GleghornLab/Signor_3class · Datasets at Hugging Face

IdA stringlengths 6 21	IdB stringlengths 6 21	labels int64 0 2	mechanism stringclasses 40 values	effect stringclasses 10 values	score float64 0.1 0.99 ⌀	sentence stringlengths 10 1.63k ⌀	signor_id stringlengths 12 14
Q86UR1	Q5TCZ1	2	binding	up-regulates activity	0.409	Tks4 and Tks5 bind NoxA1 through their SH3 domains in a Rac-independent manner\|NoxO1 is required for full Nox1 and Nox3 oxidase activity at least partially because of its role in the plasma membrane recruitment of the NoxA1 activator protein\|Tks4 and Tks5 support Nox1- and Nox3-dependent ROS generation	SIGNOR-264708
P28482	Q9NRA0	1	phosphorylation	up-regulates	0.451	Sphingosine kinase type 2 activation by erk-mediated phosphorylation. site-directed mutagenesis indicated that hsphk2 is phosphorylated on ser-351 and thr-578 by erk1	SIGNOR-153383
P48764	Q13237	0	phosphorylation	down-regulates activity	0.377	CGMP and cGKII increased NHE3 phosphorylation at three sites (rabbit Ser (554), Ser (607), and Ser (663), equivalent to mouse Ser (552), Ser (605), and Ser (659)), all of which had to be present at the same time for cGMP to inhibit NHE3.\|cGMP and cGKII rapidly inhibited NHE3, which was associated with reduced surface NHE3.	SIGNOR-280096
P49841	O15516	1	phosphorylation	down-regulates quantity by destabilization	0.341	We have identified a conserved cluster of serines that include, Ser431, which is a prerequisite phosphorylation site for the generation of BMAL dependent phospho-primed CLOCK and for the potential GSK-3 phosphorylation at Ser427.	SIGNOR-276270
O14965	Q14CS0	2	binding	down-regulates activity	0.304	The UBXN-2/p37/p47 adaptors of CDC-48/p97 regulate mitosis by limiting the centrosomal recruitment of Aurora A.\|We found that UBXN-2 and CDC-48 coimmunoprecipitated with AIR-1 from embryonic extracts	SIGNOR-265042
Q8IVP5	Q96HS1	0	dephosphorylation	up-regulates activity	0.627	Here, we identify that the mitochondrially localized PGAM5 phosphatase interacts with and dephosphorylates FUNDC1 at serine 13 (Ser-13) upon hypoxia or carbonylcyanide p-trifluoromethoxyphenylhydrazone (FCCP) treatment. Dephosphorylation of FUNDC1 catalyzed by PGAM5 enhances its interaction with LC3, which is abrogated following knockdown of PGAM5 or the introduction of a cell-permeable unphosphorylated peptide encompassing the Ser-13 and LIR of FUNDC1. We further observed that CK2 phosphorylates FUNDC1 to reverse the effect of PGAM5 in mitophagy activation.	SIGNOR-273654
Q9H0Z9	P49841	0	phosphorylation	down-regulates	0.2	Here, we showed that rnpc1 is phosphorylated at ser195 by glycogen synthase kinase 3 (gsk3). We also provided evidence that ser195 phosphorylation converts rnpc1 from a repressor to an activator of p53.	SIGNOR-203011
O95166	Q9NT62	2	binding	up-regulates activity	0.847	Three human atg8 (hatg8) homologs, lc3, gabarap, and gate-16, have been characterized as modifiers in reactions mediated by hatg7 (an e1-like enzyme) and hatg3 (an e2-like enzyme)	SIGNOR-141868
P04049	Q8IVT5	2	binding	up-regulates activity	0.654	In mammals, RAF family kinases include three catalytically competent enzymes (ARAF, BRAF and CRAF) and two pseudokinases (KSR1 and KSR2) that have been described as scaffolds owing to their apparent ability to bridge RAF isoforms and their substrate, mitogen-activated protein kinase kinase (MEK).Kinase suppressor of Ras (KSR) pseudokinases were also shown to dimerize with kinase-competent RAFs to stimulate catalysis allosterically.	SIGNOR-273880
Q14247	P12931	0	phosphorylation	down-regulates activity	0.801	Erk phosphorylation and a mimicking S405,418D double mutation enhanced cortactin binding and activation of N-WASP. In contrast, Src phosphorylation inhibited the ability of cortactin previously phosphorylated by Erk, and that of S405,418D double mutant cortactin, to bind and activate N-WASP. Furthermore, Y-->D mutation of three tyrosine residues targeted by Src (Y421, Y466, and Y482) inhibited the ability of S405,418D cortactin to activate N-WASP.	SIGNOR-246513
P12757	Q99717	2	binding	down-regulates	0.448	Ski also represses bmp signaling through interactions with smad4 and bmp-specific r-smads, smad1 or smad8.	SIGNOR-95474
Q13467	O75197	2	binding	up-regulates activity	0.67	Here we report that Wnt receptor Frizzled (Frz) and theco-receptors LRP5 and LRP6 (LRP5/6) directly interact with each other and this interaction is regulated by the LRP6 ectodomain.	SIGNOR-258969
Q13133	Q9C0F0	2	binding	down-regulates activity	0.2	We determined that ASXL3 depletion augments the ligand-induced transcriptional activities of LXRα and TRβ, which were repressed by ASXL3 overexpression. The ligand-dependent interactions of ASXL3 with LXRα and TRβ were demonstrated by the GST pull-down and immunoprecipitation analyses. We confirmed that ASXL3 suppresses the expression of LXRα target genes through its recruitment to the LXR-response elements.	SIGNOR-266765
P08670	Q96GD4	0	phosphorylation	down-regulates	0.423	By identifying eight aurora-b phosphorylation sites on vimentin in vitro, we have demonstrated that vimentin-ser-72 is an in vitrophosphorylation site of aurora-b. in vitro analyses revealed that aurora-b phosphorylates vimentin at approximately 2 mol phosphate/mol of substrate for 30 min and that this phosphorylation dramatically inhibits vimentin filament formation.	SIGNOR-96057
Q99683	O95382	2	binding	up-regulates quantity by stabilization	0.551	C-terminal region of ASK1 binds to ASK2 and inhibits the degradation of ASK2	SIGNOR-260831
O14519	P24941	2	binding	down-regulates activity	0.441	The ubiquitously expressed CDK2AP1 protein is the only known specific inhibitor of CDK2, making it an important component of cell cycle regulation during G1-to-S phase transition.	SIGNOR-264781
O95863	P31947	0	relocalization	down-regulates	0.2	Pkd1 phosphorylates ser(11) (s11) on transcription factor snail, a master emt regulator and repressor of e-cadherin expression, triggering nuclear export of snail via 14-3-3_ binding	SIGNOR-168540
P62714	Q9UIC8	0	methylation	up-regulates activity	0.661	Methylation of the carboxy-terminal Leu309 in a conserved TPDYFL309 motif of the C subunit has been shown to enhance the affinity of the PP2A core enzyme for some, but not all, regulatory subunits \|The PP2A core enzyme was methylated by a PP2A-specific leucine carboxyl methyltransferase (LCMT1)	SIGNOR-265751
Q8WWM9	Q13309	2	binding	down-regulates quantity by destabilization	0.2	Skp2 induces ubiquitin-dependent degradation of Cygb. To this end, we performed an in vivo ubiquitination assay in HEK293T cells by transfecting relevant plasmids as indicated. The V5-Skp2DN was generated by deleting the N-terminal residues from 1 to 153 containing the F-box domain, which is involved in recruiting Skp2 to the SCF complex.	SIGNOR-272792
P59768	P19174	2	binding	up-regulates	0.2	Furthermore, this work suggested that the gbetagamma subunits released upon gi activation activated phospholipase c-gamma (plc-gamma) to produce inositol 3 phosphate (ip3) which would subsequently increase intracellular ca2+ abundance.	SIGNOR-199138
P28336	O95837	2	binding	up-regulates activity	0.435	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-257422
Q13233	O95819	0	phosphorylation	up-regulates	0.558	Hpk1 binds and phosphorylates mekk1 directly	SIGNOR-44040
P48058	Q9UQM7	0	phosphorylation	up-regulates	0.592	Receptor internalization, altered;intracellular localization	SIGNOR-97546
Q49MG5	P53350	0	phosphorylation	up-regulates	0.275	We also demonstrate that asap is a novel substrate of plk1 phosphorylation and have identified serine 289 as the major phosphorylation site by plk1 in vivo. Asap phosphorylated on serine 289 is localized to centrosomes during mitosis, but this phosphorylation is not required for its plk1-dependent localization at the spindle poles. We show that phosphorylated asap on serine 289 contributes to spindle pole stability in a microtubule-dependent manner	SIGNOR-166564
Q13131	Q16576	1	phosphorylation	up-regulates activity	0.2	AMPK increased HAT1 activity through phosphorylation of HAT1-Ser190 and RBBP7-Ser314\| interaction between RBBP7 and HAT1 is required for acetyltransferase activity	SIGNOR-264784
Q13285	P50613	0	phosphorylation	up-regulates	0.366	In conclusion, our results indicate that cdk7, as part of the cak complex and tfiih, phosphorylates sf1 at s203 followed by increased transcriptional activity of sf1	SIGNOR-157952
Q8WUP2	Q9BQL6	2	binding	up-regulates activity	0.448	Kindlin binds migfilin tandem LIM domains and regulates migfilin focal adhesion localization and recruitment dynamics. Two integrin-binding proteins present in FAs, kindlin-1 and kindlin-2, are important for integrin activation, FA formation, and signaling. By binding filamin, migfilin provides a link between kindlin and the actin cytoskeleton.	SIGNOR-266103
Q03113	Q9GZQ4	2	binding	up-regulates activity	0.25	Here we systematically quantified ligand-induced interactions between 148 GPCRs and all 11 unique G alpha subunit C-termini. For each receptor, we probed chimeric G alpha subunit activation via a transforming growth factor-alpha (TGF alpha) shedding response in HEK293 cells lacking endogenous Gq/11- and G12/13- signaling. \| We defined positive coupling if any member of the subfamily scored LogRAi ≥ -1 and negative coupling if all of the members scored LogRAi < -1 (Figure 3A-B). ROC analysis gives AUC = 0.78 (Figure S4A) when considering high-confidence known coupling data and suggested a threshold of LogRAi ≥ -1.0 for defining true couplings. \| The score associated to this interaction has a LogRAi ≥ -1.0.	SIGNOR-257402
Q03164	Q13535	0	phosphorylation	up-regulates	0.281	Mll is phosphorylated at serine 516 by atr in response to genotoxic stress in the s phase, which disrupts its interaction with, and hence its degradation by, the scf(skp2) e3 ligase, leading to its accumulation.	SIGNOR-25151
P52657	Q06330	2	binding	up-regulates	0.2	Rbp interacts with two transcriptional coactivators: dtafii110, a subunit of tfiid, and tfiia to repress transcription. The domain of dtafii110 targeted by rbp is the same domain that interacts with tfiia	SIGNOR-57832
O60890	P20393	2	binding	up-regulates activity	0.2	Rev-erbα regulates OPHN-1-mediated RhoA/ERM signalling in platelets., The results of the co-immunoprecipitation revealed that Rev-erbα coimmunoprecipitated with OPHN-1 in both mouse and human platelets and this interaction significantly increased upon stimulation with agonist U46619.	SIGNOR-268428
P17252	Q15080	1	phosphorylation	up-regulates activity	0.2	In murine and guinea pig neutrophils, PKCδ is required for the phosphorylation of p40phox, a subunit of the NADPH oxidase complex (Li et al., 2016; Someya et al., 1999). In particular, it mediates phosphorylation of the threonine 154 (T154) residue of p40phox, a key regulatory step in the activation of the NADPH oxidase complex in peripheral neutrophils and B cells, in both mice and humans. In conclusion, the EBV-B cells of patients with PKCδ deficiency have impaired ROS production, associated with lower levels of phosphorylation of the cytosolic NADPH oxidase subunit p40phox by PKCδ.	SIGNOR-277628
Q99835	P23771	1	null	up-regulates activity	0.2	That GATA is a downstream effector of the hedgehog pathway.	SIGNOR-253527
P04141	Q99062	2	binding	up-regulates	0.591	A g-csfr expression plasmid was introduced into interleukin-3 (il-3)-dependent mouse myeloid precursor fdc-p1 cells that normally do not respond to g-csf. G-csf stimulated proliferation of the transformants these results suggested that the g-csfr, but not the il-3/gm-csf receptors, transduced the neutrophilic differentiation signal into cells.	SIGNOR-31963
Q13976	P19429	1	phosphorylation	up-regulates activity	0.357	Phosphorylation at ser 23/24 (e.g., by pka or pkg) results in reduction in myofilament ca2+ sensitivity and an increase in crossbridge cycling rate, leading to acceleration of relaxation and an increase in power output but a reduced economy of contraction. Conversely, phosphorylation at ser 43/45 (by pkc) is associated with reduced maximum ca2+-activated force and decreased crossbridge cycling rates, which are likely to reduce power output and delay relaxation, with an increased economy of contraction.	SIGNOR-134644
P12814	P18031	0	dephosphorylation	up-regulates	0.335	Here we report that protein-tyrosine phosphatase 1b (ptp 1b) is an ?-Actinin phosphatase.	SIGNOR-141634
P19086	O43614	2	binding	up-regulates activity	0.25	Here we systematically quantified ligand-induced interactions between 148 GPCRs and all 11 unique G alpha subunit C-termini. For each receptor, we probed chimeric G alpha subunit activation via a transforming growth factor-alpha (TGF alpha) shedding response in HEK293 cells lacking endogenous Gq/11- and G12/13- signaling. \| We defined positive coupling if any member of the subfamily scored LogRAi ≥ -1 and negative coupling if all of the members scored LogRAi < -1 (Figure 3A-B). ROC analysis gives AUC = 0.78 (Figure S4A) when considering high-confidence known coupling data and suggested a threshold of LogRAi ≥ -1.0 for defining true couplings. \| The score associated to this interaction has a LogRAi ≥ -1.0.	SIGNOR-257124
O95477	P00533	0	phosphorylation	down-regulates quantity by destabilization	0.295	We further provide in vitro evidence that epidermal growth factor receptor (EGFR)-mediated phosphorylation regulated ABCA1 ubiquitination \|The EGFR selective inhibitor PD168393 blocked the EGFR-ABCA1 interaction and abolished ABCA1Ser2054 phosphorylation\|	SIGNOR-264419
P35499	Q96PU5	0	ubiquitination	down-regulates quantity by destabilization	0.279	The control of Nav density at the cell membrane is crucial to ensuring normal neuronal excitability. Navs are subject to posttranslational modifications that may influence their cell membrane availability. Ubiquitylation is a key process that orchestrates the internalization and subsequent degradation or recycling of Navs. This is accomplished by ubiquitin protein ligases, such as NEDD4-2 (neuronal precursor cell expressed developmentally downregulated-4 type 2).	SIGNOR-253460
O43318	O00743	0	dephosphorylation	down-regulates activity	0.372	Protein phosphatase 6 down-regulates TAK1 kinase activation in the IL-1 signaling pathway\|From proteomic analysis of TAK1-binding proteins, we identified protein phosphatase 6 (PP6), a type-2A phosphatase, and demonstrated that PP6 associated with and inactivated TAK1 by dephosphorylation of Thr-187.	SIGNOR-248292
P06241	Q05655	1	phosphorylation	up-regulates activity	0.597	In conclusion, our in vitro data and previous report ( xref ) demonstrate that Fyn phosphorylation of Y311 on PKC\u03b4 activates the apoptotic signaling cascade in DAergic neurons in response to neurotoxic insults.	SIGNOR-279737
O00743	Q8N884	1	dephosphorylation	down-regulates activity	0.2	In this study, we found that PPP6C suppressed phosphorylation of human cGAS (hcGAS) at S435 or mouse cGAS (mcGAS) at S420 in its substrate-binding pocket, thus preventing its binding to GTP and inhibiting the synthesis of cGAMP.\|These data suggest that PPP6C inhibits cGAS activity.	SIGNOR-276990
Q9HAU4	O95630	1	polyubiquitination	down-regulates quantity by destabilization	0.529	RNF11 recruits AMSH to Smurf2 E3 ligase. Smurf2 promotes ubiquitination of AMSH in the presence of wt RNF11. Previously, we have shown that RNF11 interacts with the HECT-type E3 ligases AIP4 and Smurf2. Here, we show that RNF11 binds to AMSH in mammalian cells and that this interaction is independent of the RNF11 RING-finger domain and the PY motif. Our results also demonstrate that AMSH is ubiquitinated by Smurf2 E3 ligase in the presence of RNF11 and that a consequent reduction in its steady-state level requires both RNF11 and Smurf2. RNF11 therefore recruits AMSH to Smurf2 for ubiquitination, leading to its degradation by the 26S proteasome.	SIGNOR-272951
Q02156	Q16612	1	phosphorylation	down-regulates quantity by destabilization	0.2	Site-directed mutagenesis of S59A retarded P311 degradation and induced glioma cell motility. In contrast, S59D mutation resulted in the rapid degradation of P311 and reduced glioma cell migration.Taken together, our results show that the serine phosphorylation of P311 is dependent on the function of both PKCε and PKCz.	SIGNOR-273830
P16885	Q92835	0	dephosphorylation	down-regulates activity	0.312	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-268455
P21796	Q5TGU0	2	binding	up-regulates activity	0.309	Our results demonstrate the existence of a VDAC-TSPO2-ANT complex that mediates ATP release from RBCs. We previously demonstrated that the translocase protein TSPO2 together with the voltage-dependent anion channel (VDAC) and adenine nucleotide transporter (ANT) were involved in a membrane transport complex in human red blood cells (RBCs). . The present results show that TSPO ligands induce polymerization of VDAC, coupled to activation of ATP release by a supramolecular complex involving VDAC, TSPO2 and ANT.	SIGNOR-261826
Q9UM73	Q14469	1	phosphorylation	up-regulates activity	0.266	NPM-ALK also directly phosphorylates HES1 protein.	SIGNOR-280181
O14920	P35568	1	phosphorylation	down-regulates activity	0.654	IRS-1 is a novel direct substrate for IKK and that phosphorylation of IRS-1 at Ser(312) (and other sites) by IKK may contribute to the insulin resistance mediated by activation of inflammatory pathways.	SIGNOR-251297
Q15233	P11387	2	binding	up-regulates	0.373	We show that the psf/p54 dimer has pronounced stimulatory effect on dna catalysis by topoisomerase i	SIGNOR-60557
Q00535	P30086	1	phosphorylation	down-regulates quantity by destabilization	0.337	Here, we demonstrate that RKIP is a substrate of cyclin-dependent kinase 5 (CDK5) in neurons and that the phosphorylation of RKIP at T42 causes the release of Raf-1. Moreover, T42 phosphorylation promotes the exposure and recognition of the target motif "KLYEQ" in the C-terminus of RKIP by chaperone Hsc70 and the subsequent degradation of RKIP via chaperone-mediated autophagy (CMA).	SIGNOR-276672
Q14258	Q15911	1	polyubiquitination	down-regulates quantity by destabilization	0.451	In the present study we show that EFP (oestrogen-responsive finger protein) is an E3 ubiquitin ligase mediating oestrogen-induced ATBF1 protein degradation. Knockdown of EFP increases ATBF1 protein levels, whereas overexpression of EFP decreases ATBF1 protein levels.	SIGNOR-272048
O14939	P52333	0	phosphorylation	up-regulates	0.407	We identified three kinases capable of phosphorylating pld2 in vitro-epidermal growth factor receptor (egfr), jak3, and src (with jak3 reported for the first time in this study)-that phosphorylate an inhibitory, an activator, and an ambivalent (one that can yield either effect) site, respectively. Mass spectrometry analyses indicated the target of each of these kinases as y(296) for egfr, y(415) for jak3, and y(511) for src.	SIGNOR-163858
O75381	Q92968	2	binding	up-regulates activity	0.92	Pex14 interacts via its proline-rich motif with the SH3 domain of Pex13. We conclude that the association of Pex13 with Pex14 is an essential step in peroxisomal protein import	SIGNOR-253029
Q8IZP0	P22681	2	binding	up-regulates	0.371	Here we uncover a novel interaction between abi-1 and the cbl ubiquitin ligase and show that abi-1 mediates cbl accumulation to the plasma membrane upon stimulation by egf.	SIGNOR-154162
O15068	P60953	1	guanine nucleotide exchange factor	up-regulates activity	0.751	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-260560
Q96SN8	Q13257	1	transcriptional regulation	up-regulates quantity by expression	0.309	These data indicate that CDK5RAP2 is a positive regulator of both the BUBR1 promoter and the MAD2 promoter	SIGNOR-260313
P38435	O43852	2	binding	down-regulates activity	0.401	Results are presented that demonstrate that the endoplasmic reticulum chaperone protein calumenin is associated with gamma-carboxylase and inhibits its activity.	SIGNOR-265910
P17612	P17655	1	phosphorylation	down-regulates	0.262	Activation of m-calpain (calpain ii) by epidermal growth factor is limited by protein kinase a phosphorylation of m-calpain.These Data point to a novel mechanism of negative control of calpain activation, direct phosphorylation by pka.	SIGNOR-116248
O00273	O76075	2	binding	down-regulates	0.929	Dff is a heterodimer of 40 kda and 45 kda subunits.	SIGNOR-29729
Q9UNH5	P30291	1	dephosphorylation	up-regulates quantity by stabilization	0.545	In particular, we found that Cdc14A inhibits Wee1 degradation through the dephosphorylation of Ser-123 and Ser-139 residues.	SIGNOR-267470
O96017	P30307	1	phosphorylation	down-regulates activity	0.856	Activated chk2 in turn phosphorylates cdc25c at serine-216 contributing to the g2/m checkpoints. Cds1 phosphorylates and inactivates cdc25 in vitro\|CDC25C is phosphorylated on Ser 216 throughout interphase, but not in mitosis. This creates a binding site for 14‐3‐3 proteins \| It has been suggested that 14‐3‐3 protein binding is responsible for retaining Cdc25C in the cytoplasm during interphase, thereby contributing to the prevention of premature initiation of mitotic events	SIGNOR-102779
Q9Y4C4	O43164	0	ubiquitination	up-regulates activity	0.403	These results suggest that the ubiquitylation of MFHAS1 by praja2 has a vital role in M1 macrophage polarization and promotes the transformation of M2 macrophages to M1 macrophages through both the JNK and p38 pathways.	SIGNOR-278559
Q16584	P24941	0	phosphorylation	up-regulates activity	0.2	Using in vitro kinase assays and phosphomutants, we determined that CDK1 phosphorylates MLK3 on Ser548 and decreases MLK3 activity during mitosis, whereas CDK2 phosphorylates MLK3 on Ser770 and increases MLK3 activity during G1/S and G2 phases.	SIGNOR-277604
Q92547	O60671	2	binding	up-regulates	0.619	The 9-1-1 complex functions as a clamp, encircling the dna, and recruits the brct domain-containing protein topbp1 in a phospho-dependent manner	SIGNOR-179379
Q13418	P49841	1	phosphorylation	down-regulates activity	0.69	ILK can also directly phosphorylates GSK-3\u03b2 at Ser 9, inactivate it, and lead to activation of some transcription factors [ ].\|ILK knockdown activates GSK-3beta.	SIGNOR-278252
P68400	P28482	0	phosphorylation	up-regulates	0.369	Erk2, which is activated by egfr signaling, directly binds to ck2alpha via the erk2 docking groove and phosphorylates ck2alpha primarily at t360/s362, subsequently enhancing ck2alpha activity	SIGNOR-161855
P27361	P49418	1	phosphorylation	down-regulates activity	0.274	Thus, we propose that mapk phosphorylation of amphiphysin1 controls ngf receptor/trka-mediated endocytosis by terminating the amphiphysin1-ap-2 interaction.Our results indicate that phosphorylation of amphiphysin 1 at ser-285 and/or ser-293 affects the function of amphiphysin1.Mapk phosphorylation of ser-285 and ser-293 could modulate the interaction between prd and ap-2, resulting in the dissociation of amphiphysin1 from ap-2.	SIGNOR-126867
Q9H4B4	P11388	1	phosphorylation	up-regulates	0.268	The direct phosphorylation of thr(1342) of topoisomerase iialpha by plk3 was demonstrated with an in vitro kinase assay, and overexpression of plk3 induced the phosphorylation of thr(1342) in cellular topoisomerase iialpha. it is possible that plk3 regulates the activity of topoisomerase iia by phosphorylation in a cell-cycle dependent manner. Another possibility is that plk3 regulates the activity of topoisomerase iia when the checkpoint is activated.	SIGNOR-159596
Q05655	P04637	1	phosphorylation	up-regulates	0.677	Here, we show that the pro-apoptotic kinase, protein kinase c delta (pkcdelta), is involved in phosphorylation of p53 on ser(46). pkcdelta potentiates p53-dependent apoptosis by ser(46) phosphorylation in response to genotoxic stress.	SIGNOR-143382
O75506	Q00613	2	binding	down-regulates activity	0.699	HSBP1 is nuclear-localized and interacts in vivo with the active trimeric state of HSF1 that appears during heat shock. During attenuation of HSF1 to the inert monomer, HSBP1 associates with Hsp70. HSBP1 negatively affects HSF1 DNA-binding activity, and overexpression of HSBP1 in mammalian cells represses the transactivation activity of HSF1. HSF1 interacts with HSBP1 in vivo and is a nuclear localized protein.	SIGNOR-261181
P50052	P50148	2	binding	up-regulates	0.504	These neuropeptide gpcrs are coupled to the activation of phospholipase c, and therefore to calcium ele- vation and protein kinase c (pkc) activation, through g proteins of the alfaq family	SIGNOR-106995
P14921	Q99684	2	binding	down-regulates activity	0.426	Co-immunoprecipitation analyses and glutathione-S-transferase pull-down assays revealed that ETS1 bound directly to GFI1 via its Ets domain, and GFI1 bound to ETS1 via its zinc-finger domain. Luciferase (Luc) assays using artificial reporters showed that GFI1 repressed ETS1-mediated transcriptional activation and ETS1 repressed GFI1-mediated transcriptional activation, in a dose-dependent manner.	SIGNOR-254202
P04629	A7KAX9	1	relocalization	up-regulates	0.602	Grit translocation was regulated by receptor stimulation	SIGNOR-95809
Q16539	P35236	2	phosphorylation	down-regulates activity	0.59	The noncatalytic N terminus of HePTP binds Erk and p38 and is phosphorylated at Ser-72 and Thr-45 by these kinases. the N terminus of HePTP binds Erk and p38 but may release them upon phosphorylation.it is clear that phosphorylation of HePTP at Thr-45 and/or Ser-72 is not required for inhibition of MAP kinase. Rather, it seems that phosphorylation has the opposite effect, namely to lessen the inhibitory effect of HePTP.	SIGNOR-250109
Q9Y613	P60709	2	binding	up-regulates quantity by stabilization	0.344	Fhos, a mammalian formin, directly binds to F-actin via a region N-terminal to the FH1 domain and forms a homotypic complex via the FH2 domain to promote actin fiber formation	SIGNOR-276613
Q92558	O43295	2	binding	up-regulates	0.553	Wrp binds directly to wave-1 through its src homology domain 3 and specifically inhibits rac function in vivo.	SIGNOR-95967
Q93097	Q9NPG1	2	binding	up-regulates	0.63	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-131777
P20393	Q9UBK2	0	transcriptional regulation	up-regulates quantity by expression	0.522	Transcriptional coactivator PGC-1α integrates the mammalian clock and energy metabolism. Here we show that PGC-1alpha (Ppargc1a), a transcriptional coactivator that regulates energy metabolism, is rhythmically expressed in the liver and skeletal muscle of mice. PGC-1alpha stimulates the expression of clock genes, notably Bmal1 (Arntl) and Rev-erbalpha (Nr1d1), through coactivation of the ROR family of orphan nuclear receptors. Chromatin immunoprecipitation (ChIP) assays in HepG2 cells indicate that PGC-1α is present near RORE on the proximal Bmal1 promoter.These results indicate that PGC-1α activates Bmal1 transcription by altering the local chromatin environment from a repressive to an active state.	SIGNOR-268030
Q8IVM0	P06239	0	phosphorylation	down-regulates activity	0.2	We found that Ymer was considerably phosphorylated on tyrosine residues also via Src family kinases such as Lck. A luciferase reporter assay showed that mutation of tyrosines on Ymer (YmerY217/279/304F) results in loss of the inhibitory activity for NF-kappaB signaling.	SIGNOR-262855
Q04759	Q9BWT7	0	relocalization	up-regulates activity	0.435	TBKBP1 recruits TBK1 to protein kinase C-theta (PKCθ) through a scaffold protein, CARD10. This enables PKCθ to phosphorylate TBK1 at Ser 716, a crucial step for TBK1 activation	SIGNOR-272471
O14920	Q9Y6K9	2	phosphorylation	down-regulates activity	0.962	In this study we analyze the ikkbeta-mediated phosphorylation of the ikk-binding domain of nemo. In vitro, ikkbeta phosphorylates three serine residues in the domain of nemo at positions 43, 68, and 85. However, mutational analysis revealed that only the phosphorylation of serine 68 in the center of the ikk-binding domain plays an essential role for the formation and the function of the ikk complex. Thus, ser(68) phosphorylation attenuates the amino-terminal dimerization of nemo as well as the ikkbeta-nemo interaction. I	SIGNOR-158659
Q92949	Q9UI46	1	transcriptional regulation	up-regulates quantity by expression	0.368	FOXJ1 expression in basal cells induced the expression of a panel of cilia-associated genes, including centrin 2 (CETN2); dynein, axonemal, heavy chain 11 (DNAH11); dynein, axonemal, intermediate chain 1 (DNAI1); dynein, axonemal, light intermediate chain 1 (DNALI1); EF-hand domain, C-terminal, containing 1 (EFHC1); sperm associated antigen 6 (SPAG6); tektin 1 (TEKT1), TEKT2 and tubulin, alpha 1a (TUBA1A; Figure 3C and Additional file 2: Table S1).	SIGNOR-266932
P98164	P16035	2	binding	up-regulates quantity	0.2	We show that megalin/LRP-2 acts as an endocytic receptor for proMMP-2:TIMP-2 complex. We found that RAP, an antagonist of the LDL receptor family18, competed with binding of proMMP-2:TIMP-2 complex onto rat BN16 epithelial cells.	SIGNOR-265254
O60936	P19784	0	phosphorylation	up-regulates activity	0.2	Phosphorylation of ARC at T149 Is Required for Its Antiapoptotic Effect. Here we report that the function of ARC is regulated by protein kinase CK2. ARC at threonine 149 is phosphorylated by CK2. This phosphorylation targets ARC to mitochondria. ARC is able to bind to caspase-8 only when it is localized to mitochondria but not to the cytoplasm.	SIGNOR-262836
Q92831	P15172	2	binding	up-regulates	0.647	Our results provide direct evidence that myod acetylation functionally activates the protein and show that both pcaf and cbp/p300 are candidate enzymes for myod acetylation in vivo	SIGNOR-81059
Q02156	O14649	1	phosphorylation	down-regulates activity	0.2	We have previously shown that carbamylated PAF-induced repolarization abnormalities result from the protein kinase C (PKC) ε-dependent phosphorylation of the two-pore domain potassium channel TASK-1. Further studies identified threonine 383 in the C terminus of human and canine TASK-1 as the phosphorylation site required for PAF-dependent inhibition of the channel.	SIGNOR-276431
P49759	Q07955	1	phosphorylation	up-regulates activity	0.673	In a previous study, we showed that CLK1 phosphorylates SRSF1 to a greater extent than SRPK1, inducing a hyper-phosphorylated state that can be readily detected by a gel shift on SDS-PAGE. xref In xref , the phosphorylation of SRSF1 in single turnover experiments using SRPK1 and CLK1 is shown.\|Unlike SRPK1, CLK1 induces a unique structural form of SRSF1 observed by SDS-PAGE that is exclusively the result of Ser-Pro rather than Arg-Ser phosphorylation.	SIGNOR-279608
P27361	P51170	1	phosphorylation	down-regulates quantity by destabilization	0.28	Using a number of different approaches it was demonstrated that the protein kinase acting on betaThr-613 and gammaThr-623 is the extracellular regulated kinase (ERK). It is suggested that an ERK-mediated phosphorylation of betaThr-613 and gammaThr-623 down-regulates the channel by facilitating its interaction with Nedd4.	SIGNOR-249449
P55211	Q5T447	0	polyubiquitination	down-regulates activity	0.2	HECTD3 binds and ubiquitinates caspase-9.HECTD3 inhibits caspase-9 oligomerization and association with Apaf-1. HECTD3 suppressing caspase-9 activation is dependent on T157 phosphorylation by ERK.	SIGNOR-272329
P09471	P30411	2	binding	up-regulates activity	0.2	Here we systematically quantified ligand-induced interactions between 148 GPCRs and all 11 unique G alpha subunit C-termini. For each receptor, we probed chimeric G alpha subunit activation via a transforming growth factor-alpha (TGF alpha) shedding response in HEK293 cells lacking endogenous Gq/11- and G12/13- signaling. \| We defined positive coupling if any member of the subfamily scored LogRAi ≥ -1 and negative coupling if all of the members scored LogRAi < -1 (Figure 3A-B). ROC analysis gives AUC = 0.78 (Figure S4A) when considering high-confidence known coupling data and suggested a threshold of LogRAi ≥ -1.0 for defining true couplings. \| The score associated to this interaction has a LogRAi ≥ -1.0.	SIGNOR-256974
Q9UBF6	Q13616	2	binding	up-regulates activity	0.857	SAG was found to be the second family member of Rbx (RING box protein) or ROC (Regulator of cullins) or Hrt that is a component of SCF E3 ubiquitin ligase. Indeed, like ROC1/Rbx1/Hrt1, SAG binds to Cul1 and SAG-Cul1 complex has ubiquitin ligase activity to promote poly-ubiquitination of E2/Cdc34.	SIGNOR-271444
Q9UQB8	P63000	2	binding	up-regulates	0.739	Here we demonstrate that irsp53, a substrate for insulin receptor with unknown function, is the 'missing link' between rac and wave. Activated rac binds to the amino terminus of irsp53, and carboxy-terminal src-homology-3 domain of irsp53 binds to wave to form a trimolecular complex.	SIGNOR-85302
Q9H3D4	O94901	1	transcriptional regulation	up-regulates quantity by expression	0.2	Here we show that in the developing skin, epidermal progenitor cells of mice lacking p63 transcription factor display alterations in the nuclear shape accompanied by a marked decrease in expression of several nuclear envelope-associated components (Lamin B1, Lamin A/C, Sun1, Nesprin-3, Plectin) compared with controls. Furthermore, chromatin immunoprecipitation-quantitative PCR assay showed enrichment of p63 on Sun1, Syne3, and Plec promoters, suggesting them as p63 targets.	SIGNOR-263278
Q99626	Q12864	1	transcriptional regulation	up-regulates quantity by expression	0.406	The present study aims to identify the transcription factors which interact and regulate CDH17 promoter activity that might contribute to the up-regulation of CDH17 gene in human HCC\|we identified hepatic nuclear factor 1α (HNF1α) and caudal-related homeobox 2 (CDX2) binding sites at the proximal promoter region which modulate the CDH17 promoter activities in two HCC cell lines (Hep3B and MHCC97L)	SIGNOR-253963
P00519	Q8TDZ2	1	phosphorylation	up-regulates activity	0.312	Biochemical assays revealed Abl phosphorylates Mical to directly amplify Mical Redox-mediated F-actin disassembly.\|We now find that the Abl non receptor protein tyrosine kinase and oncoprotein signaling pathway activates Mical to direct multiple cellular effects - including extending and shaping cellular processes, guiding axons, and orchestrating cancer cell invasion, colony formation, and survival.	SIGNOR-279674
P40198	Q12913	0	dephosphorylation	down-regulates activity	0.387	We also determined that recombinant PTPRJ directly dephosphorylates the cytoplasmic tyrosine residues of purified full-length CEACAM3 and recognizes synthetic CEACAM3-derived phospho-peptides as substrates.\|We show depletion of PTPRJ results in a gain-of-function phenotype, while overexpression of a constitutively active PTPRJ phosphatase strongly reduces bacterial uptake via CEACAM3.	SIGNOR-277091
P56278	Q9Y243	2	binding	up-regulates	0.364	Full-length tcl1 and its isoforms bind to akt / in in vitro kinase assays using gsk-3_ as a substrate, we found that the presence of any of the tcl1 family proteins (tcl1, mtcp1, or tcl1b) as gst fusion proteins significantly enhanced akt-induced gsk-3_ phosphorylation	SIGNOR-81677
P68366	Q5SQI0	0	acetylation	up-regulates quantity by stabilization	0.262	Alpha-Tubulin acetyltransferase (alphaTAT1) is the major α-tubulin lysine-40 (K40) acetyltransferase in mammals, nematodes, and protozoa, and its activity plays a conserved role in several microtubule-based processes.\|The tubulin subunits of microtubules are acetylated, and lysine-40 (K40) of the alpha-tubulin subunit has been identified as an important conserved site of microtubule acetylation (6–8). This modification is considered a hallmark of stable, long-lived microtubules	SIGNOR-272249
P15289	P69905	1	acetylation	up-regulates activity	0.2	ASA acetylates hemoglobin. Purified acetylated hemoglobin had a slightly increased oxygen affinity and decreased heme-heme interaction.	SIGNOR-251773
Q05513	P09211	1	phosphorylation	up-regulates activity	0.2	Peptide phosphorylation analyses and both phosphorylation and enzyme kinetic studies with GSTP1 proteins mutated at candidate amino acid residues established Ser-42 and Ser-184 as putative phospho-acceptor residues for both kinases in the GSTP1 protein. Together, these findings show PKA- and PKC-dependent phosphorylation as a significant post-translational mechanism of regulation of GSTP1 function. Together, these results further support S42 and S184 as major phosphor-acceptor residues for PKA and PKC and suggest that the increased activity of the phospho-GSTP1 was not simply a consequence of the negative charge introduced in the GSTP1 protein by the phosphate group.All eight PKC isoforms, PKC-α, PKC-βI, PKC-βII, PKC-ε, PKC-γ, PKC-η, and PKC-ζ phosphorylated the GSTP1 protein efficiently	SIGNOR-276017

Q86UR1

Q5TCZ1

2

binding

up-regulates activity

0.409

Tks4 and Tks5 bind NoxA1 through their SH3 domains in a Rac-independent manner|NoxO1 is required for full Nox1 and Nox3 oxidase activity at least partially because of its role in the plasma membrane recruitment of the NoxA1 activator protein|Tks4 and Tks5 support Nox1- and Nox3-dependent ROS generation

SIGNOR-264708

P28482

Q9NRA0

1

phosphorylation

up-regulates

0.451

Sphingosine kinase type 2 activation by erk-mediated phosphorylation. site-directed mutagenesis indicated that hsphk2 is phosphorylated on ser-351 and thr-578 by erk1

SIGNOR-153383

P48764

Q13237

0

phosphorylation

down-regulates activity

0.377

CGMP and cGKII increased NHE3 phosphorylation at three sites (rabbit Ser (554), Ser (607), and Ser (663), equivalent to mouse Ser (552), Ser (605), and Ser (659)), all of which had to be present at the same time for cGMP to inhibit NHE3.|cGMP and cGKII rapidly inhibited NHE3, which was associated with reduced surface NHE3.

SIGNOR-280096

P49841

O15516

1

phosphorylation

down-regulates quantity by destabilization

0.341

We have identified a conserved cluster of serines that include, Ser431, which is a prerequisite phosphorylation site for the generation of BMAL dependent phospho-primed CLOCK and for the potential GSK-3 phosphorylation at Ser427.

SIGNOR-276270

O14965

Q14CS0

2

binding

down-regulates activity

0.304

The UBXN-2/p37/p47 adaptors of CDC-48/p97 regulate mitosis by limiting the centrosomal recruitment of Aurora A.|We found that UBXN-2 and CDC-48 coimmunoprecipitated with AIR-1 from embryonic extracts

SIGNOR-265042

Q8IVP5

Q96HS1

0

dephosphorylation

up-regulates activity

0.627

Here, we identify that the mitochondrially localized PGAM5 phosphatase interacts with and dephosphorylates FUNDC1 at serine 13 (Ser-13) upon hypoxia or carbonylcyanide p-trifluoromethoxyphenylhydrazone (FCCP) treatment. Dephosphorylation of FUNDC1 catalyzed by PGAM5 enhances its interaction with LC3, which is abrogated following knockdown of PGAM5 or the introduction of a cell-permeable unphosphorylated peptide encompassing the Ser-13 and LIR of FUNDC1. We further observed that CK2 phosphorylates FUNDC1 to reverse the effect of PGAM5 in mitophagy activation.

SIGNOR-273654

Q9H0Z9

P49841

0

phosphorylation

down-regulates

0.2

Here, we showed that rnpc1 is phosphorylated at ser195 by glycogen synthase kinase 3 (gsk3). We also provided evidence that ser195 phosphorylation converts rnpc1 from a repressor to an activator of p53.

SIGNOR-203011

O95166

Q9NT62

2

binding

up-regulates activity

0.847

Three human atg8 (hatg8) homologs, lc3, gabarap, and gate-16, have been characterized as modifiers in reactions mediated by hatg7 (an e1-like enzyme) and hatg3 (an e2-like enzyme)

SIGNOR-141868

P04049

Q8IVT5

2

binding

up-regulates activity

0.654

In mammals, RAF family kinases include three catalytically competent enzymes (ARAF, BRAF and CRAF) and two pseudokinases (KSR1 and KSR2) that have been described as scaffolds owing to their apparent ability to bridge RAF isoforms and their substrate, mitogen-activated protein kinase kinase (MEK).Kinase suppressor of Ras (KSR) pseudokinases were also shown to dimerize with kinase-competent RAFs to stimulate catalysis allosterically.

SIGNOR-273880

Q14247

P12931

0

phosphorylation

down-regulates activity

0.801

Erk phosphorylation and a mimicking S405,418D double mutation enhanced cortactin binding and activation of N-WASP. In contrast, Src phosphorylation inhibited the ability of cortactin previously phosphorylated by Erk, and that of S405,418D double mutant cortactin, to bind and activate N-WASP. Furthermore, Y-->D mutation of three tyrosine residues targeted by Src (Y421, Y466, and Y482) inhibited the ability of S405,418D cortactin to activate N-WASP.

SIGNOR-246513

P12757

Q99717

2

binding

down-regulates

0.448

Ski also represses bmp signaling through interactions with smad4 and bmp-specific r-smads, smad1 or smad8.

SIGNOR-95474

Q13467

O75197

2

binding

up-regulates activity

0.67

Here we report that Wnt receptor Frizzled (Frz) and theco-receptors LRP5 and LRP6 (LRP5/6) directly interact with each other and this interaction is regulated by the LRP6 ectodomain.

SIGNOR-258969

Q13133

Q9C0F0

2

binding

down-regulates activity

0.2

We determined that ASXL3 depletion augments the ligand-induced transcriptional activities of LXRα and TRβ, which were repressed by ASXL3 overexpression. The ligand-dependent interactions of ASXL3 with LXRα and TRβ were demonstrated by the GST pull-down and immunoprecipitation analyses. We confirmed that ASXL3 suppresses the expression of LXRα target genes through its recruitment to the LXR-response elements.

SIGNOR-266765

P08670

Q96GD4

0

phosphorylation

down-regulates

0.423

By identifying eight aurora-b phosphorylation sites on vimentin in vitro, we have demonstrated that vimentin-ser-72 is an in vitrophosphorylation site of aurora-b. in vitro analyses revealed that aurora-b phosphorylates vimentin at approximately 2 mol phosphate/mol of substrate for 30 min and that this phosphorylation dramatically inhibits vimentin filament formation.

SIGNOR-96057

Q99683

O95382

2

binding

up-regulates quantity by stabilization

0.551

C-terminal region of ASK1 binds to ASK2 and inhibits the degradation of ASK2

SIGNOR-260831

O14519

P24941

2

binding

down-regulates activity

0.441

The ubiquitously expressed CDK2AP1 protein is the only known specific inhibitor of CDK2, making it an important component of cell cycle regulation during G1-to-S phase transition.

SIGNOR-264781

O95863

P31947

0

relocalization

down-regulates

0.2

Pkd1 phosphorylates ser(11) (s11) on transcription factor snail, a master emt regulator and repressor of e-cadherin expression, triggering nuclear export of snail via 14-3-3_ binding

SIGNOR-168540

P62714

Q9UIC8

0

methylation

up-regulates activity

0.661

Methylation of the carboxy-terminal Leu309 in a conserved TPDYFL309 motif of the C subunit has been shown to enhance the affinity of the PP2A core enzyme for some, but not all, regulatory subunits |The PP2A core enzyme was methylated by a PP2A-specific leucine carboxyl methyltransferase (LCMT1)

SIGNOR-265751

Q8WWM9

Q13309

2

binding

down-regulates quantity by destabilization

0.2

Skp2 induces ubiquitin-dependent degradation of Cygb. To this end, we performed an in vivo ubiquitination assay in HEK293T cells by transfecting relevant plasmids as indicated. The V5-Skp2DN was generated by deleting the N-terminal residues from 1 to 153 containing the F-box domain, which is involved in recruiting Skp2 to the SCF complex.

SIGNOR-272792

P59768

P19174

2

binding

up-regulates

0.2

Furthermore, this work suggested that the gbetagamma subunits released upon gi activation activated phospholipase c-gamma (plc-gamma) to produce inositol 3 phosphate (ip3) which would subsequently increase intracellular ca2+ abundance.

SIGNOR-199138

P28336

O95837

2

binding

up-regulates activity

0.435

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-257422

Q13233

O95819

0

phosphorylation

up-regulates

0.558

Hpk1 binds and phosphorylates mekk1 directly

SIGNOR-44040

P48058

Q9UQM7

0

phosphorylation

up-regulates

0.592

Receptor internalization, altered;intracellular localization

SIGNOR-97546

Q49MG5

P53350

0

phosphorylation

up-regulates

0.275

We also demonstrate that asap is a novel substrate of plk1 phosphorylation and have identified serine 289 as the major phosphorylation site by plk1 in vivo. Asap phosphorylated on serine 289 is localized to centrosomes during mitosis, but this phosphorylation is not required for its plk1-dependent localization at the spindle poles. We show that phosphorylated asap on serine 289 contributes to spindle pole stability in a microtubule-dependent manner

SIGNOR-166564

Q13131

Q16576

1

phosphorylation

up-regulates activity

0.2

AMPK increased HAT1 activity through phosphorylation of HAT1-Ser190 and RBBP7-Ser314| interaction between RBBP7 and HAT1 is required for acetyltransferase activity

SIGNOR-264784

Q13285

P50613

0

phosphorylation

up-regulates

0.366

In conclusion, our results indicate that cdk7, as part of the cak complex and tfiih, phosphorylates sf1 at s203 followed by increased transcriptional activity of sf1

SIGNOR-157952

Q8WUP2

Q9BQL6

2

binding

up-regulates activity

0.448

Kindlin binds migfilin tandem LIM domains and regulates migfilin focal adhesion localization and recruitment dynamics. Two integrin-binding proteins present in FAs, kindlin-1 and kindlin-2, are important for integrin activation, FA formation, and signaling. By binding filamin, migfilin provides a link between kindlin and the actin cytoskeleton.

SIGNOR-266103

Q03113

Q9GZQ4

2

binding

up-regulates activity

0.25

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

SIGNOR-257402

Q03164

Q13535

0

phosphorylation

up-regulates

0.281

Mll is phosphorylated at serine 516 by atr in response to genotoxic stress in the s phase, which disrupts its interaction with, and hence its degradation by, the scf(skp2) e3 ligase, leading to its accumulation.

SIGNOR-25151

P52657

Q06330

2

binding

up-regulates

0.2

Rbp interacts with two transcriptional coactivators: dtafii110, a subunit of tfiid, and tfiia to repress transcription. The domain of dtafii110 targeted by rbp is the same domain that interacts with tfiia

SIGNOR-57832

O60890

P20393

2

binding

up-regulates activity

0.2

Rev-erbα regulates OPHN-1-mediated RhoA/ERM signalling in platelets., The results of the co-immunoprecipitation revealed that Rev-erbα coimmunoprecipitated with OPHN-1 in both mouse and human platelets and this interaction significantly increased upon stimulation with agonist U46619.

SIGNOR-268428

P17252

Q15080

1

phosphorylation

up-regulates activity

0.2

In murine and guinea pig neutrophils, PKCδ is required for the phosphorylation of p40phox, a subunit of the NADPH oxidase complex (Li et al., 2016; Someya et al., 1999). In particular, it mediates phosphorylation of the threonine 154 (T154) residue of p40phox, a key regulatory step in the activation of the NADPH oxidase complex in peripheral neutrophils and B cells, in both mice and humans. In conclusion, the EBV-B cells of patients with PKCδ deficiency have impaired ROS production, associated with lower levels of phosphorylation of the cytosolic NADPH oxidase subunit p40phox by PKCδ.

SIGNOR-277628

Q99835

P23771

1

null

up-regulates activity

0.2

That GATA is a downstream effector of the hedgehog pathway.

SIGNOR-253527

P04141

Q99062

2

binding

up-regulates

0.591

A g-csfr expression plasmid was introduced into interleukin-3 (il-3)-dependent mouse myeloid precursor fdc-p1 cells that normally do not respond to g-csf. G-csf stimulated proliferation of the transformants these results suggested that the g-csfr, but not the il-3/gm-csf receptors, transduced the neutrophilic differentiation signal into cells.

SIGNOR-31963

Q13976

P19429

1

phosphorylation

up-regulates activity

0.357

Phosphorylation at ser 23/24 (e.g., by pka or pkg) results in reduction in myofilament ca2+ sensitivity and an increase in crossbridge cycling rate, leading to acceleration of relaxation and an increase in power output but a reduced economy of contraction. Conversely, phosphorylation at ser 43/45 (by pkc) is associated with reduced maximum ca2+-activated force and decreased crossbridge cycling rates, which are likely to reduce power output and delay relaxation, with an increased economy of contraction.

SIGNOR-134644

P12814

P18031

0

dephosphorylation

up-regulates

0.335

Here we report that protein-tyrosine phosphatase 1b (ptp 1b) is an ?-Actinin phosphatase.

SIGNOR-141634

P19086

O43614

2

binding

up-regulates activity

0.25

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

SIGNOR-257124

O95477

P00533

0

phosphorylation

down-regulates quantity by destabilization

0.295

We further provide in vitro evidence that epidermal growth factor receptor (EGFR)-mediated phosphorylation regulated ABCA1 ubiquitination |The EGFR selective inhibitor PD168393 blocked the EGFR-ABCA1 interaction and abolished ABCA1Ser2054 phosphorylation|

SIGNOR-264419

P35499

Q96PU5

0

ubiquitination

down-regulates quantity by destabilization

0.279

The control of Nav density at the cell membrane is crucial to ensuring normal neuronal excitability. Navs are subject to posttranslational modifications that may influence their cell membrane availability. Ubiquitylation is a key process that orchestrates the internalization and subsequent degradation or recycling of Navs. This is accomplished by ubiquitin protein ligases, such as NEDD4-2 (neuronal precursor cell expressed developmentally downregulated-4 type 2).

SIGNOR-253460

O43318

O00743

0

dephosphorylation

down-regulates activity

0.372

Protein phosphatase 6 down-regulates TAK1 kinase activation in the IL-1 signaling pathway|From proteomic analysis of TAK1-binding proteins, we identified protein phosphatase 6 (PP6), a type-2A phosphatase, and demonstrated that PP6 associated with and inactivated TAK1 by dephosphorylation of Thr-187.

SIGNOR-248292

P06241

Q05655

1

phosphorylation

up-regulates activity

0.597

In conclusion, our in vitro data and previous report ( xref ) demonstrate that Fyn phosphorylation of Y311 on PKC\u03b4 activates the apoptotic signaling cascade in DAergic neurons in response to neurotoxic insults.

SIGNOR-279737

O00743

Q8N884

1

dephosphorylation

down-regulates activity

0.2

In this study, we found that PPP6C suppressed phosphorylation of human cGAS (hcGAS) at S435 or mouse cGAS (mcGAS) at S420 in its substrate-binding pocket, thus preventing its binding to GTP and inhibiting the synthesis of cGAMP.|These data suggest that PPP6C inhibits cGAS activity.

SIGNOR-276990

Q9HAU4

O95630

1

polyubiquitination

down-regulates quantity by destabilization

0.529

RNF11 recruits AMSH to Smurf2 E3 ligase. Smurf2 promotes ubiquitination of AMSH in the presence of wt RNF11. Previously, we have shown that RNF11 interacts with the HECT-type E3 ligases AIP4 and Smurf2. Here, we show that RNF11 binds to AMSH in mammalian cells and that this interaction is independent of the RNF11 RING-finger domain and the PY motif. Our results also demonstrate that AMSH is ubiquitinated by Smurf2 E3 ligase in the presence of RNF11 and that a consequent reduction in its steady-state level requires both RNF11 and Smurf2. RNF11 therefore recruits AMSH to Smurf2 for ubiquitination, leading to its degradation by the 26S proteasome.

SIGNOR-272951

Q02156

Q16612

1

phosphorylation

down-regulates quantity by destabilization

0.2

Site-directed mutagenesis of S59A retarded P311 degradation and induced glioma cell motility. In contrast, S59D mutation resulted in the rapid degradation of P311 and reduced glioma cell migration.Taken together, our results show that the serine phosphorylation of P311 is dependent on the function of both PKCε and PKCz.

SIGNOR-273830

P16885

Q92835

0

dephosphorylation

down-regulates activity

0.312

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-268455

P21796

Q5TGU0

2

binding

up-regulates activity

0.309

Our results demonstrate the existence of a VDAC-TSPO2-ANT complex that mediates ATP release from RBCs. We previously demonstrated that the translocase protein TSPO2 together with the voltage-dependent anion channel (VDAC) and adenine nucleotide transporter (ANT) were involved in a membrane transport complex in human red blood cells (RBCs). . The present results show that TSPO ligands induce polymerization of VDAC, coupled to activation of ATP release by a supramolecular complex involving VDAC, TSPO2 and ANT.

SIGNOR-261826

Q9UM73

Q14469

1

phosphorylation

up-regulates activity

0.266

NPM-ALK also directly phosphorylates HES1 protein.

SIGNOR-280181

O14920

P35568

1

phosphorylation

down-regulates activity

0.654

IRS-1 is a novel direct substrate for IKK and that phosphorylation of IRS-1 at Ser(312) (and other sites) by IKK may contribute to the insulin resistance mediated by activation of inflammatory pathways.

SIGNOR-251297

Q15233

P11387

2

binding

up-regulates

0.373

We show that the psf/p54 dimer has pronounced stimulatory effect on dna catalysis by topoisomerase i

SIGNOR-60557

Q00535

P30086

1

phosphorylation

down-regulates quantity by destabilization

0.337

Here, we demonstrate that RKIP is a substrate of cyclin-dependent kinase 5 (CDK5) in neurons and that the phosphorylation of RKIP at T42 causes the release of Raf-1. Moreover, T42 phosphorylation promotes the exposure and recognition of the target motif "KLYEQ" in the C-terminus of RKIP by chaperone Hsc70 and the subsequent degradation of RKIP via chaperone-mediated autophagy (CMA).

SIGNOR-276672

Q14258

Q15911

1

polyubiquitination

down-regulates quantity by destabilization

0.451

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

SIGNOR-272048

O14939

P52333

0

phosphorylation

up-regulates

0.407

We identified three kinases capable of phosphorylating pld2 in vitro-epidermal growth factor receptor (egfr), jak3, and src (with jak3 reported for the first time in this study)-that phosphorylate an inhibitory, an activator, and an ambivalent (one that can yield either effect) site, respectively. Mass spectrometry analyses indicated the target of each of these kinases as y(296) for egfr, y(415) for jak3, and y(511) for src.

SIGNOR-163858

O75381

Q92968

2

binding

up-regulates activity

0.92

Pex14 interacts via its proline-rich motif with the SH3 domain of Pex13. We conclude that the association of Pex13 with Pex14 is an essential step in peroxisomal protein import

SIGNOR-253029

Q8IZP0

P22681

2

binding

up-regulates

0.371

Here we uncover a novel interaction between abi-1 and the cbl ubiquitin ligase and show that abi-1 mediates cbl accumulation to the plasma membrane upon stimulation by egf.

SIGNOR-154162

O15068

P60953

1

guanine nucleotide exchange factor

up-regulates activity

0.751

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-260560

Q96SN8

Q13257

1

transcriptional regulation

up-regulates quantity by expression

0.309

These data indicate that CDK5RAP2 is a positive regulator of both the BUBR1 promoter and the MAD2 promoter

SIGNOR-260313

P38435

O43852

2

binding

down-regulates activity

0.401

Results are presented that demonstrate that the endoplasmic reticulum chaperone protein calumenin is associated with gamma-carboxylase and inhibits its activity.

SIGNOR-265910

P17612

P17655

1

phosphorylation

down-regulates

0.262

Activation of m-calpain (calpain ii) by epidermal growth factor is limited by protein kinase a phosphorylation of m-calpain.These Data point to a novel mechanism of negative control of calpain activation, direct phosphorylation by pka.

SIGNOR-116248

O00273

O76075

2

binding

down-regulates

0.929

Dff is a heterodimer of 40 kda and 45 kda subunits.

SIGNOR-29729

Q9UNH5

P30291

1

dephosphorylation

up-regulates quantity by stabilization

0.545

In particular, we found that Cdc14A inhibits Wee1 degradation through the dephosphorylation of Ser-123 and Ser-139 residues.

SIGNOR-267470

O96017

P30307

1

phosphorylation

down-regulates activity

0.856

Activated chk2 in turn phosphorylates cdc25c at serine-216 contributing to the g2/m checkpoints. Cds1 phosphorylates and inactivates cdc25 in vitro|CDC25C is phosphorylated on Ser 216 throughout interphase, but not in mitosis. This creates a binding site for 14‐3‐3 proteins | It has been suggested that 14‐3‐3 protein binding is responsible for retaining Cdc25C in the cytoplasm during interphase, thereby contributing to the prevention of premature initiation of mitotic events

SIGNOR-102779

Q9Y4C4

O43164

0

ubiquitination

up-regulates activity

0.403

These results suggest that the ubiquitylation of MFHAS1 by praja2 has a vital role in M1 macrophage polarization and promotes the transformation of M2 macrophages to M1 macrophages through both the JNK and p38 pathways.

SIGNOR-278559

Q16584

P24941

0

phosphorylation

up-regulates activity

0.2

Using in vitro kinase assays and phosphomutants, we determined that CDK1 phosphorylates MLK3 on Ser548 and decreases MLK3 activity during mitosis, whereas CDK2 phosphorylates MLK3 on Ser770 and increases MLK3 activity during G1/S and G2 phases.

SIGNOR-277604

Q92547

O60671

2

binding

up-regulates

0.619

The 9-1-1 complex functions as a clamp, encircling the dna, and recruits the brct domain-containing protein topbp1 in a phospho-dependent manner

SIGNOR-179379

Q13418

P49841

1

phosphorylation

down-regulates activity

0.69

ILK can also directly phosphorylates GSK-3\u03b2 at Ser 9, inactivate it, and lead to activation of some transcription factors [ ].|ILK knockdown activates GSK-3beta.

SIGNOR-278252

P68400

P28482

0

phosphorylation

up-regulates

0.369

Erk2, which is activated by egfr signaling, directly binds to ck2alpha via the erk2 docking groove and phosphorylates ck2alpha primarily at t360/s362, subsequently enhancing ck2alpha activity

SIGNOR-161855

P27361

P49418

1

phosphorylation

down-regulates activity

0.274

Thus, we propose that mapk phosphorylation of amphiphysin1 controls ngf receptor/trka-mediated endocytosis by terminating the amphiphysin1-ap-2 interaction.Our results indicate that phosphorylation of amphiphysin 1 at ser-285 and/or ser-293 affects the function of amphiphysin1.Mapk phosphorylation of ser-285 and ser-293 could modulate the interaction between prd and ap-2, resulting in the dissociation of amphiphysin1 from ap-2.

SIGNOR-126867

Q9H4B4

P11388

1

phosphorylation

up-regulates

0.268

The direct phosphorylation of thr(1342) of topoisomerase iialpha by plk3 was demonstrated with an in vitro kinase assay, and overexpression of plk3 induced the phosphorylation of thr(1342) in cellular topoisomerase iialpha. it is possible that plk3 regulates the activity of topoisomerase iia by phosphorylation in a cell-cycle dependent manner. Another possibility is that plk3 regulates the activity of topoisomerase iia when the checkpoint is activated.

SIGNOR-159596

Q05655

P04637

1

phosphorylation

up-regulates

0.677

Here, we show that the pro-apoptotic kinase, protein kinase c delta (pkcdelta), is involved in phosphorylation of p53 on ser(46). pkcdelta potentiates p53-dependent apoptosis by ser(46) phosphorylation in response to genotoxic stress.

SIGNOR-143382

O75506

Q00613

2

binding

down-regulates activity

0.699

HSBP1 is nuclear-localized and interacts in vivo with the active trimeric state of HSF1 that appears during heat shock. During attenuation of HSF1 to the inert monomer, HSBP1 associates with Hsp70. HSBP1 negatively affects HSF1 DNA-binding activity, and overexpression of HSBP1 in mammalian cells represses the transactivation activity of HSF1. HSF1 interacts with HSBP1 in vivo and is a nuclear localized protein.

SIGNOR-261181

P50052

P50148

2

binding

up-regulates

0.504

These neuropeptide gpcrs are coupled to the activation of phospholipase c, and therefore to calcium ele- vation and protein kinase c (pkc) activation, through g proteins of the alfaq family

SIGNOR-106995

P14921

Q99684

2

binding

down-regulates activity

0.426

Co-immunoprecipitation analyses and glutathione-S-transferase pull-down assays revealed that ETS1 bound directly to GFI1 via its Ets domain, and GFI1 bound to ETS1 via its zinc-finger domain. Luciferase (Luc) assays using artificial reporters showed that GFI1 repressed ETS1-mediated transcriptional activation and ETS1 repressed GFI1-mediated transcriptional activation, in a dose-dependent manner.

SIGNOR-254202

P04629

A7KAX9

1

relocalization

up-regulates

0.602

Grit translocation was regulated by receptor stimulation

SIGNOR-95809

Q16539

P35236

2

phosphorylation

down-regulates activity

0.59

The noncatalytic N terminus of HePTP binds Erk and p38 and is phosphorylated at Ser-72 and Thr-45 by these kinases. the N terminus of HePTP binds Erk and p38 but may release them upon phosphorylation.it is clear that phosphorylation of HePTP at Thr-45 and/or Ser-72 is not required for inhibition of MAP kinase. Rather, it seems that phosphorylation has the opposite effect, namely to lessen the inhibitory effect of HePTP.

SIGNOR-250109

Q9Y613

P60709

2

binding

up-regulates quantity by stabilization

0.344

Fhos, a mammalian formin, directly binds to F-actin via a region N-terminal to the FH1 domain and forms a homotypic complex via the FH2 domain to promote actin fiber formation

SIGNOR-276613

Q92558

O43295

2

binding

up-regulates

0.553

Wrp binds directly to wave-1 through its src homology domain 3 and specifically inhibits rac function in vivo.

SIGNOR-95967

Q93097

Q9NPG1

2

binding

up-regulates

0.63

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-131777

P20393

Q9UBK2

0

transcriptional regulation

up-regulates quantity by expression

0.522

Transcriptional coactivator PGC-1α integrates the mammalian clock and energy metabolism. Here we show that PGC-1alpha (Ppargc1a), a transcriptional coactivator that regulates energy metabolism, is rhythmically expressed in the liver and skeletal muscle of mice. PGC-1alpha stimulates the expression of clock genes, notably Bmal1 (Arntl) and Rev-erbalpha (Nr1d1), through coactivation of the ROR family of orphan nuclear receptors. Chromatin immunoprecipitation (ChIP) assays in HepG2 cells indicate that PGC-1α is present near RORE on the proximal Bmal1 promoter.These results indicate that PGC-1α activates Bmal1 transcription by altering the local chromatin environment from a repressive to an active state.

SIGNOR-268030

Q8IVM0

P06239

0

phosphorylation

down-regulates activity

0.2

We found that Ymer was considerably phosphorylated on tyrosine residues also via Src family kinases such as Lck. A luciferase reporter assay showed that mutation of tyrosines on Ymer (YmerY217/279/304F) results in loss of the inhibitory activity for NF-kappaB signaling.

SIGNOR-262855

Q04759

Q9BWT7

0

relocalization

up-regulates activity

0.435

TBKBP1 recruits TBK1 to protein kinase C-theta (PKCθ) through a scaffold protein, CARD10. This enables PKCθ to phosphorylate TBK1 at Ser 716, a crucial step for TBK1 activation

SIGNOR-272471

O14920

Q9Y6K9

2

phosphorylation

down-regulates activity

0.962

In this study we analyze the ikkbeta-mediated phosphorylation of the ikk-binding domain of nemo. In vitro, ikkbeta phosphorylates three serine residues in the domain of nemo at positions 43, 68, and 85. However, mutational analysis revealed that only the phosphorylation of serine 68 in the center of the ikk-binding domain plays an essential role for the formation and the function of the ikk complex. Thus, ser(68) phosphorylation attenuates the amino-terminal dimerization of nemo as well as the ikkbeta-nemo interaction. I

SIGNOR-158659

Q92949

Q9UI46

1

transcriptional regulation

up-regulates quantity by expression

0.368

FOXJ1 expression in basal cells induced the expression of a panel of cilia-associated genes, including centrin 2 (CETN2); dynein, axonemal, heavy chain 11 (DNAH11); dynein, axonemal, intermediate chain 1 (DNAI1); dynein, axonemal, light intermediate chain 1 (DNALI1); EF-hand domain, C-terminal, containing 1 (EFHC1); sperm associated antigen 6 (SPAG6); tektin 1 (TEKT1), TEKT2 and tubulin, alpha 1a (TUBA1A; Figure 3C and Additional file 2: Table S1).

SIGNOR-266932

P98164

P16035

2

binding

up-regulates quantity

0.2

We show that megalin/LRP-2 acts as an endocytic receptor for proMMP-2:TIMP-2 complex. We found that RAP, an antagonist of the LDL receptor family18, competed with binding of proMMP-2:TIMP-2 complex onto rat BN16 epithelial cells.

SIGNOR-265254

O60936

P19784

0

phosphorylation

up-regulates activity

0.2

Phosphorylation of ARC at T149 Is Required for Its Antiapoptotic Effect. Here we report that the function of ARC is regulated by protein kinase CK2. ARC at threonine 149 is phosphorylated by CK2. This phosphorylation targets ARC to mitochondria. ARC is able to bind to caspase-8 only when it is localized to mitochondria but not to the cytoplasm.

SIGNOR-262836

Q92831

P15172

2

binding

up-regulates

0.647

Our results provide direct evidence that myod acetylation functionally activates the protein and show that both pcaf and cbp/p300 are candidate enzymes for myod acetylation in vivo

SIGNOR-81059

Q02156

O14649

1

phosphorylation

down-regulates activity

0.2

We have previously shown that carbamylated PAF-induced repolarization abnormalities result from the protein kinase C (PKC) ε-dependent phosphorylation of the two-pore domain potassium channel TASK-1. Further studies identified threonine 383 in the C terminus of human and canine TASK-1 as the phosphorylation site required for PAF-dependent inhibition of the channel.

SIGNOR-276431

P49759

Q07955

1

phosphorylation

up-regulates activity

0.673

In a previous study, we showed that CLK1 phosphorylates SRSF1 to a greater extent than SRPK1, inducing a hyper-phosphorylated state that can be readily detected by a gel shift on SDS-PAGE. xref In xref , the phosphorylation of SRSF1 in single turnover experiments using SRPK1 and CLK1 is shown.|Unlike SRPK1, CLK1 induces a unique structural form of SRSF1 observed by SDS-PAGE that is exclusively the result of Ser-Pro rather than Arg-Ser phosphorylation.

SIGNOR-279608

P27361

P51170

1

phosphorylation

down-regulates quantity by destabilization

0.28

Using a number of different approaches it was demonstrated that the protein kinase acting on betaThr-613 and gammaThr-623 is the extracellular regulated kinase (ERK). It is suggested that an ERK-mediated phosphorylation of betaThr-613 and gammaThr-623 down-regulates the channel by facilitating its interaction with Nedd4.

SIGNOR-249449

P55211

Q5T447

0

polyubiquitination

down-regulates activity

0.2

HECTD3 binds and ubiquitinates caspase-9.HECTD3 inhibits caspase-9 oligomerization and association with Apaf-1. HECTD3 suppressing caspase-9 activation is dependent on T157 phosphorylation by ERK.

SIGNOR-272329

P09471

P30411

2

binding

up-regulates activity

0.2

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

SIGNOR-256974

Q9UBF6

Q13616

2

binding

up-regulates activity

0.857

SAG was found to be the second family member of Rbx (RING box protein) or ROC (Regulator of cullins) or Hrt that is a component of SCF E3 ubiquitin ligase. Indeed, like ROC1/Rbx1/Hrt1, SAG binds to Cul1 and SAG-Cul1 complex has ubiquitin ligase activity to promote poly-ubiquitination of E2/Cdc34.

SIGNOR-271444

Q9UQB8

P63000

2

binding

up-regulates

0.739

Here we demonstrate that irsp53, a substrate for insulin receptor with unknown function, is the 'missing link' between rac and wave. Activated rac binds to the amino terminus of irsp53, and carboxy-terminal src-homology-3 domain of irsp53 binds to wave to form a trimolecular complex.

SIGNOR-85302

Q9H3D4

O94901

1

transcriptional regulation

up-regulates quantity by expression

0.2

Here we show that in the developing skin, epidermal progenitor cells of mice lacking p63 transcription factor display alterations in the nuclear shape accompanied by a marked decrease in expression of several nuclear envelope-associated components (Lamin B1, Lamin A/C, Sun1, Nesprin-3, Plectin) compared with controls. Furthermore, chromatin immunoprecipitation-quantitative PCR assay showed enrichment of p63 on Sun1, Syne3, and Plec promoters, suggesting them as p63 targets.

SIGNOR-263278

Q99626

Q12864

1

transcriptional regulation

up-regulates quantity by expression

0.406

The present study aims to identify the transcription factors which interact and regulate CDH17 promoter activity that might contribute to the up-regulation of CDH17 gene in human HCC|we identified hepatic nuclear factor 1α (HNF1α) and caudal-related homeobox 2 (CDX2) binding sites at the proximal promoter region which modulate the CDH17 promoter activities in two HCC cell lines (Hep3B and MHCC97L)

SIGNOR-253963

P00519

Q8TDZ2

1

phosphorylation

up-regulates activity

0.312

Biochemical assays revealed Abl phosphorylates Mical to directly amplify Mical Redox-mediated F-actin disassembly.|We now find that the Abl non receptor protein tyrosine kinase and oncoprotein signaling pathway activates Mical to direct multiple cellular effects - including extending and shaping cellular processes, guiding axons, and orchestrating cancer cell invasion, colony formation, and survival.

SIGNOR-279674

P40198

Q12913

0

dephosphorylation

down-regulates activity

0.387

We also determined that recombinant PTPRJ directly dephosphorylates the cytoplasmic tyrosine residues of purified full-length CEACAM3 and recognizes synthetic CEACAM3-derived phospho-peptides as substrates.|We show depletion of PTPRJ results in a gain-of-function phenotype, while overexpression of a constitutively active PTPRJ phosphatase strongly reduces bacterial uptake via CEACAM3.

SIGNOR-277091

P56278

Q9Y243

2

binding

up-regulates

0.364

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

SIGNOR-81677

P68366

Q5SQI0

0

acetylation

up-regulates quantity by stabilization

0.262

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

SIGNOR-272249

P15289

P69905

1

acetylation

up-regulates activity

0.2

ASA acetylates hemoglobin. Purified acetylated hemoglobin had a slightly increased oxygen affinity and decreased heme-heme interaction.

SIGNOR-251773

Q05513

P09211

1

phosphorylation

up-regulates activity

0.2

Peptide phosphorylation analyses and both phosphorylation and enzyme kinetic studies with GSTP1 proteins mutated at candidate amino acid residues established Ser-42 and Ser-184 as putative phospho-acceptor residues for both kinases in the GSTP1 protein. Together, these findings show PKA- and PKC-dependent phosphorylation as a significant post-translational mechanism of regulation of GSTP1 function. Together, these results further support S42 and S184 as major phosphor-acceptor residues for PKA and PKC and suggest that the increased activity of the phospho-GSTP1 was not simply a consequence of the negative charge introduced in the GSTP1 protein by the phosphate group.All eight PKC isoforms, PKC-α, PKC-βI, PKC-βII, PKC-ε, PKC-γ, PKC-η, and PKC-ζ phosphorylated the GSTP1 protein efficiently

SIGNOR-276017