late stage of the repair process in a proteasome- and CSA-dependent manner.	SIGNOR-271406
Q5VWK5	P29597	1	binding	up-regulates	0.582	Il-23 activates the same jak-stat signaling molecules as il-12: jak2, tyk2, and stat1, -3, -4, and -5, but stat4 activation is substantially weaker and different dna-binding stat complexes form in response to il-23 compared with il-12.	SIGNOR-87841
P19793	Q03181	1	binding	up-regulates	0.582	Although the three ppar subtypes are closely related and bind to similar dna response elements as heterodimers with the 9-cis retinoic acid receptor rxr, each subserves a distinct physiology	SIGNOR-105442
Q12913	P09619	1	dephosphorylation	down-regulates activity	0.582	Primary sequence determinants responsible for site-selective dephosphorylation of the PDGF beta-receptor by the receptor-like protein tyrosine phosphatase DEP-1\|DEP-1 dephosphorylation of original and chimeric phospho-peptides spanning the preferred pY1021	SIGNOR-248704
P04637	P54278	1	transcriptional regulation	up-regulates quantity	0.582	.... numerous potentially novel targets, including the DNA mismatch repair genes MLH1 and PMS2. Both of these genes were determined to be responsive to DNA damage and p53 activation in normal human fibroblasts, and have p53-response elements within their first intron.	SIGNOR-257604
Q13153	Q02750	1	phosphorylation	up-regulates activity	0.582	We find that adhesion to fibronectin induces pak1-dependent phosphorylation of mek1 on s298 and that this phosphorylation is necessary for efficient activation of mek1 and subsequent mapk activation.	SIGNOR-236002
P30874	P63096	1	binding	up-regulates activity	0.582	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-256684
P53779	P05067	1	phosphorylation	up-regulates	0.582	Phosphorylation of amyloid precursor protein at threonine 668 is essential for its copper-responsive trafficking in sh-sy5y neuroblastoma cells. is regulated by jnk3 via phosphorylation of app at thr668	SIGNOR-204671
P31749	P04406	1	phosphorylation	down-regulates activity	0.582	GAPDH is phosphorylated by protein kinase B (AKT) on T237, which prevents GAPDH nuclear translocation and suppresses GAPDH mediated apoptosis.\|GAPDH is phosphorylated by protein kinase B (AKT) on T237, which prevents GAPDH nuclear translocation and suppresses GAPDH-mediated apoptosis ( ).	SIGNOR-280174
O75385	Q7Z3C6	1	phosphorylation	up-regulates activity	0.582	Src phosphorylates mATG9 at Tyr8 to maintain its endocytic and constitutive trafficking in unstressed conditions. In response to starvation, phosphorylation of mATG9 at Tyr8 by Src and at Ser14 by ULK1 functionally cooperate to promote interactions between mATG9 and the AP1/2 complex, leading to redistribution of mATG9 from the plasma membrane and juxta-nuclear region to the peripheral pool for autophagy initiation.	SIGNOR-266369
Q9Y6F9	O75197	1	binding	up-regulates	0.581	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-131894
Q53QZ3	P63000	1	gtpase-activating protein	down-regulates activity	0.581	We therefore developed a screening-compatible live-cell imaging assay, using FRET-based biosensors for the prototype GTPases RHOA, RAC1 and CDC4215,19,20 (Extended Data Fig. 2 and Supplementary Note 1)\|We found catalytic activities for 45/75 RhoGEFs and 48/63 RhoGAPs\| Our data thus not only reveal extensive promiscuity among regulators, but also that the inactivating RhoGAPs are less selective than the activating RhoGEFs (p-value=0.02)(Supplementary Table 2).	SIGNOR-260470
P0DP24	Q08209	1	binding	up-regulates	0.581	Calcium-bound calmodulin associates with calcineurin (cn), releasing the phosphatase from the repressive effects on an autoinhibitory domain.	SIGNOR-266327
P17612	P16220	1	phosphorylation	up-regulates activity	0.581	Using a combination of in vitro explant assays, mutant analysis and gene delivery into mouse embryos cultured ex vivo, we demonstrate that adenylyl cyclase signalling via PKA and its target transcription factor CREB are required for WNT-directed myogenic gene expression.	SIGNOR-131307
P50613	P06493	1	phosphorylation	up-regulates	0.581	The mo15 gene encodes the catalytic subunit of a protein kinase that activates cdc2 and other cyclin-dependent kinases (cdks) through phosphorylation of thr161 and its homologues	SIGNOR-38307
P23467	P33151	1	dephosphorylation	up-regulates activity	0.581	Because we had shown previously that VE-PTP supports VE-cadherin function when exogenously expressed in transfected cells, we expected it to be expressed at endothelial cell contacts.\|Indeed, tyrosine phosphorylation of VE-cadherin is reduced by VE-PTP in COS-7 and CHO cells.	SIGNOR-277131
P68400	P25963	1	phosphorylation	down-regulates	0.581	Casein kinase ii phosphorylates i kappa b alpha at s-283, s-289, s-293, and t-291 and is required for its degradation.	SIGNOR-40502
O75509	Q15628	1	binding	up-regulates	0.581	Dr6 interacts with tradd	SIGNOR-100184
Q96PM5	Q9Y253	1	monoubiquitination	down-regulates activity	0.581	Pirh2 E3 ubiquitin ligase monoubiquitinates DNA polymerase eta to suppress translesion DNA synthesis. Specifically, we show that Pirh2, a target of the p53 tumor suppressor, monoubiquitinates PolH at one of multiple lysine residues.we show that monoubiquitination of PolH alters the ability of PolH to translocate to replication foci for translesion DNA synthesis of UV-induced DNA lesions.These results suggest that Pirh2 monoubiquitinates PolH at one of the four lysine residues (K682, K686, K694, and K709).	SIGNOR-272733
P67775	Q08999	1	dephosphorylation	up-regulates	0.581	Pocket protein family consists of the retinoblastoma tumor suppressor protein (prb) and the functionally and structurally related proteins p107 and p130./dephosphorylation of p130 and p107 in cell extracts is inhibited by concentrations of okadaic acid known to inhibit pp2a, but not pp1. Finally, the pp2a catalytic subunit pp2a/c) specifically interacts with both p130 and p107 / the cell cycle repressor activity of pocket proteins is inactivated by cdk mediated phosphorylation.	SIGNOR-129752
Q96SW2	Q9UKT9	1	ubiquitination	down-regulates quantity by destabilization	0.581	IMiD compounds cause selective ubiquitination and degradation of IKZF1 in CD34+ cells by the CRBN E3 ubiquitin ligase.	SIGNOR-272319
Q06187	P19174	1	phosphorylation	up-regulates activity	0.581	Then, BTK and ITK are activated by Src kinases and proceed to phosphorylate the lipase PLCgamma2 / PLCgamma1, which cleaves PIP2 in the plasma membrane and generates the secondary messengers IP3 and DAG.	SIGNOR-279444
P06493	Q9BZB8	1	phosphorylation	up-regulates activity	0.581	Combined, our results suggest that XGef is involved in XRINGO and CDK1 mediated activation of CPEB and that an XGef, XRINGO, ERK2, and CPEB complex forms in ovo to facilitate this process.\|Notably, specific inhibition of XRINGO and CDK1 activity in CPEB phosphorylation-competent extracts completely blocks phosphorylation of CPEB, which suggests that XRINGO and CDK1 directly phosphorylates CPEB.	SIGNOR-280205
Q5S007	O14966	1	phosphorylation	up-regulates activity	0.581	In an attempt to mimic phosphorylation of Rab29 by LRRK2, we mutated the phosphorylation sites to Glu and observed that the Rab29[T71E,S72E] mutant failed to activate LRRK2 (Fig\u00a0 xref B).\|To test whether phosphorylation of Rab29 at Thr71 and Ser72 by LRRK2 was required for activation of LRRK2, we mutated these sites both to Ala.	SIGNOR-279474
Q86T82	P20248	1	deubiquitination	up-regulates quantity by stabilization	0.581	USP37 Binds, Deubiquitinates, and Stabilizes Cyclin A	SIGNOR-265052
O43182	P61586	1	gtpase-activating protein	down-regulates activity	0.581	We therefore developed a screening-compatible live-cell imaging assay, using FRET-based biosensors for the prototype GTPases RHOA, RAC1 and CDC4215,19,20 (Extended Data Fig. 2 and Supplementary Note 1)\|We found catalytic activities for 45/75 RhoGEFs and 48/63 RhoGAPs\| Our data thus not only reveal extensive promiscuity among regulators, but also that the inactivating RhoGAPs are less selective than the activating RhoGEFs (p-value=0.02)(Supplementary Table 2).	SIGNOR-260462
P61457	P35680	1	binding	up-regulates activity	0.581	Overexpression in a human kidney cell line showed that wild-type PCBD1 binds HNF1B to costimulate the FXYD2 promoter, the activity of which is instrumental in Mg(2+) reabsorption in the DCT.	SIGNOR-254910
P51151	Q7Z6M1	1	null	up-regulates activity	0.581	P40 is a very potent transport factor in that the pure, recombinant protein can stimulate, significantly, an in vitro transport assay that measures transport of mannose 6-phosphate receptors from endosomes to the trans-Golgi network. The functional importance of p40 is confirmed by the finding that anti-p40 antibodies inhibit in vitro transport. Finally, p40 shows synergy with Rab9 in terms of its ability to stimulate mannose 6-phosphate receptor transport. These data are consistent with a model in which p40 and Rab9 act together to drive the process of transport vesicle docking.	SIGNOR-253088
P35222	Q9Y4A5	1	binding	up-regulates	0.58	The beta-cat c-terminal activation domain associates with trrap/tip60 and mixed-lineage-leukemia (mll1/mll2) set1-type chromatin-modifying complexes in vitro, and we show that beta-cat promotes h3k4 trimethylation at the c-myc gene in vivo.	SIGNOR-144966
Q8WZ42	Q5VST9	1	relocalization	up-regulates quantity	0.58	Ankyrin-B is targeted to the M-line via its interaction with the C-terminal domain of the large sarcomeric protein obscurin. Obscurin is targeted to the M-line via its N-terminal interactions with myomesin and titin. This population of ankyrin-B recruits B56α, a regulatory subunit of protein phosphatase 2A, to the M-line where the phosphatase may regulate the phosphorylation status of contractile and signalling proteins.	SIGNOR-266728
P04150	P28562	1	null	up-regulates quantity	0.58	Glucocorticoids inhibit MAP kinase via increased expression and decreased degradation of MKP-1\|Both induction of MKP-1 expression and inhibition of its degradation are necessary for glucocorticoid-mediated inhibition of Erk-1/2 activation. In NIH-3T3 fibroblasts, although glucocorticoids up-regulate the MKP-1 level, they do not attenuate the proteasomal degradation of this protein and consequently they are unable to inhibit Erk-1/2 activity.	SIGNOR-253546
P15248	P31785	1	binding	up-regulates	0.58	The common gamma-chain (gamma(c)) is an indispensable subunit of the functional receptor complexes for il-4, il-7, il-9, and il-15 as well as il-2. Here we show that the gamma(c) is also shared with the il-21r complex	SIGNOR-108867
Q02763	P29353	1	binding	up-regulates activity	0.58	Our results identified a novel interaction between Tie2 with the adapter molecule ShcA and suggested that this interaction may play a role in the regulation of migration and three-dimensional organization of endothelial cells induced by angiopoietin-1. Furthermore, Tyr-1101 of Tie2 was identified as the primary binding site for the SH2 domain of ShcA.	SIGNOR-242573
P09619	P06241	1	phosphorylation	up-regulates activity	0.58	PDGF-induced phosphorylation of Tyr28 in the N-terminus of Fyn affects Fyn activation. We show here that Fyn, a member of the Src family, is phosphorylated on Tyr28 in the unique N-terminal part of the molecule after interaction with the intracellular domain of the PDGF beta-receptor. Activated Fyn furthermore undergoes autophosphorylation on Tyr30, Tyr39 and Tyr420. When Fyn mutants with Tyr28, Tyr30 or Tyr39 replaced with phenylalanine residues were transfected into NIH3T3 cells a decreased activation after PDGF stimulation was seen, suggesting a functional importance of the N-terminal tyrosine phosphorylation of Fyn.	SIGNOR-250253
O15105	Q15750	1	binding	down-regulates	0.58	Smad6 interacts with tak1 and tab1, and smad7 with tab1. The interaction of i-smads with tak1 and/or tab1 implies that several mechanisms exist underlying the repression of the tak1-p38 kinase pathway by i-smads.	SIGNOR-112645
P62993	P00519	1	binding	up-regulates	0.58	We demonstrate that bcr-abl exists in a complex with grb-2 in vivo. Binding of grb-2 to bcr-abl is mediated by the direct interaction of the grb-2 sh2 domain with a phosphorylated tyrosine, y177, within the bcr first exon.	SIGNOR-39049
P12931	P10301	1	phosphorylation	down-regulates activity	0.58	The small gtpase, r-ras, affects cell adhesion by maintaining integrin activity. Activated src oncogene phosphorylates r-ras and suppresses integrin activity. the src phosphorylation site in r-ras was tyrosine 66	SIGNOR-111189
Q9BS26	Q14643	1	binding	down-regulates activity	0.58	In this study, we found that ERp44, an ER lumenal protein of the thioredoxin family, directly interacts with the third lumenal loop of IP(3)R type 1 (IP(3)R1) and that the interaction is dependent on pH, Ca(2+) concentration, and redox state. In this study we demonstrated that ERp44 directly interacts with the L3V domain of IP3R1, thereby inhibiting its channel activity.	SIGNOR-261046
P09619	P20936	1	binding	up-regulates	0.58	The gtpase activating protein (gap) of ras binds only to beta-receptors / we have previously shown that the binding site for gtpase activating protein of ras (rasgap) in the pdgf beta-receptor, tyr771, is phosphorylated to a much lower extent in the heterodimeric configuration of pdgf alpha- and beta-receptors, compared to the pdgf beta-receptor homodimer. / the decreased recruitment of the rasgap to the receptor leads to prolonged activation of the ras/map kinase pathway	SIGNOR-115843
P32745	P63096	1	binding	up-regulates activity	0.58	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-256677
Q9NRI5	Q9GZM8	1	binding	up-regulates activity	0.58	Disrupted-In-Schizophrenia 1 (DISC1) is a candidate gene for susceptibility to schizophrenia. DISC1 is reported to interact with NudE-like (NUDEL), which forms a complex with lissencephaly-1 (LIS1) and 14-3-3ε. 14-3-3ε is involved in the proper localization of NUDEL and LIS1 in axons. the association with NUDEL and LIS1 supports the notion that DISC1 contributes to the neuronal development and morphology	SIGNOR-252162
P12931	Q13761	1	phosphorylation	down-regulates activity	0.58	In this study, we provide evidence that Src phosphorylates RUNX3 at multiple tyrosine residues.\|Our finding that Src inactivates RUNX3 by cytoplasmic sequestration in gastric cancer and breast cancer suggests that the inactivation of RUNX3 may be a key function of oncogenic kinases.	SIGNOR-278199
O43541	Q15797	2	binding	down-regulates	0.579	Smad6 also inhibits bmp signaling by forming a complex with smad1 and by interfering with complex formation between smad1 and smad4	SIGNOR-103621
P06493	P04637	1	phosphorylation	up-regulates activity	0.579	The N-terminus of E2F1 can interact directly with a region towards the C-terminus of p53, resulting in increased nuclear retention of p53 and p53-mediated transcription and apoptosis. This is inhibited by competition between p53 and cyclin A at the binding site within E2F19,10. The interaction between p53 and E2F1 is enhanced by phosphorylation of p53 on Ser315, a residue within the E2F1 binding region that is phosphorylated by cell cycle kinases such as cdk1, cdk2, cdk9 and Aurora kinase A	SIGNOR-167779
P27361	P17480	1	phosphorylation	down-regulates	0.579	Erk1/2 was found to phosphorylate the architectural transcription factor ubf at amino acids 117 and 201 within hmg boxes 1 and 2, preventing their interaction with dna	SIGNOR-112817
Q9NYY3	Q9HC77	1	phosphorylation	up-regulates	0.579	Plk2 phosphorylates the s589 and s595 residues of cpap in vitro and in vivo. This phosphorylation is critical for procentriole formation during the centrosome cycle.	SIGNOR-165999
O00141	P49815	1	phosphorylation	down-regulates activity	0.579	SGK1, which is activated by PDK1, contributes to the maintenance of residual mTORC1 activity through direct phosphorylation and inhibition of TSC2.	SIGNOR-277266
Q00987	Q13761	1	ubiquitination	down-regulates quantity by destabilization	0.579	RUNX3 protein is ubiquitinated by MDM2 at Lys-94 and Lys-148.\|RUNX3 protein is ubiquitinated by MDM2 at Lys 94 and Lys 148.\|MDM2 suppresses the transcriptional activity of RUNX3.	SIGNOR-278557
P61328	Q14524	1	binding	down-regulates activity	0.579	Sodium channel fast inactivation is modulated by alpha subunit interaction with a family of cytoplasmic proteins termed fibroblast growth factor homologous factors (FHFs). In this paper, we report that all A-type FHFs exert rapid onset long-term inactivation on Nav1.6 and other sodium channels.	SIGNOR-253416
P49841	Q13144	1	phosphorylation	down-regulates activity	0.579	The largest (epsilon) subunit of eIF2B is a substrate for glycogen synthase kinase (GSK)-3 in vitro, and phosphorylation by GSK3 inhibits the activity of eIF2B. The site of phosphorylation has previously been identified as Ser(535).	SIGNOR-251236
P78527	P15927	1	phosphorylation	down-regulates activity	0.579	We showed previously that UV irradiation increases phosphorylation of the p34 subunit of human replication protein A (RPA) and that this hyperphosphorylation correlated with loss of activity of the DNA replication complex. \| we detected phosphorylation of the RPA complex by DNA-PK on RPA-p34 sites Ser-23, Ser-29, and Ser-11, -12, or -13	SIGNOR-248981

Q9UH77

Q96J92

1

binding

down-regulates quantity by destabilization

0.585

Here, we found that KLHL3 interacted with Cullin3 and WNK4, induced WNK4 ubiquitination, and reduced the WNK4 protein level. The reduced interaction of KLHL3 and WNK4 by PHAII-causing mutations in either protein reduced the ubiquitination of WNK4, resulting in an increased level of WNK4 protein.

SIGNOR-272105

Q5SGD2

O43318

1

dephosphorylation

down-regulates activity

0.585

Co-immunoprecipitation experiments indicated that PP2Cepsilon associates stably with TAK1 and attenuates the binding of TAK1 to MKK4 or MKK6.|PP2Cepsilon dephosphorylated TAK1 in vitro.

SIGNOR-277114

P00519

Q00535

1

phosphorylation

up-regulates activity

0.585

Phosphorylation of Cdk5 by c-Abl occurs on tyrosine 15 (Y15), which is stimulatory for p35/Cdk5 kinase activity.

SIGNOR-245288

P15391

P27986

1

binding

up-regulates activity

0.585

CD19 has an extracellular region containing two C2-type Ig-like domains and a cytoplasmic region of ~240 amino acids with 9 conserved tyrosine residues24. Lyn, a Src-family protein tyrosine kinase member, is the dominant kinase that phosphorylates CD19 upon stimulation. Once tyrosyl-phosphorylated, CD19 serves as a membrane-bound adaptor protein for Src homology 2-containing signaling molecules such as Lyn, Vav, and phosphatidylinositol 3-kinase, which further mediate downstream activation cascades.

SIGNOR-242900

P12931

O15530

1

phosphorylation

up-regulates activity

0.585

Using site-directed mutants, we show that, although phosphorylation on tyr-373/376 is important for pdk1 activity, phosphorylation on tyr-9 has no effect on the activity of the kinase. Both of these residues can be phosphorylated by v-src tyrosine kinase in vitro, and co-expression of v-src leads to tyrosine phosphorylation and activation of pdk1.

SIGNOR-109533

P35348

P50148

1

binding

up-regulates activity

0.585

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-257084

P06493

Q8NHV4

1

phosphorylation

up-regulates activity

0.585

Here we report that the function of Nedd1 is regulated by Cdk1 and Plk1. During mitosis, Nedd1 is firstly phosphorylated at T550 by Cdk1, which creates a binding site for the polo-box domain of Plk1. Then, Nedd1 is further phosphorylated by Plk1 at four sites: T382, S397, S637 and S426. The sequential phosphorylation of Nedd1 by Cdk1 and Plk1 promotes its interaction with gamma-tubulin for targeting the gammaTuRC to the centrosome and is important for spindle formation.

SIGNOR-272973

Q99985

O60462

1

binding

up-regulates

0.585

Our experiments establish that small peptides containing the consensus decd sequence of sperm fertilinbeta bind specifically to an alpha6beta1 integrin receptor on the egg membrane. We conclude that fertilinbeta binds directly to the alpha6beta1 integrin on the egg surface and this partnership mediates sperm-egg fusion.

SIGNOR-147564

Q8IYT4

Q9BVA0

1

binding

up-regulates activity

0.585

Katanin, a heterodimeric microtubule-severing ATPase, is found localized at mitotic spindle poles. In this paper we demonstrate that human p60 katanin and the C-terminal domain of human p80 katanin both bind microtubules in vitro. Association of these two proteins results in an increased microtubule affinity and increased microtubule-severing activity in vitro. Association of these subunits in transfected HeLa cells increases microtubule disassembly activity and targeting to spindle poles.

SIGNOR-267180

O60716

P63000

1

binding

up-regulates

0.585

We demonstrate that p120-catenin participates in the stimulation of rac1 activity, binding directly to this protein. In addition we show that vav2 also binds to p120-catenin and is required for rac1 activation and for beta-catenin translocation to the nucleus.Vav2 And rac1 association with p120-catenin was modulated by phosphorylation of this protein, which was stimulated upon serine/threonine phosphorylation by ck1 and inhibited by tyrosine phosphorylation by src or fyn

SIGNOR-198938

P25100

P50148

1

binding

up-regulates activity

0.585

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-257080

Q9Y490

P26010

1

binding

up-regulates activity

0.585

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

SIGNOR-257633

O43283

O14733

1

phosphorylation

up-regulates

0.584

Lzk directly phosphorylated and activated mkk7.

SIGNOR-112349

Q9Y2E6

Q9UHD2

1

ubiquitination

down-regulates

0.584

Nlrp4 negatively regulates type i interferon signaling by targeting the kinase tbk1 for degradation via the ubiquitin ligase dtx4

SIGNOR-71565

O14965

Q99661

1

phosphorylation

down-regulates activity

0.584

In addition, we found that MCAK localization at spindle poles was regulated through another Aurora A phosphorylation site (S719), which positively enhances bipolar spindle formation.

SIGNOR-279139

Q13418

O14974

1

phosphorylation

down-regulates activity

0.584

MYPT1 was phosphorylated by ILK and phosphorylation sites in the N- and C-terminal fragments of MYPT1 were detected. From sequence analyses, three sites were identified: a primary site at Thr(709), and two other sites at Thr(695) and Thr(495). ILK produced an intermediate level of inhibition

SIGNOR-262884

Q6UXZ4

P43146

1

binding

down-regulates activity

0.584

In the presence of netrin-1, UNC5 co-immuno-precipitates with DCC, suggesting the formation of a ternary complex of netrin-1 with ecto-domains of DCC and UNC5. DCC binding to netrin-1 alone leads to axon attraction. Importantly, DCC has the ability to switch the netrin-1-mediated responses from attraction to repulsion when another receptor UNC5 co-exists. DCC binding to netrin-1 alone leads to axon attraction. Importantly, DCC has the ability to switch the netrin-1-mediated responses from attraction to repulsion when another receptor UNC5 co-exists.

SIGNOR-268167

O14640

P63000

1

binding

up-regulates activity

0.584

B-catenin-independent wnt signaling can activate rho family gtpases through at least two mechanisms: (1) direct activation of rac1 by dvl;and (2) activation of rhoa via dvl-associated activator of morphogenesis-1 (daam1), possibly through the weak-similarity guaninenucleotide exchange factor (wgef)1.

SIGNOR-185274

P15976

P56524

1

relocalization

up-regulates activity

0.584

GATA1 is a new substrate of p21-activated kinase 5 (PAK5), which is phosphorylated on serine 161 and 187 (S161 and S187). GATA1 recruits HDAC3/4 to E-cadherin promoter, which is reduced by GATA1 S161A S187A mutant. These data indicate that phosphorylated GATA1 recruits more HDAC3/4 to promote transcriptional repression of E-cadherin, leading to the EMT of breast cancer cells.

SIGNOR-275665

Q07812

P21796

1

binding

up-regulates activity

0.584

The recombinant pro-apoptotic proteins Bax and Bak accelerate the opening of VDAC

SIGNOR-249613

O43663

Q02224

1

binding

up-regulates activity

0.584

These data indicate that PRC1 binds to KIF4, MKLP1 and CENP-E during late mitosis; however, it apparently does not interact simultaneously with more than one of these motor proteins.

SIGNOR-265990

P10721

Q14451

1

binding

up-regulates activity

0.584

We furthermore demonstrate that the adapter protein Grb2 is a specific binding partner for both phosphorylated Tyr-703 and phosphorylated Tyr-936, whereas the adapter protein Grb7 binds selectively to phosphorylated Tyr-936.

SIGNOR-248291

P49137

P11831

1

phosphorylation

up-regulates

0.584

Neverthless, some transcription factors, such as e47, er81, srf and creb are also phosphorylated by mk2

SIGNOR-166640

Q15831

P57059

1

phosphorylation

up-regulates

0.584

Lkb1 is a master kinase that activates 13 kinases of the ampk subfamily, including mark/par-1we recently demonstrated that the lkb1 tumour suppressor kinase, in complex with the pseudokinase strad and the scaffolding protein mo25, phosphorylates and activates amp-activated protein kinase (ampk). A total of 12 human kinases (nuak1, nuak2, brsk1, brsk2, qik, qsk, sik, mark1, mark2, mark3, mark4 and melk) are related to ampk. Here we demonstrate that lkb1 can phosphorylate the t-loop of all the members of this subfamily, apart from melk, increasing their activity >50-fold

SIGNOR-122784

O75925

Q9UPW6

1

sumoylation

down-regulates activity

0.583

We found that SATB2 differs from the closely related thymocyte-specific protein SATB1 by modifications of two lysines with the small ubiquitive related modifier (SUMO), which are augmented specifically by the SUMO E3 ligase PIAS1.

SIGNOR-269112

P43246

P54132

1

binding

up-regulates

0.583

We show that the recombinant hmsh2/6 protein complex stimulated the ability of the bloom's syndrome gene product, blm, to process holliday junctions in vitro

SIGNOR-123699

Q3KR16

P61586

1

guanine nucleotide exchange factor

up-regulates activity

0.583

We therefore developed a screening-compatible live-cell imaging assay, using FRET-based biosensors for the prototype GTPases RHOA, RAC1 and CDC4215,19,20 (Extended Data Fig. 2 and Supplementary Note 1)|We found catalytic activities for 45/75 RhoGEFs and 48/63 RhoGAPs| Our data thus not only reveal extensive promiscuity among regulators, but also that the inactivating RhoGAPs are less selective than the activating RhoGEFs (p-value=0.02)(Supplementary Table 2).

SIGNOR-260567

P53350

O15392

1

phosphorylation

up-regulates

0.583

Thus, we conclude that plk1-mediated phosphorylation of sur at ser20 is critical for accurate chromosome segregation|SUR (survivin)

SIGNOR-170460

P04637

P11413

1

binding

down-regulates activity

0.583

The p53 protein binds to glucose-6-phosphate dehydrogenase (G6PD), the first and rate-limiting enzyme of the PPP, and prevents the formation of the active dimer.

SIGNOR-267468

Q13145

Q13467

1

binding

up-regulates

0.583

These data together suggest that bambi may form a ternary coreceptor complex with fzd5 and lrp6

SIGNOR-23040

Q96JJ3

P63000

1

guanine nucleotide exchange factor

up-regulates activity

0.583

We found in this study that AUTS2 is involved in Rac1 activation via P-Rex1 and the Elmo2/Dock180 complex, but not STEF or Tiam1, for the lamellipodia formation in N1E-115 cells. However, the enhancement of neurite elongation in primary neurons by AUTS2 expression is specifically mediated by the Elmo2/Dock180 complex. These results suggested that several Rac-GEFs differentially or cooperatively participate in Rac1 activation to promote neuronal migration and neurite outgrowth.

SIGNOR-266821

Q9UHD9

Q13148

1

binding

down-regulates quantity by destabilization

0.583

Here, we describe a high affinity interaction between UBQLN2 and TDP-43 and demonstrate that overexpression of both UBQLN2 and TDP-43 reduces levels of both exogenous and endogenous TDP-43 in human H4 cells.|Consequently, these data suggest that UBQLN2 enhances the clearance of TDP-43

SIGNOR-262112

P08311

P25116

1

cleavage

down-regulates activity

0.583

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.|Protease-activated receptors (PARs) mediate cell activation after proteolytic cleavage of their extracellular amino terminus.|Plasmin, calpain and leukocyte elastase, cathepsin G, and proteinase 3 cleaved at multiple sites and would be expected to disable PAR1 by cleaving COOH-terminal to the activation site.

SIGNOR-263564

P28482

P06239

1

phosphorylation

up-regulates activity

0.583

Phosphorylation at Ser-59 (or alternatively, its mutation to Glu) reverses the inhibition and allows interaction of the p56lck SH2 domain with p62.|phosphotyrosine-independent binding of p62 to the p56lck SH2 domain appears to provide an alternative pathway for p56lck signaling that is regulated by Ser-59 phosphorylation.

SIGNOR-249412

Q6ZMZ0

Q9NWZ5

1

ubiquitination

down-regulates quantity by destabilization

0.583

We demonstrated that both UbcH7 and UbcH8 bind to full-length NKLAM. We demonstrated decreased protein expression and enhanced ubiquitination of URKL-1 in the presence of NKLAM. These data indicate that NKLAM is a RING finger protein that binds Ubcs and has as one of its substrates, URKL-1, thus defining this cytolytic protein as an E3 ubiquitin ligase.

SIGNOR-271590

P27348

Q14814

1

binding

up-regulates

0.583

14-3-3tau associates with and activates the mef2d transcription factor during muscle cell differentiation.

SIGNOR-109139

Q13469

Q14814

1

binding

up-regulates

0.583

Upon dephosphorylation by calcineurin, nfatc2, also referred to as nfatp/nfat1, translocates to the nucleus where it directly associates with mef2a and -d. Nfatc2 stimulates mef2-dependent transcription by facilitating recruitment of the p300 coactivator to mef2-response elements.

SIGNOR-117589

P41134

Q99081

1

binding

down-regulates activity

0.583

All three Ids bound with high affinity to E proteins .Each Id was able to disrupt the ability of E protein-MyoD complexes to transactivate from a muscle creatine kinase reporter construct in vivo.

SIGNOR-241104

P62993

Q92835

1

binding

up-regulates activity

0.583

An adaptor protein Dok-3 mediates the suppressive function of LYN. The Dok-3 phosphorylated by LYN upon BCR stimulation forms a complex with GRB2, which allows it to enter into the signalosome and associate with activation of SHIP protein. This translocation facilitates the efficient inhibition of PLCc2 and SYK from activation, subsequently resulting in the suppression of downstream Ca2+ signaling.

SIGNOR-268449

P12931

P08069

1

phosphorylation

up-regulates activity

0.582

The insulin-like growth factor type I (IGF-I) receptor can become tyrosine phosphorylated and enzymatically activated either in response to ligand or because of the activity of the Src tyrosine kinaseWe mapped the sites of IGF-I receptor autophosphorylation to peptides representing three different receptor domains: tyrosines 943 and 950 in the juxtamembrane region; tyrosines 1131, 1135, and 1136 within the kinase domain; and tyrosine 1316 in the carboxyl-terminal domain.

SIGNOR-247193

P25116

P50148

1

binding

up-regulates activity

0.582

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-257219

O14733

P53779

1

phosphorylation

up-regulates

0.582

Two mapkks, sek1 and mkk7, synergistically activate jnk. Sek1 prefers the tyr-185 residue, and mkk7 prefers the thr-183 residue (17, 19).

SIGNOR-137609

O95819

O43318

1

binding

up-regulates

0.582

The existence of an at least trimolecular complex consisting of nik, tak1, and ikk2, although the precise sequence of activation as well as the possible location of the kinases within the signalosome remains to be elucidated.

SIGNOR-77404

Q14669

Q8N726

1

ubiquitination

down-regulates quantity by destabilization

0.582

ULF interacts with ARF both in vitro and in vivo and promotes the lysine-independent ubiquitylation and degradation of ARF.

SIGNOR-266781

O95295

P60880

1

binding

up-regulates activity

0.582

In the present study, we used yeast two-hybrid analysis to identify a new binding partner of torsinA, the SNARE-associated protein snapin. We have reported that snapin shows a robust interaction with wild type and mutant torsinA. we have demonstrated that this portion of torsinA and/or the adjacent linker region has the additional role of recruiting snapin. we found that snapin, which binds SNAP-25 (synaptosome-associated protein of 25,000 Da) and enhances the association of the SNARE complex with synaptotagmin, is an interacting partner for both wild type and mutant torsinA.

SIGNOR-261171

P45983

P10415

1

phosphorylation

down-regulates

0.582

G(2)/m-phase cells proved more susceptible to death signals, and phosphorylation of bcl-2 appeared to be responsible, as a ser70ala substitution restored resistance to apoptosis. We noted that ask1 and jnk1 were normally activated at g(2)/m phase, and jnk was capable of phosphorylating bcl-2..

SIGNOR-72361

P00519

Q9UPY6

1

phosphorylation

up-regulates activity

0.582

WAVE3-Abl interaction promotes the tyrosine phosphorylation of WAVE3 by Abl, and STI-571, a specific inhibitor of Abl kinase activity, abrogates the Abl-mediated phosphorylation of WAVE3.

SIGNOR-259077

Q9Y297

Q15653

1

binding

down-regulates quantity by destabilization

0.582

Interaction with beta-TrCP is also necessary for ubiquitination of IkappaBbeta upon stimulation of cells, and deletion of the F-box in beta-TrCP abolishes its ability to ubiquitinate IkappaBbeta. Therefore, these results indicate that beta-TrCP plays a critical role in the activation of NF-kappaB by assembling the ubiquitin ligase complex for both phosphorylated IkappaBalpha and IkappaBbeta.β-TrCP recognizes IκBα phosphorylated at Ser-32 and Ser-36 through its WD40 domain, whereas the F-box motif recruits additional proteins including Skp1 and Cullin to form the Skp1-cullin-F-box (SCF) ubiquitin ligase complex

SIGNOR-272554

Q15311

P63000

1

gtpase-activating protein

down-regulates activity

0.582

We therefore developed a screening-compatible live-cell imaging assay, using FRET-based biosensors for the prototype GTPases RHOA, RAC1 and CDC4215,19,20 (Extended Data Fig. 2 and Supplementary Note 1)|We found catalytic activities for 45/75 RhoGEFs and 48/63 RhoGAPs| Our data thus not only reveal extensive promiscuity among regulators, but also that the inactivating RhoGAPs are less selective than the activating RhoGEFs (p-value=0.02)(Supplementary Table 2).

SIGNOR-260513

Q13216

Q03468

1

ubiquitination

down-regulates quantity by destabilization

0.582

We have previously shown that CSA is a subunit of an E3 ubiquitin ligase complex. Here we demonstrate that CSB is a substrate of this ligase: Following UV irradiation, CSB is degraded at a late stage of the repair process in a proteasome- and CSA-dependent manner.

SIGNOR-271406

Q5VWK5

P29597

1

binding

up-regulates

0.582

Il-23 activates the same jak-stat signaling molecules as il-12: jak2, tyk2, and stat1, -3, -4, and -5, but stat4 activation is substantially weaker and different dna-binding stat complexes form in response to il-23 compared with il-12.

SIGNOR-87841

P19793

Q03181

1

binding

up-regulates

0.582

Although the three ppar subtypes are closely related and bind to similar dna response elements as heterodimers with the 9-cis retinoic acid receptor rxr, each subserves a distinct physiology

SIGNOR-105442

Q12913

P09619

1

dephosphorylation

down-regulates activity

0.582

Primary sequence determinants responsible for site-selective dephosphorylation of the PDGF beta-receptor by the receptor-like protein tyrosine phosphatase DEP-1|DEP-1 dephosphorylation of original and chimeric phospho-peptides spanning the preferred pY1021

SIGNOR-248704

P04637

P54278

1

transcriptional regulation

up-regulates quantity

0.582

.... numerous potentially novel targets, including the DNA mismatch repair genes MLH1 and PMS2. Both of these genes were determined to be responsive to DNA damage and p53 activation in normal human fibroblasts, and have p53-response elements within their first intron.

SIGNOR-257604

Q13153

Q02750

1

phosphorylation

up-regulates activity

0.582

We find that adhesion to fibronectin induces pak1-dependent phosphorylation of mek1 on s298 and that this phosphorylation is necessary for efficient activation of mek1 and subsequent mapk activation.

SIGNOR-236002

P30874

P63096

1

binding

up-regulates activity

0.582

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-256684

P53779

P05067

1

phosphorylation

up-regulates

0.582

Phosphorylation of amyloid precursor protein at threonine 668 is essential for its copper-responsive trafficking in sh-sy5y neuroblastoma cells. is regulated by jnk3 via phosphorylation of app at thr668

SIGNOR-204671

P31749

P04406

1

phosphorylation

down-regulates activity

0.582

GAPDH is phosphorylated by protein kinase B (AKT) on T237, which prevents GAPDH nuclear translocation and suppresses GAPDH mediated apoptosis.|GAPDH is phosphorylated by protein kinase B (AKT) on T237, which prevents GAPDH nuclear translocation and suppresses GAPDH-mediated apoptosis ( ).

SIGNOR-280174

O75385

Q7Z3C6

1

phosphorylation

up-regulates activity

0.582

Src phosphorylates mATG9 at Tyr8 to maintain its endocytic and constitutive trafficking in unstressed conditions. In response to starvation, phosphorylation of mATG9 at Tyr8 by Src and at Ser14 by ULK1 functionally cooperate to promote interactions between mATG9 and the AP1/2 complex, leading to redistribution of mATG9 from the plasma membrane and juxta-nuclear region to the peripheral pool for autophagy initiation.

SIGNOR-266369

Q9Y6F9

O75197

1

binding

up-regulates

0.581

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-131894

Q53QZ3

P63000

1

gtpase-activating protein

down-regulates activity

0.581

We therefore developed a screening-compatible live-cell imaging assay, using FRET-based biosensors for the prototype GTPases RHOA, RAC1 and CDC4215,19,20 (Extended Data Fig. 2 and Supplementary Note 1)|We found catalytic activities for 45/75 RhoGEFs and 48/63 RhoGAPs| Our data thus not only reveal extensive promiscuity among regulators, but also that the inactivating RhoGAPs are less selective than the activating RhoGEFs (p-value=0.02)(Supplementary Table 2).

SIGNOR-260470

P0DP24

Q08209

1

binding

up-regulates

0.581

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

SIGNOR-266327

P17612

P16220

1

phosphorylation

up-regulates activity

0.581

Using a combination of in vitro explant assays, mutant analysis and gene delivery into mouse embryos cultured ex vivo, we demonstrate that adenylyl cyclase signalling via PKA and its target transcription factor CREB are required for WNT-directed myogenic gene expression.

SIGNOR-131307

P50613

P06493

1

phosphorylation

up-regulates

0.581

The mo15 gene encodes the catalytic subunit of a protein kinase that activates cdc2 and other cyclin-dependent kinases (cdks) through phosphorylation of thr161 and its homologues

SIGNOR-38307

P23467

P33151

1

dephosphorylation

up-regulates activity

0.581

Because we had shown previously that VE-PTP supports VE-cadherin function when exogenously expressed in transfected cells, we expected it to be expressed at endothelial cell contacts.|Indeed, tyrosine phosphorylation of VE-cadherin is reduced by VE-PTP in COS-7 and CHO cells.

SIGNOR-277131

P68400

P25963

1

phosphorylation

down-regulates

0.581

Casein kinase ii phosphorylates i kappa b alpha at s-283, s-289, s-293, and t-291 and is required for its degradation.

SIGNOR-40502

O75509

Q15628

1

binding

up-regulates

0.581

Dr6 interacts with tradd

SIGNOR-100184

Q96PM5

Q9Y253

1

monoubiquitination

down-regulates activity

0.581

Pirh2 E3 ubiquitin ligase monoubiquitinates DNA polymerase eta to suppress translesion DNA synthesis. Specifically, we show that Pirh2, a target of the p53 tumor suppressor, monoubiquitinates PolH at one of multiple lysine residues.we show that monoubiquitination of PolH alters the ability of PolH to translocate to replication foci for translesion DNA synthesis of UV-induced DNA lesions.These results suggest that Pirh2 monoubiquitinates PolH at one of the four lysine residues (K682, K686, K694, and K709).

SIGNOR-272733

P67775

Q08999

1

dephosphorylation

up-regulates

0.581

Pocket protein family consists of the retinoblastoma tumor suppressor protein (prb) and the functionally and structurally related proteins p107 and p130./dephosphorylation of p130 and p107 in cell extracts is inhibited by concentrations of okadaic acid known to inhibit pp2a, but not pp1. Finally, the pp2a catalytic subunit pp2a/c) specifically interacts with both p130 and p107 / the cell cycle repressor activity of pocket proteins is inactivated by cdk mediated phosphorylation.

SIGNOR-129752

Q96SW2

Q9UKT9

1

ubiquitination

down-regulates quantity by destabilization

0.581

IMiD compounds cause selective ubiquitination and degradation of IKZF1 in CD34+ cells by the CRBN E3 ubiquitin ligase.

SIGNOR-272319

Q06187

P19174

1

phosphorylation

up-regulates activity

0.581

Then, BTK and ITK are activated by Src kinases and proceed to phosphorylate the lipase PLCgamma2 / PLCgamma1, which cleaves PIP2 in the plasma membrane and generates the secondary messengers IP3 and DAG.

SIGNOR-279444

P06493

Q9BZB8

1

phosphorylation

up-regulates activity

0.581

Combined, our results suggest that XGef is involved in XRINGO and CDK1 mediated activation of CPEB and that an XGef, XRINGO, ERK2, and CPEB complex forms in ovo to facilitate this process.|Notably, specific inhibition of XRINGO and CDK1 activity in CPEB phosphorylation-competent extracts completely blocks phosphorylation of CPEB, which suggests that XRINGO and CDK1 directly phosphorylates CPEB.

SIGNOR-280205

Q5S007

O14966

1

phosphorylation

up-regulates activity

0.581

In an attempt to mimic phosphorylation of Rab29 by LRRK2, we mutated the phosphorylation sites to Glu and observed that the Rab29[T71E,S72E] mutant failed to activate LRRK2 (Fig\u00a0 xref B).|To test whether phosphorylation of Rab29 at Thr71 and Ser72 by LRRK2 was required for activation of LRRK2, we mutated these sites both to Ala.

SIGNOR-279474

Q86T82

P20248

1

deubiquitination

up-regulates quantity by stabilization

0.581

USP37 Binds, Deubiquitinates, and Stabilizes Cyclin A

SIGNOR-265052

O43182

P61586

1

gtpase-activating protein

down-regulates activity

0.581

We therefore developed a screening-compatible live-cell imaging assay, using FRET-based biosensors for the prototype GTPases RHOA, RAC1 and CDC4215,19,20 (Extended Data Fig. 2 and Supplementary Note 1)|We found catalytic activities for 45/75 RhoGEFs and 48/63 RhoGAPs| Our data thus not only reveal extensive promiscuity among regulators, but also that the inactivating RhoGAPs are less selective than the activating RhoGEFs (p-value=0.02)(Supplementary Table 2).

SIGNOR-260462

P61457

P35680

1

binding

up-regulates activity

0.581

Overexpression in a human kidney cell line showed that wild-type PCBD1 binds HNF1B to costimulate the FXYD2 promoter, the activity of which is instrumental in Mg(2+) reabsorption in the DCT.

SIGNOR-254910

P51151

Q7Z6M1

1

null

up-regulates activity

0.581

P40 is a very potent transport factor in that the pure, recombinant protein can stimulate, significantly, an in vitro transport assay that measures transport of mannose 6-phosphate receptors from endosomes to the trans-Golgi network. The functional importance of p40 is confirmed by the finding that anti-p40 antibodies inhibit in vitro transport. Finally, p40 shows synergy with Rab9 in terms of its ability to stimulate mannose 6-phosphate receptor transport. These data are consistent with a model in which p40 and Rab9 act together to drive the process of transport vesicle docking.

SIGNOR-253088

P35222

Q9Y4A5

1

binding

up-regulates

0.58

The beta-cat c-terminal activation domain associates with trrap/tip60 and mixed-lineage-leukemia (mll1/mll2) set1-type chromatin-modifying complexes in vitro, and we show that beta-cat promotes h3k4 trimethylation at the c-myc gene in vivo.

SIGNOR-144966

Q8WZ42

Q5VST9

1

relocalization

up-regulates quantity

0.58

Ankyrin-B is targeted to the M-line via its interaction with the C-terminal domain of the large sarcomeric protein obscurin. Obscurin is targeted to the M-line via its N-terminal interactions with myomesin and titin. This population of ankyrin-B recruits B56α, a regulatory subunit of protein phosphatase 2A, to the M-line where the phosphatase may regulate the phosphorylation status of contractile and signalling proteins.

SIGNOR-266728

P04150

P28562

1

null

up-regulates quantity

0.58

Glucocorticoids inhibit MAP kinase via increased expression and decreased degradation of MKP-1|Both induction of MKP-1 expression and inhibition of its degradation are necessary for glucocorticoid-mediated inhibition of Erk-1/2 activation. In NIH-3T3 fibroblasts, although glucocorticoids up-regulate the MKP-1 level, they do not attenuate the proteasomal degradation of this protein and consequently they are unable to inhibit Erk-1/2 activity.

SIGNOR-253546

P15248

P31785

1

binding

up-regulates

0.58

The common gamma-chain (gamma(c)) is an indispensable subunit of the functional receptor complexes for il-4, il-7, il-9, and il-15 as well as il-2. Here we show that the gamma(c) is also shared with the il-21r complex

SIGNOR-108867

Q02763

P29353

1

binding

up-regulates activity

0.58

Our results identified a novel interaction between Tie2 with the adapter molecule ShcA and suggested that this interaction may play a role in the regulation of migration and three-dimensional organization of endothelial cells induced by angiopoietin-1. Furthermore, Tyr-1101 of Tie2 was identified as the primary binding site for the SH2 domain of ShcA.

SIGNOR-242573

P09619

P06241

1

phosphorylation

up-regulates activity

0.58

PDGF-induced phosphorylation of Tyr28 in the N-terminus of Fyn affects Fyn activation. We show here that Fyn, a member of the Src family, is phosphorylated on Tyr28 in the unique N-terminal part of the molecule after interaction with the intracellular domain of the PDGF beta-receptor. Activated Fyn furthermore undergoes autophosphorylation on Tyr30, Tyr39 and Tyr420. When Fyn mutants with Tyr28, Tyr30 or Tyr39 replaced with phenylalanine residues were transfected into NIH3T3 cells a decreased activation after PDGF stimulation was seen, suggesting a functional importance of the N-terminal tyrosine phosphorylation of Fyn.

SIGNOR-250253

O15105

Q15750

1

binding

down-regulates

0.58

Smad6 interacts with tak1 and tab1, and smad7 with tab1. The interaction of i-smads with tak1 and/or tab1 implies that several mechanisms exist underlying the repression of the tak1-p38 kinase pathway by i-smads.

SIGNOR-112645

P62993

P00519

1

binding

up-regulates

0.58

We demonstrate that bcr-abl exists in a complex with grb-2 in vivo. Binding of grb-2 to bcr-abl is mediated by the direct interaction of the grb-2 sh2 domain with a phosphorylated tyrosine, y177, within the bcr first exon.

SIGNOR-39049

P12931

P10301

1

phosphorylation

down-regulates activity

0.58

The small gtpase, r-ras, affects cell adhesion by maintaining integrin activity. Activated src oncogene phosphorylates r-ras and suppresses integrin activity. the src phosphorylation site in r-ras was tyrosine 66

SIGNOR-111189

Q9BS26

Q14643

1

binding

down-regulates activity

0.58

In this study, we found that ERp44, an ER lumenal protein of the thioredoxin family, directly interacts with the third lumenal loop of IP(3)R type 1 (IP(3)R1) and that the interaction is dependent on pH, Ca(2+) concentration, and redox state. In this study we demonstrated that ERp44 directly interacts with the L3V domain of IP3R1, thereby inhibiting its channel activity.

SIGNOR-261046

P09619

P20936

1

binding

up-regulates

0.58

The gtpase activating protein (gap) of ras binds only to beta-receptors / we have previously shown that the binding site for gtpase activating protein of ras (rasgap) in the pdgf beta-receptor, tyr771, is phosphorylated to a much lower extent in the heterodimeric configuration of pdgf alpha- and beta-receptors, compared to the pdgf beta-receptor homodimer. / the decreased recruitment of the rasgap to the receptor leads to prolonged activation of the ras/map kinase pathway

SIGNOR-115843

P32745

P63096

1

binding

up-regulates activity

0.58

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-256677

Q9NRI5

Q9GZM8

1

binding

up-regulates activity

0.58

Disrupted-In-Schizophrenia 1 (DISC1) is a candidate gene for susceptibility to schizophrenia. DISC1 is reported to interact with NudE-like (NUDEL), which forms a complex with lissencephaly-1 (LIS1) and 14-3-3ε. 14-3-3ε is involved in the proper localization of NUDEL and LIS1 in axons. the association with NUDEL and LIS1 supports the notion that DISC1 contributes to the neuronal development and morphology

SIGNOR-252162

P12931

Q13761

1

phosphorylation

down-regulates activity

0.58

In this study, we provide evidence that Src phosphorylates RUNX3 at multiple tyrosine residues.|Our finding that Src inactivates RUNX3 by cytoplasmic sequestration in gastric cancer and breast cancer suggests that the inactivation of RUNX3 may be a key function of oncogenic kinases.

SIGNOR-278199

O43541

Q15797

2

binding

down-regulates

0.579

Smad6 also inhibits bmp signaling by forming a complex with smad1 and by interfering with complex formation between smad1 and smad4

SIGNOR-103621

P06493

P04637

1

phosphorylation

up-regulates activity

0.579

The N-terminus of E2F1 can interact directly with a region towards the C-terminus of p53, resulting in increased nuclear retention of p53 and p53-mediated transcription and apoptosis. This is inhibited by competition between p53 and cyclin A at the binding site within E2F19,10. The interaction between p53 and E2F1 is enhanced by phosphorylation of p53 on Ser315, a residue within the E2F1 binding region that is phosphorylated by cell cycle kinases such as cdk1, cdk2, cdk9 and Aurora kinase A

SIGNOR-167779

P27361

P17480

1

phosphorylation

down-regulates

0.579

Erk1/2 was found to phosphorylate the architectural transcription factor ubf at amino acids 117 and 201 within hmg boxes 1 and 2, preventing their interaction with dna

SIGNOR-112817

Q9NYY3

Q9HC77

1

phosphorylation

up-regulates

0.579

Plk2 phosphorylates the s589 and s595 residues of cpap in vitro and in vivo. This phosphorylation is critical for procentriole formation during the centrosome cycle.

SIGNOR-165999

O00141

P49815

1

phosphorylation

down-regulates activity

0.579

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

SIGNOR-277266

Q00987

Q13761

1

ubiquitination

down-regulates quantity by destabilization

0.579

RUNX3 protein is ubiquitinated by MDM2 at Lys-94 and Lys-148.|RUNX3 protein is ubiquitinated by MDM2 at Lys 94 and Lys 148.|MDM2 suppresses the transcriptional activity of RUNX3.

SIGNOR-278557

P61328

Q14524

1

binding

down-regulates activity

0.579

Sodium channel fast inactivation is modulated by alpha subunit interaction with a family of cytoplasmic proteins termed fibroblast growth factor homologous factors (FHFs). In this paper, we report that all A-type FHFs exert rapid onset long-term inactivation on Nav1.6 and other sodium channels.

SIGNOR-253416

P49841

Q13144

1

phosphorylation

down-regulates activity

0.579

The largest (epsilon) subunit of eIF2B is a substrate for glycogen synthase kinase (GSK)-3 in vitro, and phosphorylation by GSK3 inhibits the activity of eIF2B. The site of phosphorylation has previously been identified as Ser(535).

SIGNOR-251236

P78527

P15927

1

phosphorylation

down-regulates activity

0.579

We showed previously that UV irradiation increases phosphorylation of the p34 subunit of human replication protein A (RPA) and that this hyperphosphorylation correlated with loss of activity of the DNA replication complex. | we detected phosphorylation of the RPA complex by DNA-PK on RPA-p34 sites Ser-23, Ser-29, and Ser-11, -12, or -13

SIGNOR-248981