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
Q5S007	Q8N6T3	2	phosphorylation	down-regulates	0.579	Arfgap1 is an lrrk2 kinase substrate whose gap activity is inhibited by lrrk2. The phosphorylation of arfgap1 by lrrk2 was subjected to mass spectrometry to determine the sites of phosphorylation. There was 95.3% coverage and serines(s155, s246, s284) and threonine (t189, t216, t292) are phosphorylated by lrrk2. Mutational analysis of these serine and threonine amino acids to alanine reveals that no single amino acid is the predominant phospho-amino acid.	SIGNOR-196732
Q8N6T3	Q5S007	2	binding	up-regulates	0.579	The gtp hydrolysis activity of lrrk2 is markedly enhanced by arfgap1 supporting a role for arfgap1 as a gtpase-activating protein for lrrk2.Lrrk2 and arfgap1 interact in vitro in mammalian cells and in vivo in brain, and co-localize in the cytoplasm and at golgi membranes	SIGNOR-196264
Q96J92	P55017	1	phosphorylation	up-regulates activity	0.579	Threonine 48 was identified as the WNK4 phosphorylation site at mouse NCC\|. Thus, WNK4 stimulates NCC in three ways: (1) direct phosphorylation and in turn increasing NCC protein abundance; (2) facilitating the phosphorylation of NCC by SPAK/OSR1 indirectly, and (3) phosphorylating and activating SPAK/OSR1.\|Evidences from early studies using Xenopus oocytes and mammalian cells indicate that WNK4 inhibits NCC and PHAII-causing mutations relieve the inhibition	SIGNOR-264631
P06493	Q2NKX8	1	phosphorylation	up-regulates	0.579	Following phosphorylation of pich on the cdk1 site t1063, plk1 is recruited to pich and controls its localization. Starting in prometaphase, pich accumulates at kinetochores and inner centromeres.	SIGNOR-152133
P48729	P49841	1	binding	up-regulates activity	0.579	In the absence of secreted wnt ligands, cytosolic beta-catenin is phosphorylated at ser45 by the priming kinase casein kinase 1 (ck1). Consequently, glycogen synthase kinase 3 (gsk3), in complex with axin and adenomatous polyposis coli (apc), phosphorylates beta-catenin at thr41, ser37, and ser33 apc cooperates with axin to promote the phosphorylation of b-catenin by gsk3 [which requires priming phosphorylation by casein kinase 1, alpha-isoform (ck1alpha)]	SIGNOR-184696
P24941	Q8WXE1	1	phosphorylation	up-regulates	0.579	Atrip is a cdk2 substrate, and cdk2-dependent phosphorylation of s224 regulates the ability of atr-atrip to promote cell cycle arrest in response to dna damage./ One possibility is s224 phosphorylation creates a binding site for another protein involved in the g2-m checkpoint response	SIGNOR-156928
P20309	P50148	1	binding	up-regulates activity	0.579	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-257018
P28328	P50542	1	ubiquitination	down-regulates quantity by destabilization	0.579	Here we report on the identification of the protein-ubiquitin ligases that are responsible for the ubiquitination of the peroxisomal protein import receptor Pex5. It is demonstrated that each of the three RING peroxins Pex2, Pex10, and Pex12 exhibits ubiquitin-protein isopeptide ligase activity. Our results show that Pex2 mediates the Ubc4-dependent polyubiquitination whereas Pex12 facilitates the Pex4-dependent monoubiquitination of Pex5.While polyubiquitinated Pex5 is degraded by the proteasome, monoubiquitinated Pex5 is destined for a new round of the receptor cycle.	SIGNOR-253021
P48729	P63104	1	phosphorylation	down-regulates activity	0.579	This protein kinase has been identified as casein kinase Ialpha (CKIalpha) by peptide mapping analysis and sequencing. Among mammalian 14-3-3, only 14-3-3 tau possesses a phosphorylatable residue at the same position (Ser-233), and we show that this residue is also phosphorylated by CKI. In addition, we show that 14-3-3 zeta is exclusively phosphorylated on Thr-233 in human embryonic kidney 293 cells. The residue 233 is located within a region shown to be important for the association of 14-3-3 to target proteins. \| We have now shown that in vivo phosphorylation of 14-3-3 zeta at the CKIalpha site (Thr-233) negatively regulates its binding to c-Raf, and may be important in Raf-mediated signal transduction.	SIGNOR-250796
Q9UHD2	Q04864	1	phosphorylation	up-regulates	0.579	The present results demonstrate that ikkepsilon- and tbk1-mediated phosphorylation of crel in the c-terminal td leads to cytoplasmic dissociation of a crel-ikb_ complex and nuclear accumulation of crel.	SIGNOR-148623
Q15797	O43541	2	transcriptional regulation	up-regulates quantity	0.579	Chromatin immunoprecipitation (ChIP) revealed a subset of the BIG (BMP4 induced genes) signature, including Satb2, Smad6, Hand1, Gadd45γ and Gata3, that was bound by Smad1/5 in the developing mandible, revealing direct Smad-mediated regulation	SIGNOR-268935
P55285	P35222	1	binding	up-regulates activity	0.578	At its C-terminus, cadherin interacts with Î²-catenin, which dynamically associates with Î±-catenin, a direct binding partner of filamentous actin	SIGNOR-265868
P06239	Q9NP31	1	phosphorylation	up-regulates activity	0.578	Here we mapped Lck phosphorylation and interaction sites on TSAd and evaluated their functional importance. The three C-terminal TSAd tyrosines Tyr(280), Tyr(290), and Tyr(305) were phosphorylated by Lck and functioned as docking sites for the Lck Src homology 2 (SH2) domain. Lck binds to TSAd prolines and phosphorylates and interacts with the three C-terminal TSAd tyrosines. We propose that through multivalent interactions with Lck, TSAd diverts Lck from phosphorylating other substrates, thus modulating its functional activity through substrate competition.	SIGNOR-262888
P48730	P04637	1	phosphorylation	up-regulates	0.578	Here we show that the direct association between a p53 n-terminal peptide and mdm2 is disrupted by phosphorylation of the peptide on thr(18) but not by phosphorylation at other n-terminal sites, including ser(15) and ser(37). Thr(18) was phosphorylated in vitro by casein kinase (ck1).	SIGNOR-75889
P04049	P06400	1	phosphorylation	down-regulates activity	0.578	Further, Raf-1 was able to phosphorylate Rb in vitro quite efficiently.\|Raf-1 can inactivate Rb function and can reverse Rb mediated repression of E2F1 transcription and cell proliferation efficiently.	SIGNOR-279481
Q6SA08	P16220	1	phosphorylation	up-regulates	0.578	Tssk5, a novel member of the testis-specific serine/threonine kinase family, phosphorylates creb at ser-133, and stimulates the cre/creb responsive pathway.	SIGNOR-138289
O95155	P54252	1	polyubiquitination	down-regulates quantity by destabilization	0.578	Mammalian E4B (UFD2a), a ubiquitin chain assembly factor (E4), copurified with the polyubiquitylation activity for ataxin-3. E4B interacted with, and thereby mediated polyubiquitylation of, ataxin-3. Collectively, these data suggest that E4B promotes the degradation of ataxin-3, and that this effect surmounts the stabilization of ataxin-3 conferred by expansion of the polyglutamine tract.	SIGNOR-271502
Q92831	Q15796	1	acetylation	up-regulates	0.578	We demonstrate that both smad2 and smad3 are acetylated by the coactivators p300 and cbp in a tgfbeta-dependent manner. Smad2 is also acetylated by p/caf. The acetylation of smad2 was significantly higher than that of smad3. Lys(19) in the mh1 domain was identified as the major acetylated residue in both the long and short isoform of smad2.....acetylation of the short isoform of smad2 improves its dna binding activity in vitro and enhances its association with target promoters in vivo, thereby augmenting its transcriptional activity	SIGNOR-150273
Q96J02	P08151	1	ubiquitination	down-regulates	0.578	The consequent activation of_ itch, together with the recruitment of gli1 through direct binding with_ numb, allows gli1 to enter into the complex, resulting in gli1 ubiquitination and degradation. we demonstrate that the hedgehog transcription factor gli1 is targeted by numb for itch-dependent ubiquitination, which suppresses hedgehog signals, thus arresting growth and promoting cell differentiation	SIGNOR-150847
Q9P212	P01112	1	guanine nucleotide exchange factor	up-regulates	0.578	The presence of a rasgef motif in the n terminus of plcepsilon suggests that plcepsilon can activate ras by acting as an exchange factor by promoting the exchange of gtp for bound gdp.	SIGNOR-82859
P28482	Q07869	1	phosphorylation	up-regulates activity	0.578	We now demonstrate that amino acids 1-92 of hPPARalpha contain an activation function (AF)-1-like domain, which is further activated by insulin through a pathway involving the mitogen-activated protein kinases p42 and p44. Further analysis of the amino-terminal region of PPARalpha revealed that the insulin-induced trans-activation occurs through the phosphorylation of two mitogen-activated protein kinase sites at positions 12 and 21, both of which are conserved across evolution.	SIGNOR-249434
P29459	Q99665	1	binding	up-regulates	0.578	Il-12r beta 2 plays an essential role in mediating the biological functions of il-12 in mice.	SIGNOR-84361
P12931	P51692	1	phosphorylation	up-regulates	0.578	Stat5 is activated by a broad spectrum of cytokines, as well as non-receptor tyrosine kinases, such as src. these conformational differences may in part be due to differential effects of prl and src on stat5b tyrosine phosphorylation, since src induced several additional sites of tyrosine phosphorylation of stat5b at residues other than tyr-699, including tyr-724 and tyr-679.	SIGNOR-99002
O15264	O00418	1	phosphorylation	down-regulates activity	0.578	eEF2 kinase is phosphorylated and inhibited by SAPK4/p38delta. eEF2K[S359A] was phosphorylated (presumably at Ser396) by the high concentrations of SAPK4/p38 used in this experiment. However, the inhibition of eEF2K under these conditions was reduced from 82% in the wild-type enzyme to 19% in eEF2K[S359A]	SIGNOR-250089
Q7L7X3	P46734	1	phosphorylation	up-regulates activity	0.578	The activation of and binding to MEK3 by TAO1 implicates TAO1 in the regulation of the p38-containing stress-responsive MAP kinase pathway	SIGNOR-60818
Q70E73	P50552	1	binding	up-regulates activity	0.578	Here we show that Lpd is a substrate of Abl kinases and binds to the Abl SH2 domain. Phosphorylation of Lpd positively regulates the interaction between Lpd and Ena/VASP proteins.	SIGNOR-268426
P06493	Q9H8V3	1	phosphorylation	down-regulates	0.577	We show that phosphorylation of ect2 at threonine-341 (t341) affects the autoregulatory mechanism of ect2. In g2/m phase, ect2 was phosphorylated at t341 most likely by cyclin b/cyclin-dependent kinase 1 (cdk1) ect2 is biologically active even when it is not phosphorylated at t341	SIGNOR-140549
P10586	P06213	1	dephosphorylation	down-regulates	0.577	Lar ptpase shows strong preference for dephosphorylation first at py5 (at tri-, di-, and monophosphotyrosyl levels). Initially this regioselectivity gives the y5(py9)(py10) diphospho regioisomer, followed by equal dephosphorylation at py9 or py10 to give the corresponding monophosphoryl species on the way to fully dephosphorylated product.	SIGNOR-76005
Q9UEW8	Q13621	1	phosphorylation	up-regulates activity	0.577	We establish that the SPAK and OSR1 kinases activated by WNK interact with an RFQV motif on NKCC2 and directly phosphorylate Thr95, Thr100, Thr105 and, possibly, Ser91.Using these phosphorylation-specific antibodies we establish that hypotonic low-chloride stimulation induces marked phosphorylation of overexpressed NKCC2 in HEK-293 cells at Ser91, Thr100, Thr105 and Ser130 (Fig. 3A).	SIGNOR-276308
Q9Y490	P18564	1	binding	up-regulates activity	0.577	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-257631
P11441	O43765	1	binding	up-regulates activity	0.577	USP13 and gp78 control ubiquitination of Ubl4A.These data suggest that USP13 and gp78 play antagonizing roles in regulation of Ubl4A ubiquitination: While gp78 assembles ubiquitin chains on Ubl4A, USP13 antagonizes this activity to limit Ubl4A ubiquitination.Ubiquitination of Ubl4A preferentially occurs on Lys48. We identify the Bag6 cofactor Ubl4A as a shared substrate of gp78 and USP13. USP13 depletion is associated with hyper-ubiquitination of Ubl4A and altered interaction between the Bag6 complex and its co-chaperone SGTA. Because the interaction of Ubl4A with SGTA is mediated by positively-charged residues in Ubl4A including Lys48 (Chartron et al., 2012; Xu et al., 2012), which happens to be the major ubiquitination site, the simplest model to explain reduced Bag6-SGTA interaction in USP13 knockdown cells is that ubiquitin conjugates on Ubl4A sterically hinder SGTA binding.	SIGNOR-272858
P00533	P15941	1	phosphorylation	up-regulates activity	0.577	We also show that the activated egf-r phosphorylates the muc1 cytoplasmic tail on tyrosine at a yekv motif that functions as a binding site for the c-src sh2 domain. The results demonstrate that egf-r-mediated phosphorylation of muc1 induces binding of muc1 to c-src in cells	SIGNOR-109538
P27361	P16949	1	phosphorylation	down-regulates activity	0.577	Stress-induced stathmin phosphorylation is not de- pendent on ERK. Stathmin is also known to be phos- phorylated by ERK on Ser-25 and Ser-38 (17). Thus, it is possible that ERK phosphorylates stathmin in 293 cells\|In subsequent reports (28, 29) it was shown that phosphorylation of stathmin blocks its ability to destabilize MTs.	SIGNOR-249483
P24530	P50148	1	binding	up-regulates activity	0.577	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-257379
Q9H173	P11021	1	binding	up-regulates activity	0.577	BAP, a Mammalian BiP-associated Protein, Is a Nucleotide Exchange Factor That Regulates the ATPase Activity of BiP. In addition,BAP was associated with BiP in mammalian cells and inter-acted with BiP functionallyin vitro. BAP stimulated the ATPase activity of BiP when added alone or together with the ER DnaJ protein, ERdj4, by promoting the release of ADP from BiP. Together, these data demonstrate that BAP serves as a nucleotide exchange factor for BiP and provide insights into the mechanisms that control protein folding in the mammalian ER.	SIGNOR-261045
Q9C0H5	P60953	1	gtpase-activating protein	down-regulates activity	0.577	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-260495
Q2M1P5	P10071	1	binding	up-regulates quantity by stabilization	0.577	These results suggest a role for Kif7 in coordinating Hh signal transduction at the tip of cilia and preventing Gli3 cleavage into a repressor form in the presence of Hh.	SIGNOR-209614
Q9UBU6	Q86TM6	1	binding	up-regulates activity	0.577	FAM8A1 enhances binding of Herp to Hrd1, an interaction that is required for ERAD. Our findings support a model of Hrd1 complex formation, where the Hrd1 cytoplasmic domain and FAM8A1 have a central role in the assembly and activity of this ERAD machinery. A conserved Hrd1 cytoplasmic domain interacts with FAM8A1 and Herp	SIGNOR-261348
O15530	Q05513	1	phosphorylation	up-regulates	0.577	Our findings suggest that insulin, via pip(3), provokes increases in pkc-zeta enzyme activity through (a) pdk-1-dependent t410 loop phosphorylation, (b) t560 autophosphorylationcytoskeletal reorganization;tnni1(induces);desmin(induces);tpm1(induces);myo1c(induces);tnnt1(induces);	SIGNOR-85501
P54646	P49815	1	phosphorylation	up-regulates	0.577	We have observed that ampk directly phosphorylates tsc2, and the ampk-dependent phosphorylation of tsc2 is critical for the coordination between cell growth and cellular energy levels.	SIGNOR-149388
O15530	Q05655	1	phosphorylation	up-regulates activity	0.577	PDK1 phosphorylated the activation loop sites of PKCzeta and PKCdelta in vitro and in a phosphoinositide 3-kinase (PI 3-kinase)-dependent manner in vivo in human embryonic kidney (293) cells. PKCδ was also phosphorylated in the activation loop site (T505)	SIGNOR-250269
P23769	P17947	1	binding	down-regulates activity	0.577	Here we demonstrate that a region of the PU.1 Ets domain (the winged helix–turn–helix wing) interacts with the conserved carboxyl-terminal zinc finger of GATA-1 and GATA-2 and that GATA proteins inhibit PU.1 transactivation of critical myeloid target genes.	SIGNOR-256071
Q9BUB5	P47712	1	phosphorylation	up-regulates activity	0.577	The results suggest that MNK1 or a closely related kinase is responsible for in vivo phosphorylation of cPLA2 on Ser-727.	SIGNOR-226633
Q05513	Q13164	1	phosphorylation	down-regulates activity	0.577	Furthermore, PKC\u03b6 phosphorylates ERK5, and mutation analysis showed that the preferred site is S486.\|PKCzeta decreases eNOS protein stability via inhibitory phosphorylation of ERK5	SIGNOR-280090
P12931	Q92529-2	1	phosphorylation	up-regulates activity	0.576	We also obtained tryptic phosphopeptide maps of N-Shc protein phosphorylated in vitro by other tyrosine kinases, TrkB, v-Src and EGFR. The overall patterns of the phosphopeptide maps generated by these tyrosine kinases were similar, although there were some differences among these maps (Figure 4a–d).We performed phosphopeptide mapping analysis using GST-fused N-Shc protein, and found that N-Shc phosphorylated by TrkA in vitro was resolved into at least seven phosphopeptides (Y1 through Y7, Figure 4a). Phosphopeptide mapping revealed that N-Shc has novel tyrosine-phosphorylation sites at Y259/Y260 and Y286; in vivo-phosphorylation of these tyrosines was demonstrated by site-specific anti-pTyr antibodies. Phosphorylated Y286 bound to several proteins, of which one was Crk. The pY221/pY222 site, corresponding to one of the Grb2-binding sites of Shc, also preferentially bound to Crk. The phosphorylation-dependent interaction between N-Shc and Crk was demonstrated in vitro and in vivo.	SIGNOR-273921
Q13634	P35222	1	binding	up-regulates activity	0.576	At its C-terminus, cadherin interacts with Î²-catenin, which dynamically associates with Î±-catenin, a direct binding partner of filamentous actin	SIGNOR-265857
P29323	P20936	1	binding	up-regulates	0.576	We have localized an in vitro rasgap-binding site to conserved tyrosine residues y604 and y610 in the juxtamembrane region of ephb2, and demonstrated that substitution of these amino acids abolishes ephrin-b1-induced signalling events in ephb2-expressing ng108-15 cells.	SIGNOR-50100
P29350	P15498	1	dephosphorylation	down-regulates activity	0.576	SHP-1 dephosphorylates and inactivates the guanine exchange factor Vav1.	SIGNOR-277171
P00533	P16333	1	binding	up-regulates activity	0.576	We show that epidermal growth factor or platelet-derived growth factor stimulation of intact human or murine cells leads to phosphorylation of Nck protein on tyrosine, serine, and threonine residues	SIGNOR-252089
P0DP25	P16298	1	binding	up-regulates	0.576	Calcium-bound calmodulin associates with calcineurin (cn), releasing the phosphatase from the repressive effects on an autoinhibitory domain.	SIGNOR-266338
Q6PIJ6	O75840	1	binding	up-regulates activity	0.576	Interaction between MoKA and KLF7 was confirmed by the in vitro glutathione S-transferase pull-down assay and by coimmunoprecipitation of the proteins overexpressed in mammalian cells. Functional assays documented that MoKA is a KLF7 coactivator	SIGNOR-224621
P50148	P61586	1	binding	up-regulates	0.576	Recently, the dbl-family guanine nucleotide exchange factor (gef) p63rhogef/geft has been described as a novel mediator of galpha(q/11) signaling to rhoa based on its ability to synergize with galpha(q/11) resulting in enhanced rhoa signaling in cells.	SIGNOR-156534
P27361	Q9BUB5	1	phosphorylation	up-regulates	0.576	Mnk1 was phosphorylated and activated in vitro by erk1 and p38 map kinasespreliminary results showed that thr344 at least was one of the major sites phosphorylated by erk1	SIGNOR-48360
O14965	P14635	1	phosphorylation	up-regulates activity	0.576	A second wave of Cyclin B1-CDK1 phosphorylation by AurA occurs in late prophase.\|Simultaneously, AurA activates and targets the Cyclin B1-CDK1 complex at centrosomes [ xref ].	SIGNOR-280186
P07949	Q8TEW6	1	binding	up-regulates	0.576	We identified two new family members, dok-4 and dok-5, that can directly associate with y1062 of c-ret dok-4 and dok-5 enhance c-ret-dependent activation of mitogen-activated protein kinase	SIGNOR-109513
P29350	P10721	1	binding	down-regulates	0.576	Shp-1 binds and negatively modulates the c-kit receptor by interaction with tyrosine 569 in the c-kit juxtamembrane domain.	SIGNOR-56104
P60484	P35568	1	dephosphorylation	down-regulates activity	0.576	In contrast, IRS-1 level were significantly decreased and phosphorylation of IRS-1 at Ser 307 was strongly enhanced by PTEN knockdown, suggesting that both reduction in IRS-1 level and increase in IRS-1 phosphorylation at Ser307 upon HCV infection occurred in a PTEN dependent manner.\|In contrast, IRS-1 level were significantly decreased and phosphorylation of IRS-1 at Ser-307 was strongly enhanced by PTEN knockdown, suggesting that both reduction in IRS-1 level and increase in IRS-1 phosphorylation at Ser307 upon Hepatitis C virus infection occurred in a PTEN-dependent manner.	SIGNOR-277078
P22681	Q8WU20	1	ubiquitination	down-regulates	0.576	The experiments presented in this report illustrate that in response to fgf stimulation, cbl is recruited by grb2 binding to the frs2_ multiprotein complex, resulting in ubiquitination of frs2_ and fgfr. grb2 functions as a link between frs2_ and cbl;grb2 is bound to tyrosine-phosphorylated frs2_ by means of its sh2 domain and to a proline-rich region in the c terminus of cbl by means of its sh3 domains.	SIGNOR-87166
P54727	P27694	1	binding	up-regulates activity	0.575	GG-NER is initiated by the GG-NER specific factor XPC-RAD23B, in some cases with the help of UV-DDB (UV-damaged DNA-binding protein). TC-NER is initiated by RNA polymerase stalled at a lesion with the help of TC-NER specific factors CSA, CSB, and XAB2. Both pathways require the core NER factors to complete the excision process\|The core NER dual incision reaction has been reconstituted in vitro with purified factors using XPC-RAD23B, TFIIH, XPA, RPA, XPG, and ERCC1-XPF (Aboussekhra et al. 1995; Mu et al. 1995; Araujo et al. 2000).\|The core NER dual incision reaction has been reconstituted in vitro with purified factors using XPC-RAD23B, TFIIH, XPA, RPA, XPG, and ERCC1-XPF (Aboussekhra et al. 1995; Mu et al. 1995; Araujo et al. 2000). Functional studies revealed that XPC-RAD23B is the initial damage recognition factor in this system, as the presence of XPC-RAD23B is required for assembly of the other core NER factors and progression through the NER pathway both in vitro and in vivo	SIGNOR-275698
P06241	P16885	1	phosphorylation	up-regulates activity	0.575	The phosphorylation of purified phospholipase C-gamma 1 (PLC-gamma 1) and PLC-gamma 2 by src-family-protein tyrosine kinases (PTKs) P56lck, p53/56lyn, p59hck, p59fyn, and p60src was studied in vitro. All five PTKs phosphorylated PLC-gamma 1 and PLC-gamma 2, suggesting that both PLC-gamma isozymes can be phosphorylated in cells by any of the src-family PTKs in response to the activation of cell surface receptors.	SIGNOR-249340
Q13131	Q9UBK2	1	phosphorylation	up-regulates activity	0.575	Ampk phosphorylates pgc-1alpha directly both in vitro and in cells. These direct phosphorylations of the pgc-1alpha protein at threonine-177 and serine-538.	SIGNOR-156780
P18031	Q13882	1	dephosphorylation	down-regulates activity	0.575	Using a variety of PTEN mutant constructs, we show that protein phosphatase activity of PTEN targets PTK6, with efficiency similar to PTP1B, a phosphatase that directly dephosphorylates PTK6 Y342.	SIGNOR-277082
P10275	O15393	1	transcriptional regulation	up-regulates quantity by expression	0.575	The prostate-specific TMPRSS2 gene, while upregulated by AR activity in luminal cells, is also transcribed in basal populations, confirming that AR acts as an expression modulator.	SIGNOR-253687
P24941	O15350	1	phosphorylation	down-regulates activity	0.575	Cyclin-dependent kinases phosphorylate p73 at threonine 86 in a cell cycle-dependent manner and negatively regulate p73.Furthermore, cyclin a/cdk1/2, cyclin b/cdk1/2, and cyclin e/cdk2 complexes can phosphorylate multiple p73 isoforms in vitro at threonine 86.	SIGNOR-99746
P27348	P30307	1	relocalization	down-regulates	0.575	Cdc25c: nuclear exclusion/cytoplasmic sequestration via binding to 14-3-3 proteins.	SIGNOR-163237
Q01453	P25189	1	binding	up-regulates activity	0.575	Our data provide the first direct evidence for the formation of P0–PMP22 complexes at the plasma membrane. These protein interactions probably participate in holding adjacent Schwann cell membranes together and in stabilizing myelin compaction.	SIGNOR-251898
P35222	Q01860	1	binding	up-regulates activity	0.575	We provide evidence suggesting that Beta-catenins interaction with the pluripotency regulator Oct-4 at least partially underlies its effects on sustaining pluripotency.	SIGNOR-241981
Q9ULV1	Q92997	1	binding	up-regulates activity	0.575	Through study of FZD4 and its associated ligand Norrin, we report that a minimum of three residues distal to the KTXXXW motif in the C-terminal tail of Frizzled-4 are essential for DVL recruitment and robust Lef/Tcf-dependent transcriptional activation in response to Norrin.	SIGNOR-258961
Q8NBL1	Q04721	1	binding	up-regulates	0.575	O-glucosylation of epidermal growth factor-like (egf) repeats in the extracellular domain of notch is essential for notch function. O-glucose can be elongated by xylose to the trisaccharide, xylalfa1-3xylalfa1-3glcbeta1-o-ser, whose synthesis is catalyzed by the consecutive action of three glycosyltransferases. A udp-glucose:protein o-glucosyltransferase (poglut/rumi) transfers o-glucose to serine within the o-glucose consensus.	SIGNOR-198716
P06493	Q15910	1	phosphorylation	down-regulates	0.575	Cdk1, which phosphorylates ezh2 at threonines 345 and 487.Phosphorylation of thr-345 and thr-487 promotes ezh2 ubiquitination and subsequent degradation by the proteasome	SIGNOR-174058
P06493	P62136	1	phosphorylation	down-regulates activity	0.575	Both of these pp1 isoforms contain an arg-pro-ile/val-thr-pro-pro-arg sequence near the c terminus, a known site of phosphorylation by cdc/cdk kinases, and phosphorylation attenuates phosphatase activity.	SIGNOR-151799
P46937	Q15797	1	binding	up-regulates	0.575	Yap binds to the phosphorylated smad1 to activate gene transcription.	SIGNOR-201462
P29590	O95405	1	binding	up-regulates	0.574	Cytoplasmic pml physically interacts with smad2/3 and sara (smad anchor for receptor activation) and is required for association of smad2/3 with sara and for the accumulation of sara and tgf-beta receptor in the early endosome.	SIGNOR-128744
Q14344	P61586	1	binding	up-regulates	0.574	Ga12/13 recruitment of rho-gefs causes rhoa activation and f-actin assembly, which promotes lats1/lat2 inactivation by an unknown, but myosin-independent mechanism.	SIGNOR-192111
O14757	O75461	1	phosphorylation	down-regulates activity	0.574	the checkpoint kinase Chk1 phosphorylates E2F6 leading to its dissociation from promoters.	SIGNOR-266371
P00750	P00747	2	binding	up-regulates activity	0.574	The conversion of plasminogen to plasmin can occur by several different mechanisms, but it appears that the most important in uiuo activator is tPA (2). tPA, M, = 70,000, is present in plasma as a single-chain serine protease, but proteolytic cleavage of the Agr275-Ile276 bond in tPA by plasmin yields a disulfide-linked two-chain enzyme	SIGNOR-263533
Q05397	P63000	1	phosphorylation	up-regulates activity	0.574	Both Src and FAK phosphorylate Rac1 at tyrosine 64.\|Our investigations of direct interactions between Rac1, Src, and FAK were motivated by our previous insights into FAK augmentation of Rac1 activation during cell spreading, and the Cerione lab 's work on the interactions between Src and Cdc42 , .	SIGNOR-279652
Q13217	Q9P2K8	1	binding	down-regulates activity	0.574	we show that p58IPK is a general inhibitor of the eIF2 kinases in that it also interacts with GCN2	SIGNOR-246204
P06241	P43403	1	phosphorylation	up-regulates activity	0.574	Subsequently, Lck and Fyn phosphorylate and activate the Syk family kinase ZAP-70 when it is recruited to the phosphorylated ITAM motifs xref .	SIGNOR-279043
Q05397	P12814	2	phosphorylation	down-regulates activity	0.574	The cytoskeletal/non-muscle isoform of alpha-actinin is phosphorylated on its actin-binding domain by the focal adhesion kinase tyrosine 12 is the site of phosphorylation. The wild type recombinant protein was not phosphorylated in cells lacking the focal adhesion kinase (fak).Tyrosine phosphorylation reduced the amount of alpha-actinin that cosedimented with actin filaments.	SIGNOR-108329
Q13546	Q8N5C8	1	binding	up-regulates activity	0.574	Tab2 and tab3 activate the jun n-terminal kinase and nuclear factor-kappab pathways through the specific recognition of lys 63-linked polyubiquitin chains by its npl4 zinc-finger (nzf) domain.	SIGNOR-161787
P41279	Q02750	1	phosphorylation	up-regulates	0.574	Activation of mek family kinases requires phosphorylation of two conserved ser/thr residues.Phosphopeptide analysis demonstrated that serine residues 218 and 222 of human mek1 are the primary sites for phosphorylation by c-raf	SIGNOR-36453
P21731	Q14344	1	binding	up-regulates activity	0.574	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-257139
Q92918	Q16584	1	phosphorylation	up-regulates	0.574	Hpk1 also phosphorylated mlk-3 activation loop in vitro, and ser281 was found to be the major phosphorylation site, indicating that hpk1 also activates mlk-3 via phosphorylation of the kinase activation loop.	SIGNOR-83415
Q00535	P37231	1	phosphorylation	down-regulates activity	0.574	CDK5 in turn phosphorylates PPARgamma at Ser273 and prevents the transcription of specific PPARgamma target genes that have anti-diabetic effects .	SIGNOR-278189
O43541	Q13485	1	binding	down-regulates activity	0.574	On the other hand, Smad6 competes with R-Smad and forms a non-functional complex with Smad4, which will inhibit BMP signaling in bone formation. Smad6 is involved in a negative feedback loop regulating BMP signaling and is required to limit BMP signaling during endochondral bone formation.	SIGNOR-195648
P00747	P00750	2	cleavage	up-regulates activity	0.574	The conversion of plasminogen to plasmin can occur by several different mechanisms, but it appears that the most important in uiuo activator is tPA (2). tPA, M, = 70,000, is present in plasma as a single-chain serine protease, but proteolytic cleavage of the Agr275-Ile276 bond in tPA by plasmin yields a disulfide-linked two-chain enzyme	SIGNOR-263534
Q86TM6	Q15011	1	binding	up-regulates activity	0.574	FAM8A1 enhances binding of Herp to Hrd1, an interaction that is required for ERAD. Our findings support a model of Hrd1 complex formation, where the Hrd1 cytoplasmic domain and FAM8A1 have a central role in the assembly and activity of this ERAD machinery. A conserved Hrd1 cytoplasmic domain interacts with FAM8A1 and Herp	SIGNOR-261349
P12814	Q05397	2	binding	down-regulates activity	0.574	Consistent with the results obtained with COS-7 cells, coexpression of wild-type Œ±-actinin with PTP 1B in PTP 1B-null cells resulted in Src/Œ±-actinin binding and limited the interaction between FAK and Src	SIGNOR-261799
Q92831	Q06413	1	binding	up-regulates	0.573	The cofactors grip-1, cbp/p300 and pcaf have hat activity and function as co-activators for mef-2c during myogenesis.	SIGNOR-84032
O00444	Q15154	1	phosphorylation	up-regulates activity	0.573	Plk4‚Äêmediated phosphorylation of PCM1 at S372 is critical for the proper localisation of centriolar satellites, its dimer formation and interaction with other satellite components\|Therefore, Plk4 is responsible for PCM1 phosphorylation at S372.	SIGNOR-279556
O15530	Q02156	1	phosphorylation	up-regulates	0.573	In the present study, we analysed the contribution of the phosphoinositide-dependent kinase 1 (pdk-1) and pkcepsilon kinase activity in controlling the phosphorylation of thr(566) and ser(729). pdk-1 phosphorylation of the activation loop triggers autophosphorylation of the hydrophobic motif	SIGNOR-117320
Q15831	Q96EB6	1	phosphorylation	up-regulates activity	0.573	Resveratrol promotes the binding between LKB1 and Sirt1, which we first reported, and this binding leads to LKB1-mediated phosphorylation of Sirt1 at three different serine residues in the C terminus of Sirt1. Mechanistically, LKB1-mediated phosphorylation increases intramolecular interactions in Sirt1, such as the binding of the C terminus to the deacetylase core domain, thereby eliminating DBC1 (Deleted in Breast Cancer 1, Sirt1 endogenous inhibitor) inhibition and promoting Sirt1-substrate interaction.	SIGNOR-277323
Q02156	Q86XR7	1	phosphorylation	up-regulates	0.573	Here we show that tram is transiently phosphorylated by pkcepsilon on serine-16 our study provides a possible target for these molecules in lps signaling. Dag may activate pkc?, Leading to the phosphorylation and activation of tram.	SIGNOR-146991
O14842	P50148	1	binding	up-regulates activity	0.573	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-257272
P20749	Q00653	1	binding	up-regulates	0.573	The cyclin d1 elevation is caused not by increased p65/p50 action but rather by increased nuclear activity of bcl-3-associated nf-kappab p50 and p52.	SIGNOR-146768
Q13526	P01106	1	binding	up-regulates	0.573	Pin1 prolyl isomerase enhances recruitment of serine 62-phosphorylated myc and its coactivators to select promoters during gene activation.	SIGNOR-202134
Q14814	P23409	1	transcriptional regulation	up-regulates quantity by expression	0.573	Myogenin and MEF2 function synergistically to activate the MRF4 promoter during myogenesis.	SIGNOR-238715
P35348	P29992	1	binding	up-regulates activity	0.573	In this report, we demonstrate that in transfected cos-7 cells Gal4 and Ga16, like Gaq and Ga11, can activate PIPLC j3l and that all three al-ARs, alA, alB and alC, can activate endogenous PI-PLC by coupling to Gaq or Ga11.	SIGNOR-278121
Q9BW19	Q02224	1	binding	up-regulates activity	0.573	We found that KIFC1 could directly bind to CENPE in SKOV3 cells (Figure 4C, 4D).	SIGNOR-266116

Q5S007

Q8N6T3

2

phosphorylation

down-regulates

0.579

Arfgap1 is an lrrk2 kinase substrate whose gap activity is inhibited by lrrk2. The phosphorylation of arfgap1 by lrrk2 was subjected to mass spectrometry to determine the sites of phosphorylation. There was 95.3% coverage and serines(s155, s246, s284) and threonine (t189, t216, t292) are phosphorylated by lrrk2. Mutational analysis of these serine and threonine amino acids to alanine reveals that no single amino acid is the predominant phospho-amino acid.

SIGNOR-196732

Q8N6T3

Q5S007

2

binding

up-regulates

0.579

The gtp hydrolysis activity of lrrk2 is markedly enhanced by arfgap1 supporting a role for arfgap1 as a gtpase-activating protein for lrrk2.Lrrk2 and arfgap1 interact in vitro in mammalian cells and in vivo in brain, and co-localize in the cytoplasm and at golgi membranes

SIGNOR-196264

Q96J92

P55017

1

phosphorylation

up-regulates activity

0.579

Threonine 48 was identified as the WNK4 phosphorylation site at mouse NCC|. Thus, WNK4 stimulates NCC in three ways: (1) direct phosphorylation and in turn increasing NCC protein abundance; (2) facilitating the phosphorylation of NCC by SPAK/OSR1 indirectly, and (3) phosphorylating and activating SPAK/OSR1.|Evidences from early studies using Xenopus oocytes and mammalian cells indicate that WNK4 inhibits NCC and PHAII-causing mutations relieve the inhibition

SIGNOR-264631

P06493

Q2NKX8

1

phosphorylation

up-regulates

0.579

Following phosphorylation of pich on the cdk1 site t1063, plk1 is recruited to pich and controls its localization. Starting in prometaphase, pich accumulates at kinetochores and inner centromeres.

SIGNOR-152133

P48729

P49841

1

binding

up-regulates activity

0.579

In the absence of secreted wnt ligands, cytosolic beta-catenin is phosphorylated at ser45 by the priming kinase casein kinase 1 (ck1). Consequently, glycogen synthase kinase 3 (gsk3), in complex with axin and adenomatous polyposis coli (apc), phosphorylates beta-catenin at thr41, ser37, and ser33 apc cooperates with axin to promote the phosphorylation of b-catenin by gsk3 [which requires priming phosphorylation by casein kinase 1, alpha-isoform (ck1alpha)]

SIGNOR-184696

P24941

Q8WXE1

1

phosphorylation

up-regulates

0.579

Atrip is a cdk2 substrate, and cdk2-dependent phosphorylation of s224 regulates the ability of atr-atrip to promote cell cycle arrest in response to dna damage./ One possibility is s224 phosphorylation creates a binding site for another protein involved in the g2-m checkpoint response

SIGNOR-156928

P20309

P50148

1

binding

up-regulates activity

0.579

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-257018

P28328

P50542

1

ubiquitination

down-regulates quantity by destabilization

0.579

Here we report on the identification of the protein-ubiquitin ligases that are responsible for the ubiquitination of the peroxisomal protein import receptor Pex5. It is demonstrated that each of the three RING peroxins Pex2, Pex10, and Pex12 exhibits ubiquitin-protein isopeptide ligase activity. Our results show that Pex2 mediates the Ubc4-dependent polyubiquitination whereas Pex12 facilitates the Pex4-dependent monoubiquitination of Pex5.While polyubiquitinated Pex5 is degraded by the proteasome, monoubiquitinated Pex5 is destined for a new round of the receptor cycle.

SIGNOR-253021

P48729

P63104

1

phosphorylation

down-regulates activity

0.579

This protein kinase has been identified as casein kinase Ialpha (CKIalpha) by peptide mapping analysis and sequencing. Among mammalian 14-3-3, only 14-3-3 tau possesses a phosphorylatable residue at the same position (Ser-233), and we show that this residue is also phosphorylated by CKI. In addition, we show that 14-3-3 zeta is exclusively phosphorylated on Thr-233 in human embryonic kidney 293 cells. The residue 233 is located within a region shown to be important for the association of 14-3-3 to target proteins. | We have now shown that in vivo phosphorylation of 14-3-3 zeta at the CKIalpha site (Thr-233) negatively regulates its binding to c-Raf, and may be important in Raf-mediated signal transduction.

SIGNOR-250796

Q9UHD2

Q04864

1

phosphorylation

up-regulates

0.579

The present results demonstrate that ikkepsilon- and tbk1-mediated phosphorylation of crel in the c-terminal td leads to cytoplasmic dissociation of a crel-ikb_ complex and nuclear accumulation of crel.

SIGNOR-148623

Q15797

O43541

2

transcriptional regulation

up-regulates quantity

0.579

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

SIGNOR-268935

P55285

P35222

1

binding

up-regulates activity

0.578

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

SIGNOR-265868

P06239

Q9NP31

1

phosphorylation

up-regulates activity

0.578

Here we mapped Lck phosphorylation and interaction sites on TSAd and evaluated their functional importance. The three C-terminal TSAd tyrosines Tyr(280), Tyr(290), and Tyr(305) were phosphorylated by Lck and functioned as docking sites for the Lck Src homology 2 (SH2) domain. Lck binds to TSAd prolines and phosphorylates and interacts with the three C-terminal TSAd tyrosines. We propose that through multivalent interactions with Lck, TSAd diverts Lck from phosphorylating other substrates, thus modulating its functional activity through substrate competition.

SIGNOR-262888

P48730

P04637

1

phosphorylation

up-regulates

0.578

Here we show that the direct association between a p53 n-terminal peptide and mdm2 is disrupted by phosphorylation of the peptide on thr(18) but not by phosphorylation at other n-terminal sites, including ser(15) and ser(37). Thr(18) was phosphorylated in vitro by casein kinase (ck1).

SIGNOR-75889

P04049

P06400

1

phosphorylation

down-regulates activity

0.578

Further, Raf-1 was able to phosphorylate Rb in vitro quite efficiently.|Raf-1 can inactivate Rb function and can reverse Rb mediated repression of E2F1 transcription and cell proliferation efficiently.

SIGNOR-279481

Q6SA08

P16220

1

phosphorylation

up-regulates

0.578

Tssk5, a novel member of the testis-specific serine/threonine kinase family, phosphorylates creb at ser-133, and stimulates the cre/creb responsive pathway.

SIGNOR-138289

O95155

P54252

1

polyubiquitination

down-regulates quantity by destabilization

0.578

Mammalian E4B (UFD2a), a ubiquitin chain assembly factor (E4), copurified with the polyubiquitylation activity for ataxin-3. E4B interacted with, and thereby mediated polyubiquitylation of, ataxin-3. Collectively, these data suggest that E4B promotes the degradation of ataxin-3, and that this effect surmounts the stabilization of ataxin-3 conferred by expansion of the polyglutamine tract.

SIGNOR-271502

Q92831

Q15796

1

acetylation

up-regulates

0.578

We demonstrate that both smad2 and smad3 are acetylated by the coactivators p300 and cbp in a tgfbeta-dependent manner. Smad2 is also acetylated by p/caf. The acetylation of smad2 was significantly higher than that of smad3. Lys(19) in the mh1 domain was identified as the major acetylated residue in both the long and short isoform of smad2.....acetylation of the short isoform of smad2 improves its dna binding activity in vitro and enhances its association with target promoters in vivo, thereby augmenting its transcriptional activity

SIGNOR-150273

Q96J02

P08151

1

ubiquitination

down-regulates

0.578

The consequent activation of_ itch, together with the recruitment of gli1 through direct binding with_ numb, allows gli1 to enter into the complex, resulting in gli1 ubiquitination and degradation. we demonstrate that the hedgehog transcription factor gli1 is targeted by numb for itch-dependent ubiquitination, which suppresses hedgehog signals, thus arresting growth and promoting cell differentiation

SIGNOR-150847

Q9P212

P01112

1

guanine nucleotide exchange factor

up-regulates

0.578

The presence of a rasgef motif in the n terminus of plcepsilon suggests that plcepsilon can activate ras by acting as an exchange factor by promoting the exchange of gtp for bound gdp.

SIGNOR-82859

P28482

Q07869

1

phosphorylation

up-regulates activity

0.578

We now demonstrate that amino acids 1-92 of hPPARalpha contain an activation function (AF)-1-like domain, which is further activated by insulin through a pathway involving the mitogen-activated protein kinases p42 and p44. Further analysis of the amino-terminal region of PPARalpha revealed that the insulin-induced trans-activation occurs through the phosphorylation of two mitogen-activated protein kinase sites at positions 12 and 21, both of which are conserved across evolution.

SIGNOR-249434

P29459

Q99665

1

binding

up-regulates

0.578

Il-12r beta 2 plays an essential role in mediating the biological functions of il-12 in mice.

SIGNOR-84361

P12931

P51692

1

phosphorylation

up-regulates

0.578

Stat5 is activated by a broad spectrum of cytokines, as well as non-receptor tyrosine kinases, such as src. these conformational differences may in part be due to differential effects of prl and src on stat5b tyrosine phosphorylation, since src induced several additional sites of tyrosine phosphorylation of stat5b at residues other than tyr-699, including tyr-724 and tyr-679.

SIGNOR-99002

O15264

O00418

1

phosphorylation

down-regulates activity

0.578

eEF2 kinase is phosphorylated and inhibited by SAPK4/p38delta. eEF2K[S359A] was phosphorylated (presumably at Ser396) by the high concentrations of SAPK4/p38 used in this experiment. However, the inhibition of eEF2K under these conditions was reduced from 82% in the wild-type enzyme to 19% in eEF2K[S359A]

SIGNOR-250089

Q7L7X3

P46734

1

phosphorylation

up-regulates activity

0.578

The activation of and binding to MEK3 by TAO1 implicates TAO1 in the regulation of the p38-containing stress-responsive MAP kinase pathway

SIGNOR-60818

Q70E73

P50552

1

binding

up-regulates activity

0.578

Here we show that Lpd is a substrate of Abl kinases and binds to the Abl SH2 domain. Phosphorylation of Lpd positively regulates the interaction between Lpd and Ena/VASP proteins.

SIGNOR-268426

P06493

Q9H8V3

1

phosphorylation

down-regulates

0.577

We show that phosphorylation of ect2 at threonine-341 (t341) affects the autoregulatory mechanism of ect2. In g2/m phase, ect2 was phosphorylated at t341 most likely by cyclin b/cyclin-dependent kinase 1 (cdk1) ect2 is biologically active even when it is not phosphorylated at t341

SIGNOR-140549

P10586

P06213

1

dephosphorylation

down-regulates

0.577

Lar ptpase shows strong preference for dephosphorylation first at py5 (at tri-, di-, and monophosphotyrosyl levels). Initially this regioselectivity gives the y5(py9)(py10) diphospho regioisomer, followed by equal dephosphorylation at py9 or py10 to give the corresponding monophosphoryl species on the way to fully dephosphorylated product.

SIGNOR-76005

Q9UEW8

Q13621

1

phosphorylation

up-regulates activity

0.577

We establish that the SPAK and OSR1 kinases activated by WNK interact with an RFQV motif on NKCC2 and directly phosphorylate Thr95, Thr100, Thr105 and, possibly, Ser91.Using these phosphorylation-specific antibodies we establish that hypotonic low-chloride stimulation induces marked phosphorylation of overexpressed NKCC2 in HEK-293 cells at Ser91, Thr100, Thr105 and Ser130 (Fig. 3A).

SIGNOR-276308

Q9Y490

P18564

1

binding

up-regulates activity

0.577

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-257631

P11441

O43765

1

binding

up-regulates activity

0.577

USP13 and gp78 control ubiquitination of Ubl4A.These data suggest that USP13 and gp78 play antagonizing roles in regulation of Ubl4A ubiquitination: While gp78 assembles ubiquitin chains on Ubl4A, USP13 antagonizes this activity to limit Ubl4A ubiquitination.Ubiquitination of Ubl4A preferentially occurs on Lys48. We identify the Bag6 cofactor Ubl4A as a shared substrate of gp78 and USP13. USP13 depletion is associated with hyper-ubiquitination of Ubl4A and altered interaction between the Bag6 complex and its co-chaperone SGTA. Because the interaction of Ubl4A with SGTA is mediated by positively-charged residues in Ubl4A including Lys48 (Chartron et al., 2012; Xu et al., 2012), which happens to be the major ubiquitination site, the simplest model to explain reduced Bag6-SGTA interaction in USP13 knockdown cells is that ubiquitin conjugates on Ubl4A sterically hinder SGTA binding.

SIGNOR-272858

P00533

P15941

1

phosphorylation

up-regulates activity

0.577

We also show that the activated egf-r phosphorylates the muc1 cytoplasmic tail on tyrosine at a yekv motif that functions as a binding site for the c-src sh2 domain. The results demonstrate that egf-r-mediated phosphorylation of muc1 induces binding of muc1 to c-src in cells

SIGNOR-109538

P27361

P16949

1

phosphorylation

down-regulates activity

0.577

Stress-induced stathmin phosphorylation is not de- pendent on ERK. Stathmin is also known to be phos- phorylated by ERK on Ser-25 and Ser-38 (17). Thus, it is possible that ERK phosphorylates stathmin in 293 cells|In subsequent reports (28, 29) it was shown that phosphorylation of stathmin blocks its ability to destabilize MTs.

SIGNOR-249483

P24530

P50148

1

binding

up-regulates activity

0.577

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-257379

Q9H173

P11021

1

binding

up-regulates activity

0.577

BAP, a Mammalian BiP-associated Protein, Is a Nucleotide Exchange Factor That Regulates the ATPase Activity of BiP. In addition,BAP was associated with BiP in mammalian cells and inter-acted with BiP functionallyin vitro. BAP stimulated the ATPase activity of BiP when added alone or together with the ER DnaJ protein, ERdj4, by promoting the release of ADP from BiP. Together, these data demonstrate that BAP serves as a nucleotide exchange factor for BiP and provide insights into the mechanisms that control protein folding in the mammalian ER.

SIGNOR-261045

Q9C0H5

P60953

1

gtpase-activating protein

down-regulates activity

0.577

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-260495

Q2M1P5

P10071

1

binding

up-regulates quantity by stabilization

0.577

These results suggest a role for Kif7 in coordinating Hh signal transduction at the tip of cilia and preventing Gli3 cleavage into a repressor form in the presence of Hh.

SIGNOR-209614

Q9UBU6

Q86TM6

1

binding

up-regulates activity

0.577

FAM8A1 enhances binding of Herp to Hrd1, an interaction that is required for ERAD. Our findings support a model of Hrd1 complex formation, where the Hrd1 cytoplasmic domain and FAM8A1 have a central role in the assembly and activity of this ERAD machinery. A conserved Hrd1 cytoplasmic domain interacts with FAM8A1 and Herp

SIGNOR-261348

O15530

Q05513

1

phosphorylation

up-regulates

0.577

Our findings suggest that insulin, via pip(3), provokes increases in pkc-zeta enzyme activity through (a) pdk-1-dependent t410 loop phosphorylation, (b) t560 autophosphorylationcytoskeletal reorganization;tnni1(induces);desmin(induces);tpm1(induces);myo1c(induces);tnnt1(induces);

SIGNOR-85501

P54646

P49815

1

phosphorylation

up-regulates

0.577

We have observed that ampk directly phosphorylates tsc2, and the ampk-dependent phosphorylation of tsc2 is critical for the coordination between cell growth and cellular energy levels.

SIGNOR-149388

O15530

Q05655

1

phosphorylation

up-regulates activity

0.577

PDK1 phosphorylated the activation loop sites of PKCzeta and PKCdelta in vitro and in a phosphoinositide 3-kinase (PI 3-kinase)-dependent manner in vivo in human embryonic kidney (293) cells. PKCδ was also phosphorylated in the activation loop site (T505)

SIGNOR-250269

P23769

P17947

1

binding

down-regulates activity

0.577

Here we demonstrate that a region of the PU.1 Ets domain (the winged helix–turn–helix wing) interacts with the conserved carboxyl-terminal zinc finger of GATA-1 and GATA-2 and that GATA proteins inhibit PU.1 transactivation of critical myeloid target genes.

SIGNOR-256071

Q9BUB5

P47712

1

phosphorylation

up-regulates activity

0.577

The results suggest that MNK1 or a closely related kinase is responsible for in vivo phosphorylation of cPLA2 on Ser-727.

SIGNOR-226633

Q05513

Q13164

1

phosphorylation

down-regulates activity

0.577

Furthermore, PKC\u03b6 phosphorylates ERK5, and mutation analysis showed that the preferred site is S486.|PKCzeta decreases eNOS protein stability via inhibitory phosphorylation of ERK5

SIGNOR-280090

P12931

Q92529-2

1

phosphorylation

up-regulates activity

0.576

We also obtained tryptic phosphopeptide maps of N-Shc protein phosphorylated in vitro by other tyrosine kinases, TrkB, v-Src and EGFR. The overall patterns of the phosphopeptide maps generated by these tyrosine kinases were similar, although there were some differences among these maps (Figure 4a–d).We performed phosphopeptide mapping analysis using GST-fused N-Shc protein, and found that N-Shc phosphorylated by TrkA in vitro was resolved into at least seven phosphopeptides (Y1 through Y7, Figure 4a). Phosphopeptide mapping revealed that N-Shc has novel tyrosine-phosphorylation sites at Y259/Y260 and Y286; in vivo-phosphorylation of these tyrosines was demonstrated by site-specific anti-pTyr antibodies. Phosphorylated Y286 bound to several proteins, of which one was Crk. The pY221/pY222 site, corresponding to one of the Grb2-binding sites of Shc, also preferentially bound to Crk. The phosphorylation-dependent interaction between N-Shc and Crk was demonstrated in vitro and in vivo.

SIGNOR-273921

Q13634

P35222

1

binding

up-regulates activity

0.576

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

SIGNOR-265857

P29323

P20936

1

binding

up-regulates

0.576

We have localized an in vitro rasgap-binding site to conserved tyrosine residues y604 and y610 in the juxtamembrane region of ephb2, and demonstrated that substitution of these amino acids abolishes ephrin-b1-induced signalling events in ephb2-expressing ng108-15 cells.

SIGNOR-50100

P29350

P15498

1

dephosphorylation

down-regulates activity

0.576

SHP-1 dephosphorylates and inactivates the guanine exchange factor Vav1.

SIGNOR-277171

P00533

P16333

1

binding

up-regulates activity

0.576

We show that epidermal growth factor or platelet-derived growth factor stimulation of intact human or murine cells leads to phosphorylation of Nck protein on tyrosine, serine, and threonine residues

SIGNOR-252089

P0DP25

P16298

1

binding

up-regulates

0.576

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

SIGNOR-266338

Q6PIJ6

O75840

1

binding

up-regulates activity

0.576

Interaction between MoKA and KLF7 was confirmed by the in vitro glutathione S-transferase pull-down assay and by coimmunoprecipitation of the proteins overexpressed in mammalian cells. Functional assays documented that MoKA is a KLF7 coactivator

SIGNOR-224621

P50148

P61586

1

binding

up-regulates

0.576

Recently, the dbl-family guanine nucleotide exchange factor (gef) p63rhogef/geft has been described as a novel mediator of galpha(q/11) signaling to rhoa based on its ability to synergize with galpha(q/11) resulting in enhanced rhoa signaling in cells.

SIGNOR-156534

P27361

Q9BUB5

1

phosphorylation

up-regulates

0.576

Mnk1 was phosphorylated and activated in vitro by erk1 and p38 map kinasespreliminary results showed that thr344 at least was one of the major sites phosphorylated by erk1

SIGNOR-48360

O14965

P14635

1

phosphorylation

up-regulates activity

0.576

A second wave of Cyclin B1-CDK1 phosphorylation by AurA occurs in late prophase.|Simultaneously, AurA activates and targets the Cyclin B1-CDK1 complex at centrosomes [ xref ].

SIGNOR-280186

P07949

Q8TEW6

1

binding

up-regulates

0.576

We identified two new family members, dok-4 and dok-5, that can directly associate with y1062 of c-ret dok-4 and dok-5 enhance c-ret-dependent activation of mitogen-activated protein kinase

SIGNOR-109513

P29350

P10721

1

binding

down-regulates

0.576

Shp-1 binds and negatively modulates the c-kit receptor by interaction with tyrosine 569 in the c-kit juxtamembrane domain.

SIGNOR-56104

P60484

P35568

1

dephosphorylation

down-regulates activity

0.576

In contrast, IRS-1 level were significantly decreased and phosphorylation of IRS-1 at Ser 307 was strongly enhanced by PTEN knockdown, suggesting that both reduction in IRS-1 level and increase in IRS-1 phosphorylation at Ser307 upon HCV infection occurred in a PTEN dependent manner.|In contrast, IRS-1 level were significantly decreased and phosphorylation of IRS-1 at Ser-307 was strongly enhanced by PTEN knockdown, suggesting that both reduction in IRS-1 level and increase in IRS-1 phosphorylation at Ser307 upon Hepatitis C virus infection occurred in a PTEN-dependent manner.

SIGNOR-277078

P22681

Q8WU20

1

ubiquitination

down-regulates

0.576

The experiments presented in this report illustrate that in response to fgf stimulation, cbl is recruited by grb2 binding to the frs2_ multiprotein complex, resulting in ubiquitination of frs2_ and fgfr. grb2 functions as a link between frs2_ and cbl;grb2 is bound to tyrosine-phosphorylated frs2_ by means of its sh2 domain and to a proline-rich region in the c terminus of cbl by means of its sh3 domains.

SIGNOR-87166

P54727

P27694

1

binding

up-regulates activity

0.575

GG-NER is initiated by the GG-NER specific factor XPC-RAD23B, in some cases with the help of UV-DDB (UV-damaged DNA-binding protein). TC-NER is initiated by RNA polymerase stalled at a lesion with the help of TC-NER specific factors CSA, CSB, and XAB2. Both pathways require the core NER factors to complete the excision process|The core NER dual incision reaction has been reconstituted in vitro with purified factors using XPC-RAD23B, TFIIH, XPA, RPA, XPG, and ERCC1-XPF (Aboussekhra et al. 1995; Mu et al. 1995; Araujo et al. 2000).|The core NER dual incision reaction has been reconstituted in vitro with purified factors using XPC-RAD23B, TFIIH, XPA, RPA, XPG, and ERCC1-XPF (Aboussekhra et al. 1995; Mu et al. 1995; Araujo et al. 2000). Functional studies revealed that XPC-RAD23B is the initial damage recognition factor in this system, as the presence of XPC-RAD23B is required for assembly of the other core NER factors and progression through the NER pathway both in vitro and in vivo

SIGNOR-275698

P06241

P16885

1

phosphorylation

up-regulates activity

0.575

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

SIGNOR-249340

Q13131

Q9UBK2

1

phosphorylation

up-regulates activity

0.575

Ampk phosphorylates pgc-1alpha directly both in vitro and in cells. These direct phosphorylations of the pgc-1alpha protein at threonine-177 and serine-538.

SIGNOR-156780

P18031

Q13882

1

dephosphorylation

down-regulates activity

0.575

Using a variety of PTEN mutant constructs, we show that protein phosphatase activity of PTEN targets PTK6, with efficiency similar to PTP1B, a phosphatase that directly dephosphorylates PTK6 Y342.

SIGNOR-277082

P10275

O15393

1

transcriptional regulation

up-regulates quantity by expression

0.575

The prostate-specific TMPRSS2 gene, while upregulated by AR activity in luminal cells, is also transcribed in basal populations, confirming that AR acts as an expression modulator.

SIGNOR-253687

P24941

O15350

1

phosphorylation

down-regulates activity

0.575

Cyclin-dependent kinases phosphorylate p73 at threonine 86 in a cell cycle-dependent manner and negatively regulate p73.Furthermore, cyclin a/cdk1/2, cyclin b/cdk1/2, and cyclin e/cdk2 complexes can phosphorylate multiple p73 isoforms in vitro at threonine 86.

SIGNOR-99746

P27348

P30307

1

relocalization

down-regulates

0.575

Cdc25c: nuclear exclusion/cytoplasmic sequestration via binding to 14-3-3 proteins.

SIGNOR-163237

Q01453

P25189

1

binding

up-regulates activity

0.575

Our data provide the first direct evidence for the formation of P0–PMP22 complexes at the plasma membrane. These protein interactions probably participate in holding adjacent Schwann cell membranes together and in stabilizing myelin compaction.

SIGNOR-251898

P35222

Q01860

1

binding

up-regulates activity

0.575

We provide evidence suggesting that Beta-catenins interaction with the pluripotency regulator Oct-4 at least partially underlies its effects on sustaining pluripotency.

SIGNOR-241981

Q9ULV1

Q92997

1

binding

up-regulates activity

0.575

Through study of FZD4 and its associated ligand Norrin, we report that a minimum of three residues distal to the KTXXXW motif in the C-terminal tail of Frizzled-4 are essential for DVL recruitment and robust Lef/Tcf-dependent transcriptional activation in response to Norrin.

SIGNOR-258961

Q8NBL1

Q04721

1

binding

up-regulates

0.575

O-glucosylation of epidermal growth factor-like (egf) repeats in the extracellular domain of notch is essential for notch function. O-glucose can be elongated by xylose to the trisaccharide, xylalfa1-3xylalfa1-3glcbeta1-o-ser, whose synthesis is catalyzed by the consecutive action of three glycosyltransferases. A udp-glucose:protein o-glucosyltransferase (poglut/rumi) transfers o-glucose to serine within the o-glucose consensus.

SIGNOR-198716

P06493

Q15910

1

phosphorylation

down-regulates

0.575

Cdk1, which phosphorylates ezh2 at threonines 345 and 487.Phosphorylation of thr-345 and thr-487 promotes ezh2 ubiquitination and subsequent degradation by the proteasome

SIGNOR-174058

P06493

P62136

1

phosphorylation

down-regulates activity

0.575

Both of these pp1 isoforms contain an arg-pro-ile/val-thr-pro-pro-arg sequence near the c terminus, a known site of phosphorylation by cdc/cdk kinases, and phosphorylation attenuates phosphatase activity.

SIGNOR-151799

P46937

Q15797

1

binding

up-regulates

0.575

Yap binds to the phosphorylated smad1 to activate gene transcription.

SIGNOR-201462

P29590

O95405

1

binding

up-regulates

0.574

Cytoplasmic pml physically interacts with smad2/3 and sara (smad anchor for receptor activation) and is required for association of smad2/3 with sara and for the accumulation of sara and tgf-beta receptor in the early endosome.

SIGNOR-128744

Q14344

P61586

1

binding

up-regulates

0.574

Ga12/13 recruitment of rho-gefs causes rhoa activation and f-actin assembly, which promotes lats1/lat2 inactivation by an unknown, but myosin-independent mechanism.

SIGNOR-192111

O14757

O75461

1

phosphorylation

down-regulates activity

0.574

the checkpoint kinase Chk1 phosphorylates E2F6 leading to its dissociation from promoters.

SIGNOR-266371

P00750

P00747

2

binding

up-regulates activity

0.574

The conversion of plasminogen to plasmin can occur by several different mechanisms, but it appears that the most important in uiuo activator is tPA (2). tPA, M, = 70,000, is present in plasma as a single-chain serine protease, but proteolytic cleavage of the Agr275-Ile276 bond in tPA by plasmin yields a disulfide-linked two-chain enzyme

SIGNOR-263533

Q05397

P63000

1

phosphorylation

up-regulates activity

0.574

Both Src and FAK phosphorylate Rac1 at tyrosine 64.|Our investigations of direct interactions between Rac1, Src, and FAK were motivated by our previous insights into FAK augmentation of Rac1 activation during cell spreading, and the Cerione lab 's work on the interactions between Src and Cdc42 , .

SIGNOR-279652

Q13217

Q9P2K8

1

binding

down-regulates activity

0.574

we show that p58IPK is a general inhibitor of the eIF2 kinases in that it also interacts with GCN2

SIGNOR-246204

P06241

P43403

1

phosphorylation

up-regulates activity

0.574

Subsequently, Lck and Fyn phosphorylate and activate the Syk family kinase ZAP-70 when it is recruited to the phosphorylated ITAM motifs xref .

SIGNOR-279043

Q05397

P12814

2

phosphorylation

down-regulates activity

0.574

The cytoskeletal/non-muscle isoform of alpha-actinin is phosphorylated on its actin-binding domain by the focal adhesion kinase tyrosine 12 is the site of phosphorylation. The wild type recombinant protein was not phosphorylated in cells lacking the focal adhesion kinase (fak).Tyrosine phosphorylation reduced the amount of alpha-actinin that cosedimented with actin filaments.

SIGNOR-108329

Q13546

Q8N5C8

1

binding

up-regulates activity

0.574

Tab2 and tab3 activate the jun n-terminal kinase and nuclear factor-kappab pathways through the specific recognition of lys 63-linked polyubiquitin chains by its npl4 zinc-finger (nzf) domain.

SIGNOR-161787

P41279

Q02750

1

phosphorylation

up-regulates

0.574

Activation of mek family kinases requires phosphorylation of two conserved ser/thr residues.Phosphopeptide analysis demonstrated that serine residues 218 and 222 of human mek1 are the primary sites for phosphorylation by c-raf

SIGNOR-36453

P21731

Q14344

1

binding

up-regulates activity

0.574

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-257139

Q92918

Q16584

1

phosphorylation

up-regulates

0.574

Hpk1 also phosphorylated mlk-3 activation loop in vitro, and ser281 was found to be the major phosphorylation site, indicating that hpk1 also activates mlk-3 via phosphorylation of the kinase activation loop.

SIGNOR-83415

Q00535

P37231

1

phosphorylation

down-regulates activity

0.574

CDK5 in turn phosphorylates PPARgamma at Ser273 and prevents the transcription of specific PPARgamma target genes that have anti-diabetic effects .

SIGNOR-278189

O43541

Q13485

1

binding

down-regulates activity

0.574

On the other hand, Smad6 competes with R-Smad and forms a non-functional complex with Smad4, which will inhibit BMP signaling in bone formation. Smad6 is involved in a negative feedback loop regulating BMP signaling and is required to limit BMP signaling during endochondral bone formation.

SIGNOR-195648

P00747

P00750

2

cleavage

up-regulates activity

0.574

The conversion of plasminogen to plasmin can occur by several different mechanisms, but it appears that the most important in uiuo activator is tPA (2). tPA, M, = 70,000, is present in plasma as a single-chain serine protease, but proteolytic cleavage of the Agr275-Ile276 bond in tPA by plasmin yields a disulfide-linked two-chain enzyme

SIGNOR-263534

Q86TM6

Q15011

1

binding

up-regulates activity

0.574

FAM8A1 enhances binding of Herp to Hrd1, an interaction that is required for ERAD. Our findings support a model of Hrd1 complex formation, where the Hrd1 cytoplasmic domain and FAM8A1 have a central role in the assembly and activity of this ERAD machinery. A conserved Hrd1 cytoplasmic domain interacts with FAM8A1 and Herp

SIGNOR-261349

P12814

Q05397

2

binding

down-regulates activity

0.574

Consistent with the results obtained with COS-7 cells, coexpression of wild-type Œ±-actinin with PTP 1B in PTP 1B-null cells resulted in Src/Œ±-actinin binding and limited the interaction between FAK and Src

SIGNOR-261799

Q92831

Q06413

1

binding

up-regulates

0.573

The cofactors grip-1, cbp/p300 and pcaf have hat activity and function as co-activators for mef-2c during myogenesis.

SIGNOR-84032

O00444

Q15154

1

phosphorylation

up-regulates activity

0.573

Plk4‚Äêmediated phosphorylation of PCM1 at S372 is critical for the proper localisation of centriolar satellites, its dimer formation and interaction with other satellite components|Therefore, Plk4 is responsible for PCM1 phosphorylation at S372.

SIGNOR-279556

O15530

Q02156

1

phosphorylation

up-regulates

0.573

In the present study, we analysed the contribution of the phosphoinositide-dependent kinase 1 (pdk-1) and pkcepsilon kinase activity in controlling the phosphorylation of thr(566) and ser(729). pdk-1 phosphorylation of the activation loop triggers autophosphorylation of the hydrophobic motif

SIGNOR-117320

Q15831

Q96EB6

1

phosphorylation

up-regulates activity

0.573

Resveratrol promotes the binding between LKB1 and Sirt1, which we first reported, and this binding leads to LKB1-mediated phosphorylation of Sirt1 at three different serine residues in the C terminus of Sirt1. Mechanistically, LKB1-mediated phosphorylation increases intramolecular interactions in Sirt1, such as the binding of the C terminus to the deacetylase core domain, thereby eliminating DBC1 (Deleted in Breast Cancer 1, Sirt1 endogenous inhibitor) inhibition and promoting Sirt1-substrate interaction.

SIGNOR-277323

Q02156

Q86XR7

1

phosphorylation

up-regulates

0.573

Here we show that tram is transiently phosphorylated by pkcepsilon on serine-16 our study provides a possible target for these molecules in lps signaling. Dag may activate pkc?, Leading to the phosphorylation and activation of tram.

SIGNOR-146991

O14842

P50148

1

binding

up-regulates activity

0.573

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-257272

P20749

Q00653

1

binding

up-regulates

0.573

The cyclin d1 elevation is caused not by increased p65/p50 action but rather by increased nuclear activity of bcl-3-associated nf-kappab p50 and p52.

SIGNOR-146768

Q13526

P01106

1

binding

up-regulates

0.573

Pin1 prolyl isomerase enhances recruitment of serine 62-phosphorylated myc and its coactivators to select promoters during gene activation.

SIGNOR-202134

Q14814

P23409

1

transcriptional regulation

up-regulates quantity by expression

0.573

Myogenin and MEF2 function synergistically to activate the MRF4 promoter during myogenesis.

SIGNOR-238715

P35348

P29992

1

binding

up-regulates activity

0.573

In this report, we demonstrate that in transfected cos-7 cells Gal4 and Ga16, like Gaq and Ga11, can activate PIPLC j3l and that all three al-ARs, alA, alB and alC, can activate endogenous PI-PLC by coupling to Gaq or Ga11.

SIGNOR-278121

Q9BW19

Q02224

1

binding

up-regulates activity

0.573

We found that KIFC1 could directly bind to CENPE in SKOV3 cells (Figure 4C, 4D).

SIGNOR-266116