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
P45983	P05067	1	phosphorylation	up-regulates	0.71	Phosphorylation of amyloid precursor protein at threonine 668 is essential for its copper-responsive trafficking in sh-sy5y neuroblastoma cells. We found that the threonine 668 within the abetapp intracellular domain (aid or elsewhere aicd) is indeed phosphorylated by jnk1	SIGNOR-117852
P41221	Q8NBF1	0	transcriptional regulation	up-regulates quantity by expression	0.248	GLIS1, a novel hypoxia-inducible transcription factor, promotes breast cancer cell motility via activation of WNT5A	SIGNOR-269040
Q9H4E7	P60953	1	guanine nucleotide exchange factor	up-regulates activity	0.392	Furthermore, membrane targeting of the SLAT Dbl-homology (catalytic) domain was sufficient to trigger TCR-mediated NFAT activation and Th1 and Th2 differentiation in a Cdc42-dependent manner.	SIGNOR-253369
O60928	P17252	0	phosphorylation	down-regulates	0.2	After pharmacological pkc activation, kir7.1 currents were strongly inhibited. Co-application of pkc inhibitors attenuated this effect. Inactivation of pkc consensus sites also strongly attenuated the effect with a single site ((201)s) being essential for almost the total pkc sensitivity.	SIGNOR-181863
Q07912	P09619	0	phosphorylation	up-regulates activity	0.359	Mutational analysis suggested that Y635 of ACK1 is a PDGFR-β phosphorylation site and that the ACK1 Y635F mutant abrogated the sequential activation of AKT.	SIGNOR-276854
O60610	P06493	0	phosphorylation	down-regulates activity	0.2	In this study, we found that Cdk1 phosphorylated DIAPH1, which inhibited the interaction between DIAPH1 and profilin1 (PFN1) during metaphase.\|Thus, the results suggest that the level of cortical F-actin has to be finely maintained by Cdk1 mediated positive and negative regulation of DIAPH1.	SIGNOR-279598
P12931	Q01973	0	phosphorylation	up-regulates	0.318	Ror1 binds to and phosphorylates c-src / ror1 kinase-dependent c-src activation	SIGNOR-196751
P52333	P52333	2	phosphorylation	up-regulates	0.2	The phosphorylation of wt jak3 and y980f/y981f/y785f mutant jak3 is presumably mediated through autophosphorylation at distinct jak3 sites within this model systemhosphorylation of jak3 on y785 has been reported to create a binding site for the adaptor protein sh2b-beta	SIGNOR-160660
Q9UNS2	Q07889	2	binding	up-regulates quantity by stabilization	0.2	Our observations characterizing the interaction between CSN3 and the Sos1 HD suggest that this domain not only functions regulating Sos-GEF autoinhibition but is also involved in other functional roles, such as the control of Sos protein stability and homeostasis by modulating the degradation and intracellular levels of Sos1.	SIGNOR-256217
P61586	Q3KR16	0	guanine nucleotide exchange factor	up-regulates activity	0.583	We therefore developed a screening-compatible live-cell imaging assay, using FRET-based biosensors for the prototype GTPases RHOA, RAC1 and CDC4215,19,20 (Extended Data Fig. 2 and Supplementary Note 1)\|We found catalytic activities for 45/75 RhoGEFs and 48/63 RhoGAPs\| Our data thus not only reveal extensive promiscuity among regulators, but also that the inactivating RhoGAPs are less selective than the activating RhoGEFs (p-value=0.02)(Supplementary Table 2).	SIGNOR-260567
Q8TBJ4	Q0VAM2	2	binding	up-regulates activity	0.2	Oncogenic effects of imbalanced PRG3 are mediated via PRG3-RasGEF1 interaction and Ras activation. PRG3 interacts with RasGEF1 in vivo.We could further show that PRG3 executes the binding to RasGEF1 predominantly via its C-terminal domain (CT) and in the consequence causes Ras activation.	SIGNOR-261806
Q8NBP7	Q8IXL6	0	phosphorylation	up-regulates activity	0.537	Herein, we report that Fam20C and Fam20A significantly eliminate the Furin-cleavage of PCSK9 (XREF_FIG, lanes 5, 6), thereby enhancing the pPCSK9 activity\|Herein, we show that Fam20C phosphorylates PCSK9 at Serines 47, 666, 668 and 688.	SIGNOR-278935
Q969F8	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-256893
P63096	P60953	2	binding	up-regulates activity	0.523	These findings indicate that both G alpha(i) and G beta gamma stimulate Rac and Cdc42 pathways with lysophosphatidic acid-induced cell spreading on fibronectin	SIGNOR-256531
Q92934	P17252	0	phosphorylation	down-regulates activity	0.2	Phosphorylation of BAD at ser112 and ser136 in the setting of lapatinib treatment was fully restored by PRKACA expression in BT474, SKBr3, and ZR-75-30 cells (XREF_FIG).\|We found that neither PRKACA nor PIM1 restored MAPK or PI3K activation after lapatinib or trastuzumab treatment, but rather inactivated the pro apoptotic protein BAD, thereby permitting survival signaling through BCL-XL.	SIGNOR-280080
Q12899	P78549	1	ubiquitination	down-regulates quantity by destabilization	0.263	We also demonstrated that TRIM26 directly polyubiquitylates NTH1 in cells and that TRIM26 targets newly synthesized NTH1 protein for ubiquitylation dependent degradation.	SIGNOR-278733
Q9Y5G1	Q9Y5H9	2	binding	up-regulates activity	0.2	The clustered protocadherins comprise the largest subfamily of the cadherin superfamily and are predominantly expressed in the nervous system. Pcdh-alpha proteins interact with beta1-integrin to promote cell adhesion. They also form oligomers with Pcdh-gamma proteins at the same membrane sites.	SIGNOR-265685
P12931	O15530	1	phosphorylation	up-regulates activity	0.585	Using site-directed mutants, we show that, although phosphorylation on tyr-373/376 is important for pdk1 activity, phosphorylation on tyr-9 has no effect on the activity of the kinase. Both of these residues can be phosphorylated by v-src tyrosine kinase in vitro, and co-expression of v-src leads to tyrosine phosphorylation and activation of pdk1.	SIGNOR-109533
O15013	P60953	1	guanine nucleotide exchange factor	up-regulates activity	0.499	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-260537
P15173	P38936	1	transcriptional regulation	down-regulates quantity by repression	0.331	P21 is regulated by MyoD and myogenin in normal muscle cells and the inactivation of these factors in RMS cells contributes to the silencing of p21 in RMS cells	SIGNOR-251575
Q9NPG1	O00755	2	binding	up-regulates activity	0.646	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-131897
P63096	O14939	2	binding	down-regulates	0.307	The results of this study suggest that membrane phospholipase d activity can be negatively regulated via gi	SIGNOR-48256
O43524	P45983	0	phosphorylation	up-regulates activity	0.65	As JNK1 phosphorylates FOXO3 at S574, 12 allowing formation of the proapoptotic species, we tested whether FOXO3 acetylation is required for the JNK1-FOXO3 interaction.	SIGNOR-280030
P31943	P12931	1	post transcriptional regulation	up-regulates quantity by expression	0.291	HnRNP H is a component of a splicing enhancer complex that activates a c-src alternative exon in neuronal cells.	SIGNOR-261273
P30291	Q9UNH5	0	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
O43395	Q13107	0	deubiquitination	down-regulates activity	0.487	Prp3 is deubiquitinated by Usp4 and its substrate targeting factor, the U4/U6 recycling protein Sart3, which likely facilitates ejection of U4 proteins from the spliceosome during maturation of its active site.	SIGNOR-271975
P24928	P50613	0	phosphorylation	down-regulates	0.789	Although there is some inconsistency in the literature, it is generally thought that cdk7, a component of the transcription factor (tf) iih, is a major ser-5 kinase, whereas cdk9, a component of positive transcription elongation factor (p-tef) b, is a major ser-2 kinase within cells. These results suggest that subsequent to h2o2 treatment, the ser-5-phosphorylated form, but not the ser-2-phosphorylated form or the unphosphorylated form, is targeted for rapid proteasomal degradation through its ubiquitination.	SIGNOR-120024
P68431	Q96T68	0	methylation	up-regulates activity	0.2	Here, we have characterized a previously undescribed member of the histone H3K9 methyltransferase family named CLLD8 (or SETDB2 or KMT1F). This protein contributes to the trimethylation of both interspersed repetitive elements and centromere-associated repeats and participates in the recruitment of heterochromatin protein 1 to centromeres. Methylation of histone H3 at lysine 9 (H3K9) has emerged as an important player in the formation of heterochromatin, chromatin condensation, and transcriptional repression.	SIGNOR-263896
P68400	Q13283	1	phosphorylation	down-regulates activity	0.239	We also show that casein kinase 2 phosphorylates G3BP1 at serine 149 in vitro and in cells. These data support a role for casein kinase 2 in regulation of protein synthesis by downregulating stress granule formation through G3BP1.CK2 regulates SG disassembly during stress recovery.G3BP1 is among the strongest SG nucleating proteins, and previous work indicated that G3BP1 phosphorylation at S149 restricts stress granule assembly by partly inhibiting G3BP1 oligomerization	SIGNOR-260748
P60953	Q3KRB8	0	gtpase-activating protein	down-regulates activity	0.49	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-260468
P07947	P09086	1	phosphorylation	up-regulates activity	0.2	These data suggest that Yes1 is the TKI-sensitive kinase that can directly phosphorylate OCT2.	SIGNOR-279664
Q96T51	P20338	2	binding	up-regulates activity	0.68	Here, we have demonstrated that Rab14 interacts with RUFY1, previously identified as a Rab4 effector, and is required for RUFY1 recruitment onto endosomes and efficient recycling of Tfn.\|We also found that enlargement of early endosomes mediated by RUFY1 requires its interaction with Rab4	SIGNOR-261280
P07900	P37173	2	binding	up-regulates	0.384	The data in fig. 5 suggest that hsp90 specifically interacts with t?RI And t?RII In vitro and in vivo. Coupled with our data showing that loss of hsp90 function decreases t?R Levels and blocks tgf?-Induced smad2/3 activation and transcription, this result suggests that hsp90 controls tgf? Signaling as an essential component for stabilizing t?Rs.	SIGNOR-179271
O43255	Q16539	0	phosphorylation	up-regulates	0.2	We show that siah2 is subject to phosphorylation by p38 mapk, which increases siah2-mediated degradation of phd3.	SIGNOR-149890
Q13526	P53350	0	phosphorylation	up-regulates	0.424	Here we demonstrate that ser-65 in pin1 is the major site for plk1-specific phosphorylation, and the polo-box domain of plk1 is required for this phosphorylation. Interestingly, the phosphorylation of pin1 by plk1 does not affect its isomerase activity but rather is linked to its protein stability. pin1 is ubiquitinated in hela s3 cells, and substitution of glu for ser-65 reduces the ubiquitination of pin1.	SIGNOR-139919
P17612	O14649	1	phosphorylation	up-regulates activity	0.2	Mutation of the ser393 to alanine, which can neither be phosphorylated nor mimic a phosphorylated residue, resulted in the channel failing to pass current all of our findings support the conclusion that camp-dependent protein kinase is responsible for the phosphorylation of the terminal serine in both k2p3.1 and k2p9.1.	SIGNOR-172430
P17252	Q15172	1	phosphorylation	down-regulates activity	0.341	In this study, we identified a novel phosphorylation site at Ser(41) of B56α. This phosphoamino acid residue was efficiently phosphorylated in vitro by PKCα.	SIGNOR-276603
Q9NRA0	P27361	0	phosphorylation	up-regulates	0.521	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-153387
O43524	P11309	0	phosphorylation	down-regulates activity	0.387	Pim1s expression induced the phosphorylation of foxo3a (fig. 5a and b) and inactivated its transcriptional activity (fig. 5c). A previous report showed that phosphorylation at t32, s253, and s315 residues in foxo3a induced 14-3-3 binding, nuclear export, and proteasomemediated degradation (42).	SIGNOR-179308
Q96QS3	P17252	0	phosphorylation	up-regulates activity	0.2	We confirm that ARX is phosphorylated by PRKCA and demonstrate phosphorylation at serine 174. We demonstrate that phosphorylation is required for correct transcriptional activity of the ARX protein using transcriptome-wide analysis of gene expression of phospho-null mutants (alanines replacing serines) compared to ARX wild-type (ARX-WT) overexpressed in pancreatic alpha TC cells.	SIGNOR-277418
Q9BYB0	Q9Y2H0	0	relocalization	up-regulates activity	0.2	SHANK proteins are ‘master’ scaffolding proteins that tether and organize intermediate scaffolding proteins. They are located at excitatory synapses, where they are crucial for proper synaptic development and function. SAPAP proteins subsequently bind to the PDZ domain of members of the SHANK protein family. SHANK proteins then bind to the actin cytoskeleton and to Homer protein, which in turn interacts with mGluRs. Through these extended links, PSD95, SAPAP, SHANK and Homer proteins form a quaternary complex that brings together mGluR and NMDAR complexes in the PSD (FIG. 3).	SIGNOR-264597
P49841	Q96RG2	0	phosphorylation	down-regulates activity	0.288	In vitro, PASK directly phosphorylates GSK3\u03b2 on its inactivating phosphorylation site Ser(9).\|We conclude that PASK phosphorylates and inactivates GSK3\u03b2, thereby preventing PDX-1 serine phosphorylation and alleviating GSK3\u03b2-mediated PDX-1 protein degradation in pancreatic \u03b2-cells.	SIGNOR-279639
Q96S59	Q13315	0	phosphorylation	up-regulates activity	0.439	We demonstrate that ATM phosphorylates RanBP9 in response to Ionizing Radiation and mediates its nuclear accumulation.	SIGNOR-279005
P09471	P30550	2	binding	up-regulates activity	0.268	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-257247
Q9Y478	Q13131	0	phosphorylation	up-regulates	0.925	Mutation of serine 108 to alanine, an autophosphorylation site within the glycogen binding domain of the beta1 subunit, almost completely abolishes activation of ampk by a-769662 in cells and in vitro, while only partially reducing activation by amp	SIGNOR-157553
P84243	P41231	0	demethylation	up-regulates activity	0.2	KDM5 subfamily is capable of removing tri‐ and di‐ methyl marks from lysine 4 on histone H3 (H3K4). Depending on the methylation site, its effect on transcription can be either activating or repressing.	SIGNOR-264307
P03372	Q13153	0	phosphorylation	up-regulates	0.534	Pak1 directly phosphorylated the activation function-2 domain of the er at the n-terminal residue ser305, and its mutation to ala (s305a) abolished the pak1-mediated phosphorylation and transactivation functions of the er	SIGNOR-94206
P32004	P17252	0	phosphorylation	down-regulates activity	0.2	CKII phosphorylates T1172 of the L1 CD and phosphorylation of T1172 is responsible for loss of 2C2 signal.	SIGNOR-276283
Q8IUQ4	Q13315	0	phosphorylation	down-regulates	0.308	Disruption of the hipk2-siah-1 complex is mediated by the atm/atr pathway and involves atm/atr-dependent phosphorylation of siah-1 at ser 19.	SIGNOR-177945
P49841	Q99612	1	phosphorylation	up-regulates activity	0.2	Functionally, GSK3beta enhanced KLF6 mediated growth suppression, which was abrogated by the KLF6-4A phosphomutant.\|These data establish that GSK3\u03b2 directly phosphorylates KLF6, which augments its induction of p21 and resultant growth suppression.	SIGNOR-279373
Q9UQ84	O96017	0	phosphorylation	down-regulates activity	0.565	Inhibition of Exo1 activity by the DDR kinase Rad53.\|Unlike Sae2/CtIP activation by CDK, Exo1 phosphorylation by Rad53 limits extended resection of ssDNA at uncapped telomeres and consequently minimizes further activation of the DDR.	SIGNOR-279028
O43524	Q92574	1	transcriptional regulation	up-regulates quantity	0.448	FoxO3a binds to and transactivates the TSC1 promoter, indicating a key role for FoxO3a in regulating TSC1 expression. Together, these data demonstrate that FoxO3a regulates glycolysis downstream of Akt through transcriptional control of Tsc1	SIGNOR-259382
P30307	Q8TDC3	0	phosphorylation	down-regulates	0.483	Overexpression of hssad1 resulted in an increased phosphorylation of cdc25c on ser-216 in vivo.Phosphorylation of cdc25 triggers cell-cycle arrest by the sequestration of cdc25 by 14-3-3	SIGNOR-56473
P23396	P31749	0	phosphorylation	up-regulates activity	0.368	Here, we show that human RPS3 is a physiological target of Akt kinase and a novel mediator of neuronal apoptosis. NGF stimulation resulted in phosphorylation of threonine 70 of RPS3 by Akt, and this phosphorylation was required for Akt binding to RPS3.our experiment demonstrated that Akt up-regulates the endonuclease activity of RPS3 via phosphorylation and led us to believe that Akt phosphorylation of RPS3 after DNA damage is an antiapoptotic signal or a molecular switch that extends the life of a cell after DNA damage.	SIGNOR-259815
Q92833	P52952	2	binding	down-regulates activity	0.455	JMJ physically associates with Nkx2.5 and GATA4 in vitro and in vivo as determined by glutathione S-transferase pull-down and immunoprecipitation assays. we show that JMJ represses ANF gene expression by inhibiting transcriptional activities of Nkx2.5 and GATA4.	SIGNOR-224787
P06401	P28482	0	phosphorylation	down-regulates	0.605	Phosphorylation of human progesterone receptors at serine-294 by mitogen-activated protein kinase signals their degradation by the 26s proteasome	SIGNOR-74712
O15269	P00519	0	phosphorylation	down-regulates	0.2	We demonstrated that the er-resident human protein serine palmitoyltransferase long chain-1 (sptlc1), which is the first enzyme of sphingolipid biosynthesis, is phosphorylated at tyr(164) by the tyrosine kinase abl. this occurred through the specific abl-mediated phosphorylation of sptlc1 on tyr164, leading to the attenuation of its activity.	SIGNOR-202003
P68400	P83916	1	phosphorylation	down-regulates	0.303	Two recent papers suggest that hp1 recruitment to damage sites, rather than its rapid mobilization, is the predominant behaviour exhibited by this protein. Our findings reconcile recent findings in a new model, wherein rapid hp1beta mobilization from dsbs is mediated by its phosphorylation on thr51 by ck2	SIGNOR-187450
Q9C009	Q15746	1	transcriptional regulation	down-regulates quantity by repression	0.2	Results from this analysis revealed that the inhibitory activity of HFH-1 was contained within the forkhead DNA-binding domain. Truncated HFH-1 proteins that lack the entire forkhead domain were unable to repress telokin promoter activity, in contrast expression of the forkhead domain alone was able to repress promoter activity	SIGNOR-261609
Q15788	P20962	2	binding	up-regulates activity	0.2	Macromolecular translocation inhibitor II (MTI-II), which was first identified as an in vitro inhibitor of binding between the highly purified glucocorticoid receptor (GR) and isolated nuclei, is an 11.5-kDa Zn2+-binding protein that is also known as ZnBP or parathymosin. MTI-II Enhances GR-dependent Transcription through Its Acidic Domain. MTI-II Enhances GR-dependent Transcription in Cooperation with SRC-1 and p300 in Vivo. CBP and p300 Coprecipitate with MTI-II in a Glucocorticoid Hormone-dependent Manner. Immunoprecipitation analysis showed that in the presence of glucocorticoid hormone, p300 and CREB-binding protein are coprecipitated with MTI-II. Furthermore, the knockdown of endogenous MTI-II by RNAi reduces the transcriptional activity of GR in cells.	SIGNOR-268462
Q9BUZ4	O15111	0	phosphorylation	down-regulates	0.384	Traf4 is atypical within its family because it is the only traf family member to negatively regulate innate immune signaling. Ikk_'s phosphorylation of serine-426 on traf4 was required for this negative regulation.	SIGNOR-197253
Q99717	O95257	1	transcriptional regulation	up-regulates quantity	0.2	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-268942
Q96CN5	P51955	0	phosphorylation	down-regulates activity	0.37	Moreover, LRRC45 interacts with both C-Nap1 and rootletin and is phosphorylated by Nek2A at S661 during mitosis. After phosphorylation, both LRRC45 centrosomal localization and fiber-like structures are significantly reduced, which subsequently leads to centrosome separation.	SIGNOR-273707
Q9NS23	P11802	0	phosphorylation	down-regulates	0.409	This skp2-dependent destruction of rassf1a requires phosphorylation of the latter on serine-203 by cyclin d-cyclin-dependent kinase 4.	SIGNOR-159849
P35354	Q13469	0	transcriptional regulation	up-regulates quantity by expression	0.371	NFAT induces the transcription of the COX2 (cyclo-oxygenase-2) gene incancer cells thereby enhancing invasive migration	SIGNOR-264025
Q05655	P06241	0	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
P00734	P01009	2	binding	down-regulates activity	0.423	Alpha1PI, historically known as alpha1-antitrypsin, is a 51 kDa, 394 amino acid glycoprotein, synthesized in the liver, circulating at c. 1.3 mg mL-1 with a half-life of 4.5 days	SIGNOR-263524
Q15391	O95837	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-257210
Q9Y625	Q12968	0	transcriptional regulation	up-regulates quantity by expression	0.2	NFAT transcriptionally regulates GPC6 induction in breast cancer cells and binds to three regulatory elements in the GPC6 proximal promoter. Expression of GPC6 in response to NFAT signalling promotes invasive migration, whereas GPC6 silencing with shRNA (small-hairpin RNA) potently blocks this phenotype.	SIGNOR-264024
P28482	P13056	1	phosphorylation	down-regulates activity	0.2	We also reported that ERK2-phosphorylated TR2 is recruited to PML nuclear bodies (PML NBs) for its subsequent small ubiquitin-like modification (SUMOylation) and function as a potent transcriptional repressor xref , xref .	SIGNOR-278957
P48740	P11226	2	binding	up-regulates activity	0.751	The results (Fig. 3A) show that the anti-MBL antibody, in addition to binding MBL captures both MASP-1 and MASP-2\|Our results emphasize the similarity between complement activation through the MBL, or 'MBLectin' pathway of the innate immune system and the classical pathway of complement activation (Fig. 5).	SIGNOR-263414
P61586	Q2M1Z3	0	gtpase-activating protein	down-regulates activity	0.529	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-260488
P60520	Q14596	2	binding	up-regulates	0.741	We performed glutathione s-transferase (gst) pull-down assays using extracts from hek293 cells overexpressing an ha-tagged nbr1(d50r) mutant, which lacks the ability to bind p62 (lamark et al., 2003) (figures s1a and s1b, available online), and gst fusions of six human atg8 homologs: gabarap, gabarapl1, gabarapl2, lc3a, lc3b, and lc3c. Indeed, nbr1 interacted with all these members of the mammalian atg8 protein family.	SIGNOR-184267
Q8NBJ5	P02452	1	glycosylation	up-regulates activity	0.41	Recombinant GLT25D1 and GLT25D2 enzymes showed a strong galactosyltransferase activity toward various types of collagen and toward the serum mannose-binding lectin MBL, which contains a collagen domain. Amino acid analysis of the products of GLT25D1 and GLT25D2 reactions confirmed the transfer of galactose to hydroxylysine residues.	SIGNOR-261152
P49841	P28482	0	phosphorylation	down-regulates activity	0.383	We demonstrate that insulin-mediated activation of ERK1/2 results in phosphorylation of GSK3β at S9 independently of Akt/mTORC1 activity in Tsc2 null mouse embryonic fibroblasts. In addition, we show that inhibition of ERK1/2 rescues GSK3β activity and restores protein synthesis in Tsc2 −/− MEFs to normal levels	SIGNOR-262524
P16220	Q53ET0	2	binding	up-regulates activity	0.912	The cAMP-response element-binding protein (CREB)-regulated transcription coactivator 2 (CRTC2) is a coactivator known to be specific to CREB and plays a central role in the glucagon-mediated activation of gluconeogenesis in the early phase of fasting	SIGNOR-256102
P24941	O60934	1	phosphorylation	up-regulates activity	0.507	Nbs1 is phosphorylated by Cdk2 on Ser432 in human whole-cell extracts.	SIGNOR-279500
P29350	O60674	1	dephosphorylation	down-regulates activity	0.729	Direct association with and dephosphorylation of Jak2 kinase by the SH2-domain-containing protein tyrosine phosphatase SHP-1	SIGNOR-248466
O43933	Q13608	2	binding	up-regulates activity	0.67	Pex26 recruits Pex6–Pex1 complexes to peroxisomes. Pex26 anchors Pex6 and Pex1 through Pex26–Pex6 and Pex6–Pex1 interactions.	SIGNOR-253615
P20749	P31749	0	phosphorylation	up-regulates quantity by stabilization	0.494	Here we show that Akt, Erk2, and IKK1/2 phosphorylate Bcl3. Phosphorylation of Ser33 by Akt induces switching of K48 ubiquitination to K63 ubiquitination and thus promotes nuclear localization and stabilization of Bcl3. Phosphorylation by Erk2 and IKK1/2 of Ser114 and Ser446 converts Bcl3 into a transcriptional coregulator by facilitating its recruitment to DNA.	SIGNOR-277358
P14598	P13498	2	binding	up-regulates activity	0.79	Stimulus-induced phosphorylation of p47phox causes a conformational change, by which both PX and SH3 domains become accessible to their membranous targets, phosphoinositides and p22phox, respectively. Cooperation of these two interactions, each being indispensable, enables p47phox to form a stable complex with cytochrome b558 (composed of the two subunit gp91phox and p22phox), leading to activation of the phagocyte NADPH oxidase.	SIGNOR-276625
P56945	Q05209	0	dephosphorylation	down-regulates	0.546	Ptp-pest is an efficient negative regulator of lymphocyte activation. This function correlated with the ability of ptp-pest to induce dephosphorylation of shc, pyk2, fak and cas, and inactivate the ras pathway.	SIGNOR-109032
P33076	P14316	0	transcriptional regulation	up-regulates quantity by expression	0.525	In addition to IRF-1, IRF-2, another member of the IRF family, also activates the human CIITA type IV promoter, and IRF-2 cooperates with IRF-1 to activate the promoter in transient transfection assays.	SIGNOR-271681
P41231	P84243	1	demethylation	up-regulates activity	0.2	KDM5 subfamily is capable of removing tri‐ and di‐ methyl marks from lysine 4 on histone H3 (H3K4). Depending on the methylation site, its effect on transcription can be either activating or repressing.	SIGNOR-264307
Q15717	Q05655	0	phosphorylation	up-regulates	0.637	Tandem phosphorylation of serines 221 and 318 by protein kinase cdelta coordinates mrna binding and nucleocytoplasmic shuttling of hurstabilization of mrna by the ubiquitous rna binding protein human antigen r (hur), a member of the embryonic lethal abnormal vision (elav) protein family, requires canonical binding to au-rich element (are)-bearing target mrna and export of nuclear hur-mrna complexes to the cytoplasm. In human mesangial cells (hmc) both processes are induced by angiotensin ii (angii) via protein kinase cdelta (pkcdelta)-triggered serine phosphorylation of hur.	SIGNOR-163524
Q13283	P19525	2	binding	up-regulates activity	0.307	We show that G3BP1 can activate effectors of the innate immune transcriptional program, culminating in enhanced expression of a set of cytokines. We demonstrate that a subset of PKR is recruited to SGs, that close-proximity interactions between G3BP1 and PKR complexes increase in response to stress and PKR activation, that once activated PKR no longer associates with SGs, and that the PXXP domain of G3BP1 is essential for PKR recruitment to SGs and PKR activation in cells. Together, these findings suggest that G3BP1 plays an important role in the recruitment of PKR to SGs and suggest that activation of PKR can take place at the SG.	SIGNOR-260750
P19086	Q9NS75	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-256889
Q6T4R5	Q9NYB9	2	binding	up-regulates activity	0.2	NHS may preferentially bind one or more Abi's in vivo, and it is also likely that specificity is governed by spatiotemporal expression of both proteins. Abi2 is highly expressed in the lens and plays a pivotal role in the development of the anterior and posterior sutures. This suggests that an NHS–Abi2 interaction may be physiologically important for lens development and that null mutations in the NHS gene could cause congenital cataract by disruption of this interaction and the actin cytoskeleton.	SIGNOR-253579
P19086	O95136	2	binding	up-regulates activity	0.385	Here we systematically quantified ligand-induced interactions between 148 GPCRs and all 11 unique G alpha subunit C-termini. For each receptor, we probed chimeric G alpha subunit activation via a transforming growth factor-alpha (TGF alpha) shedding response in HEK293 cells lacking endogenous Gq/11- and G12/13- signaling. \| We defined positive coupling if any member of the subfamily scored LogRAi ≥ -1 and negative coupling if all of the members scored LogRAi < -1 (Figure 3A-B). ROC analysis gives AUC = 0.78 (Figure S4A) when considering high-confidence known coupling data and suggested a threshold of LogRAi ≥ -1.0 for defining true couplings. \| The score associated to this interaction has a LogRAi ≥ -1.0.	SIGNOR-257123
Q05086	P54725	1	polyubiquitination	down-regulates quantity by destabilization	0.486	Here we report the identification of HHR23A, one of the human homologues of the yeast DNA repair protein Rad23, as an E6-independent target of E6AP. E6AP-mediated ubiquitination and degradation of HHR23A and HHR23B.	SIGNOR-272550
P24723	P04083	1	phosphorylation	up-regulates	0.2	The authors identified several phosphorylated residues by a combination of peptide mapping and sequence analysis and showed that recombinant pp60c-src phosphorylates annexin a1 near its amino terminus, at tyrosine 21 (tyr21). Also polyoma virus middle t/pp60c-src complex, recombinant pp50v-abl, and the egf receptor/kinase phosphorylated the same tyrosine residue. It was also shown that serine 27 residue of anxa1 is the primary site phosphorylated by protein kinase c (pkc). In the same study, the threonine 41 residue has been identified as a pkc substrate as well. The adenosine cyclic 3_,5_-phosphate dependent protein kinase a (pka) phosphorylates anxa1 in its carboxyl-terminal core at the threonine 216 residue (thr216) [2].The phosphorylation of serine 27 is essential for annexin a1 membrane localization.	SIGNOR-202792
P02818	P25774	0	cleavage	down-regulates quantity by destabilization	0.309	This study has been undertaken to compare the degradation of BGP by the cysteine proteinases cathepsins L, B, H, S, and the aspartic proteinase cathepsin D. Cathepsins B, L, H, and S readily cleave BGP at the G7-A8 bond; cathepsin L also cleaves at R43-R44; cathepsin B also cleaves at R44-F45; and cathepsin D cleaves only at A41-Y42.	SIGNOR-256323
P24941	Q16584	1	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
Q5T6F0	P43357	2	binding	down-regulates quantity by destabilization	0.2	The CRL4‐DCAF12 E3 ubiquitin ligase degrades MAGE‐A3/6	SIGNOR-272254
P63000	P52306	2	binding	up-regulates	0.485	Smggds has been previously shown to activate a wide variety of small gtpases, including the ras family members rap1a, rap1b, and k-ras, as well as the rho family members cdc42, rac1, rac2, rhoa, and rhob	SIGNOR-171418
Q13153	Q96T58	1	phosphorylation	down-regulates activity	0.2	Pak1 phosphorylation sites in SHARP were mapped to Ser3486 and Thr3568 within the SHARP repression domain.	SIGNOR-278968
P29323	P12931	2	binding	up-regulates	0.566	We propose src kinase as a downstream effector that mediates the neuron's response to eph receptor activation	SIGNOR-58142
P05114	P68400	0	phosphorylation	down-regulates	0.2	Protein kinases that phosphorylate hmg-14 17 at the major sites have been implicated from previous in vitro studies. Protein kinase c and a similar calcium phospholipid-dependent kinase have been reported to phosphorylate both proteins in vitro, where the phosphorylation of hmg-17 occurs predominantly at ser24 and to a lesser degree at ser28. Phosphorylation of hmg-14 at ser6 by camp- or cgmp-dependent kinases has also been reported. Thus, other kinases may contribute to phosphorylation at ser6 in response to oa. Ser88 and ser98 on hmg-14 are also phosphorylated by casein kinase ii in vitro. we conclude that the correlation we observe reflects a causal relationship, in which phosphorylation somehow facilitates the redistribution of hmg-14 and -17 toward non-nuclear pools.	SIGNOR-76274
P43246	P54132	2	binding	up-regulates	0.583	We show that the recombinant hmsh2/6 protein complex stimulated the ability of the bloom's syndrome gene product, blm, to process holliday junctions in vitro	SIGNOR-123699
Q86YT6	Q9NR61	1	ubiquitination	up-regulates activity	0.553	Mib physically interacts with Delta and promotes its ubiquitination and internalization [66], which have been shown to up-regulate Notch activity.	SIGNOR-209626

P45983

P05067

1

phosphorylation

up-regulates

0.71

Phosphorylation of amyloid precursor protein at threonine 668 is essential for its copper-responsive trafficking in sh-sy5y neuroblastoma cells. We found that the threonine 668 within the abetapp intracellular domain (aid or elsewhere aicd) is indeed phosphorylated by jnk1

SIGNOR-117852

P41221

Q8NBF1

0

transcriptional regulation

up-regulates quantity by expression

0.248

GLIS1, a novel hypoxia-inducible transcription factor, promotes breast cancer cell motility via activation of WNT5A

SIGNOR-269040

Q9H4E7

P60953

1

guanine nucleotide exchange factor

up-regulates activity

0.392

Furthermore, membrane targeting of the SLAT Dbl-homology (catalytic) domain was sufficient to trigger TCR-mediated NFAT activation and Th1 and Th2 differentiation in a Cdc42-dependent manner.

SIGNOR-253369

O60928

P17252

0

phosphorylation

down-regulates

0.2

After pharmacological pkc activation, kir7.1 currents were strongly inhibited. Co-application of pkc inhibitors attenuated this effect. Inactivation of pkc consensus sites also strongly attenuated the effect with a single site ((201)s) being essential for almost the total pkc sensitivity.

SIGNOR-181863

Q07912

P09619

0

phosphorylation

up-regulates activity

0.359

Mutational analysis suggested that Y635 of ACK1 is a PDGFR-β phosphorylation site and that the ACK1 Y635F mutant abrogated the sequential activation of AKT.

SIGNOR-276854

O60610

P06493

0

phosphorylation

down-regulates activity

0.2

In this study, we found that Cdk1 phosphorylated DIAPH1, which inhibited the interaction between DIAPH1 and profilin1 (PFN1) during metaphase.|Thus, the results suggest that the level of cortical F-actin has to be finely maintained by Cdk1 mediated positive and negative regulation of DIAPH1.

SIGNOR-279598

P12931

Q01973

0

phosphorylation

up-regulates

0.318

Ror1 binds to and phosphorylates c-src / ror1 kinase-dependent c-src activation

SIGNOR-196751

P52333

2

phosphorylation

up-regulates

0.2

The phosphorylation of wt jak3 and y980f/y981f/y785f mutant jak3 is presumably mediated through autophosphorylation at distinct jak3 sites within this model systemhosphorylation of jak3 on y785 has been reported to create a binding site for the adaptor protein sh2b-beta

SIGNOR-160660

Q9UNS2

Q07889

2

binding

up-regulates quantity by stabilization

0.2

Our observations characterizing the interaction between CSN3 and the Sos1 HD suggest that this domain not only functions regulating Sos-GEF autoinhibition but is also involved in other functional roles, such as the control of Sos protein stability and homeostasis by modulating the degradation and intracellular levels of Sos1.

SIGNOR-256217

P61586

Q3KR16

0

guanine nucleotide exchange factor

up-regulates activity

0.583

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

SIGNOR-260567

Q8TBJ4

Q0VAM2

2

binding

up-regulates activity

0.2

Oncogenic effects of imbalanced PRG3 are mediated via PRG3-RasGEF1 interaction and Ras activation. PRG3 interacts with RasGEF1 in vivo.We could further show that PRG3 executes the binding to RasGEF1 predominantly via its C-terminal domain (CT) and in the consequence causes Ras activation.

SIGNOR-261806

Q8NBP7

Q8IXL6

0

phosphorylation

up-regulates activity

0.537

Herein, we report that Fam20C and Fam20A significantly eliminate the Furin-cleavage of PCSK9 (XREF_FIG, lanes 5, 6), thereby enhancing the pPCSK9 activity|Herein, we show that Fam20C phosphorylates PCSK9 at Serines 47, 666, 668 and 688.

SIGNOR-278935

Q969F8

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-256893

P63096

P60953

2

binding

up-regulates activity

0.523

These findings indicate that both G alpha(i) and G beta gamma stimulate Rac and Cdc42 pathways with lysophosphatidic acid-induced cell spreading on fibronectin

SIGNOR-256531

Q92934

P17252

0

phosphorylation

down-regulates activity

0.2

Phosphorylation of BAD at ser112 and ser136 in the setting of lapatinib treatment was fully restored by PRKACA expression in BT474, SKBr3, and ZR-75-30 cells (XREF_FIG).|We found that neither PRKACA nor PIM1 restored MAPK or PI3K activation after lapatinib or trastuzumab treatment, but rather inactivated the pro apoptotic protein BAD, thereby permitting survival signaling through BCL-XL.

SIGNOR-280080

Q12899

P78549

1

ubiquitination

down-regulates quantity by destabilization

0.263

We also demonstrated that TRIM26 directly polyubiquitylates NTH1 in cells and that TRIM26 targets newly synthesized NTH1 protein for ubiquitylation dependent degradation.

SIGNOR-278733

Q9Y5G1

Q9Y5H9

2

binding

up-regulates activity

0.2

The clustered protocadherins comprise the largest subfamily of the cadherin superfamily and are predominantly expressed in the nervous system. Pcdh-alpha proteins interact with beta1-integrin to promote cell adhesion. They also form oligomers with Pcdh-gamma proteins at the same membrane sites.

SIGNOR-265685

P12931

O15530

1

phosphorylation

up-regulates activity

0.585

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

SIGNOR-109533

O15013

P60953

1

guanine nucleotide exchange factor

up-regulates activity

0.499

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-260537

P15173

P38936

1

transcriptional regulation

down-regulates quantity by repression

0.331

P21 is regulated by MyoD and myogenin in normal muscle cells and the inactivation of these factors in RMS cells contributes to the silencing of p21 in RMS cells

SIGNOR-251575

Q9NPG1

O00755

2

binding

up-regulates activity

0.646

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-131897

P63096

O14939

2

binding

down-regulates

0.307

The results of this study suggest that membrane phospholipase d activity can be negatively regulated via gi

SIGNOR-48256

O43524

P45983

0

phosphorylation

up-regulates activity

0.65

As JNK1 phosphorylates FOXO3 at S574, 12 allowing formation of the proapoptotic species, we tested whether FOXO3 acetylation is required for the JNK1-FOXO3 interaction.

SIGNOR-280030

P31943

P12931

1

post transcriptional regulation

up-regulates quantity by expression

0.291

HnRNP H is a component of a splicing enhancer complex that activates a c-src alternative exon in neuronal cells.

SIGNOR-261273

P30291

Q9UNH5

0

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

O43395

Q13107

0

deubiquitination

down-regulates activity

0.487

Prp3 is deubiquitinated by Usp4 and its substrate targeting factor, the U4/U6 recycling protein Sart3, which likely facilitates ejection of U4 proteins from the spliceosome during maturation of its active site.

SIGNOR-271975

P24928

P50613

0

phosphorylation

down-regulates

0.789

Although there is some inconsistency in the literature, it is generally thought that cdk7, a component of the transcription factor (tf) iih, is a major ser-5 kinase, whereas cdk9, a component of positive transcription elongation factor (p-tef) b, is a major ser-2 kinase within cells. These results suggest that subsequent to h2o2 treatment, the ser-5-phosphorylated form, but not the ser-2-phosphorylated form or the unphosphorylated form, is targeted for rapid proteasomal degradation through its ubiquitination.

SIGNOR-120024

P68431

Q96T68

0

methylation

up-regulates activity

0.2

Here, we have characterized a previously undescribed member of the histone H3K9 methyltransferase family named CLLD8 (or SETDB2 or KMT1F). This protein contributes to the trimethylation of both interspersed repetitive elements and centromere-associated repeats and participates in the recruitment of heterochromatin protein 1 to centromeres. Methylation of histone H3 at lysine 9 (H3K9) has emerged as an important player in the formation of heterochromatin, chromatin condensation, and transcriptional repression.

SIGNOR-263896

P68400

Q13283

1

phosphorylation

down-regulates activity

0.239

We also show that casein kinase 2 phosphorylates G3BP1 at serine 149 in vitro and in cells. These data support a role for casein kinase 2 in regulation of protein synthesis by downregulating stress granule formation through G3BP1.CK2 regulates SG disassembly during stress recovery.G3BP1 is among the strongest SG nucleating proteins, and previous work indicated that G3BP1 phosphorylation at S149 restricts stress granule assembly by partly inhibiting G3BP1 oligomerization

SIGNOR-260748

P60953

Q3KRB8

0

gtpase-activating protein

down-regulates activity

0.49

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-260468

P07947

P09086

1

phosphorylation

up-regulates activity

0.2

These data suggest that Yes1 is the TKI-sensitive kinase that can directly phosphorylate OCT2.

SIGNOR-279664

Q96T51

P20338

2

binding

up-regulates activity

0.68

Here, we have demonstrated that Rab14 interacts with RUFY1, previously identified as a Rab4 effector, and is required for RUFY1 recruitment onto endosomes and efficient recycling of Tfn.|We also found that enlargement of early endosomes mediated by RUFY1 requires its interaction with Rab4

SIGNOR-261280

P07900

P37173

2

binding

up-regulates

0.384

The data in fig. 5 suggest that hsp90 specifically interacts with t?RI And t?RII In vitro and in vivo. Coupled with our data showing that loss of hsp90 function decreases t?R Levels and blocks tgf?-Induced smad2/3 activation and transcription, this result suggests that hsp90 controls tgf? Signaling as an essential component for stabilizing t?Rs.

SIGNOR-179271

O43255

Q16539

0

phosphorylation

up-regulates

0.2

We show that siah2 is subject to phosphorylation by p38 mapk, which increases siah2-mediated degradation of phd3.

SIGNOR-149890

Q13526

P53350

0

phosphorylation

up-regulates

0.424

Here we demonstrate that ser-65 in pin1 is the major site for plk1-specific phosphorylation, and the polo-box domain of plk1 is required for this phosphorylation. Interestingly, the phosphorylation of pin1 by plk1 does not affect its isomerase activity but rather is linked to its protein stability. pin1 is ubiquitinated in hela s3 cells, and substitution of glu for ser-65 reduces the ubiquitination of pin1.

SIGNOR-139919

P17612

O14649

1

phosphorylation

up-regulates activity

0.2

Mutation of the ser393 to alanine, which can neither be phosphorylated nor mimic a phosphorylated residue, resulted in the channel failing to pass current all of our findings support the conclusion that camp-dependent protein kinase is responsible for the phosphorylation of the terminal serine in both k2p3.1 and k2p9.1.

SIGNOR-172430

P17252

Q15172

1

phosphorylation

down-regulates activity

0.341

In this study, we identified a novel phosphorylation site at Ser(41) of B56α. This phosphoamino acid residue was efficiently phosphorylated in vitro by PKCα.

SIGNOR-276603

Q9NRA0

P27361

0

phosphorylation

up-regulates

0.521

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-153387

O43524

P11309

0

phosphorylation

down-regulates activity

0.387

Pim1s expression induced the phosphorylation of foxo3a (fig. 5a and b) and inactivated its transcriptional activity (fig. 5c). A previous report showed that phosphorylation at t32, s253, and s315 residues in foxo3a induced 14-3-3 binding, nuclear export, and proteasomemediated degradation (42).

SIGNOR-179308

Q96QS3

P17252

0

phosphorylation

up-regulates activity

0.2

We confirm that ARX is phosphorylated by PRKCA and demonstrate phosphorylation at serine 174. We demonstrate that phosphorylation is required for correct transcriptional activity of the ARX protein using transcriptome-wide analysis of gene expression of phospho-null mutants (alanines replacing serines) compared to ARX wild-type (ARX-WT) overexpressed in pancreatic alpha TC cells.

SIGNOR-277418

Q9BYB0

Q9Y2H0

0

relocalization

up-regulates activity

0.2

SHANK proteins are ‘master’ scaffolding proteins that tether and organize intermediate scaffolding proteins. They are located at excitatory synapses, where they are crucial for proper synaptic development and function. SAPAP proteins subsequently bind to the PDZ domain of members of the SHANK protein family. SHANK proteins then bind to the actin cytoskeleton and to Homer protein, which in turn interacts with mGluRs. Through these extended links, PSD95, SAPAP, SHANK and Homer proteins form a quaternary complex that brings together mGluR and NMDAR complexes in the PSD (FIG. 3).

SIGNOR-264597

P49841

Q96RG2

0

phosphorylation

down-regulates activity

0.288

In vitro, PASK directly phosphorylates GSK3\u03b2 on its inactivating phosphorylation site Ser(9).|We conclude that PASK phosphorylates and inactivates GSK3\u03b2, thereby preventing PDX-1 serine phosphorylation and alleviating GSK3\u03b2-mediated PDX-1 protein degradation in pancreatic \u03b2-cells.

SIGNOR-279639

Q96S59

Q13315

0

phosphorylation

up-regulates activity

0.439

We demonstrate that ATM phosphorylates RanBP9 in response to Ionizing Radiation and mediates its nuclear accumulation.

SIGNOR-279005

P09471

P30550

2

binding

up-regulates activity

0.268

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-257247

Q9Y478

Q13131

0

phosphorylation

up-regulates

0.925

Mutation of serine 108 to alanine, an autophosphorylation site within the glycogen binding domain of the beta1 subunit, almost completely abolishes activation of ampk by a-769662 in cells and in vitro, while only partially reducing activation by amp

SIGNOR-157553

P84243

P41231

0

demethylation

up-regulates activity

0.2

KDM5 subfamily is capable of removing tri‐ and di‐ methyl marks from lysine 4 on histone H3 (H3K4). Depending on the methylation site, its effect on transcription can be either activating or repressing.

SIGNOR-264307

P03372

Q13153

0

phosphorylation

up-regulates

0.534

Pak1 directly phosphorylated the activation function-2 domain of the er at the n-terminal residue ser305, and its mutation to ala (s305a) abolished the pak1-mediated phosphorylation and transactivation functions of the er

SIGNOR-94206

P32004

P17252

0

phosphorylation

down-regulates activity

0.2

CKII phosphorylates T1172 of the L1 CD and phosphorylation of T1172 is responsible for loss of 2C2 signal.

SIGNOR-276283

Q8IUQ4

Q13315

0

phosphorylation

down-regulates

0.308

Disruption of the hipk2-siah-1 complex is mediated by the atm/atr pathway and involves atm/atr-dependent phosphorylation of siah-1 at ser 19.

SIGNOR-177945

P49841

Q99612

1

phosphorylation

up-regulates activity

0.2

Functionally, GSK3beta enhanced KLF6 mediated growth suppression, which was abrogated by the KLF6-4A phosphomutant.|These data establish that GSK3\u03b2 directly phosphorylates KLF6, which augments its induction of p21 and resultant growth suppression.

SIGNOR-279373

Q9UQ84

O96017

0

phosphorylation

down-regulates activity

0.565

Inhibition of Exo1 activity by the DDR kinase Rad53.|Unlike Sae2/CtIP activation by CDK, Exo1 phosphorylation by Rad53 limits extended resection of ssDNA at uncapped telomeres and consequently minimizes further activation of the DDR.

SIGNOR-279028

O43524

Q92574

1

transcriptional regulation

up-regulates quantity

0.448

FoxO3a binds to and transactivates the TSC1 promoter, indicating a key role for FoxO3a in regulating TSC1 expression. Together, these data demonstrate that FoxO3a regulates glycolysis downstream of Akt through transcriptional control of Tsc1

SIGNOR-259382

P30307

Q8TDC3

0

phosphorylation

down-regulates

0.483

Overexpression of hssad1 resulted in an increased phosphorylation of cdc25c on ser-216 in vivo.Phosphorylation of cdc25 triggers cell-cycle arrest by the sequestration of cdc25 by 14-3-3

SIGNOR-56473

P23396

P31749

0

phosphorylation

up-regulates activity

0.368

Here, we show that human RPS3 is a physiological target of Akt kinase and a novel mediator of neuronal apoptosis. NGF stimulation resulted in phosphorylation of threonine 70 of RPS3 by Akt, and this phosphorylation was required for Akt binding to RPS3.our experiment demonstrated that Akt up-regulates the endonuclease activity of RPS3 via phosphorylation and led us to believe that Akt phosphorylation of RPS3 after DNA damage is an antiapoptotic signal or a molecular switch that extends the life of a cell after DNA damage.

SIGNOR-259815

Q92833

P52952

2

binding

down-regulates activity

0.455

JMJ physically associates with Nkx2.5 and GATA4 in vitro and in vivo as determined by glutathione S-transferase pull-down and immunoprecipitation assays. we show that JMJ represses ANF gene expression by inhibiting transcriptional activities of Nkx2.5 and GATA4.

SIGNOR-224787

P06401

P28482

0

phosphorylation

down-regulates

0.605

Phosphorylation of human progesterone receptors at serine-294 by mitogen-activated protein kinase signals their degradation by the 26s proteasome

SIGNOR-74712

O15269

P00519

0

phosphorylation

down-regulates

0.2

We demonstrated that the er-resident human protein serine palmitoyltransferase long chain-1 (sptlc1), which is the first enzyme of sphingolipid biosynthesis, is phosphorylated at tyr(164) by the tyrosine kinase abl. this occurred through the specific abl-mediated phosphorylation of sptlc1 on tyr164, leading to the attenuation of its activity.

SIGNOR-202003

P68400

P83916

1

phosphorylation

down-regulates

0.303

Two recent papers suggest that hp1 recruitment to damage sites, rather than its rapid mobilization, is the predominant behaviour exhibited by this protein. Our findings reconcile recent findings in a new model, wherein rapid hp1beta mobilization from dsbs is mediated by its phosphorylation on thr51 by ck2

SIGNOR-187450

Q9C009

Q15746

1

transcriptional regulation

down-regulates quantity by repression

0.2

Results from this analysis revealed that the inhibitory activity of HFH-1 was contained within the forkhead DNA-binding domain. Truncated HFH-1 proteins that lack the entire forkhead domain were unable to repress telokin promoter activity, in contrast expression of the forkhead domain alone was able to repress promoter activity

SIGNOR-261609

Q15788

P20962

2

binding

up-regulates activity

0.2

Macromolecular translocation inhibitor II (MTI-II), which was first identified as an in vitro inhibitor of binding between the highly purified glucocorticoid receptor (GR) and isolated nuclei, is an 11.5-kDa Zn2+-binding protein that is also known as ZnBP or parathymosin. MTI-II Enhances GR-dependent Transcription through Its Acidic Domain. MTI-II Enhances GR-dependent Transcription in Cooperation with SRC-1 and p300 in Vivo. CBP and p300 Coprecipitate with MTI-II in a Glucocorticoid Hormone-dependent Manner. Immunoprecipitation analysis showed that in the presence of glucocorticoid hormone, p300 and CREB-binding protein are coprecipitated with MTI-II. Furthermore, the knockdown of endogenous MTI-II by RNAi reduces the transcriptional activity of GR in cells.

SIGNOR-268462

Q9BUZ4

O15111

0

phosphorylation

down-regulates

0.384

Traf4 is atypical within its family because it is the only traf family member to negatively regulate innate immune signaling. Ikk_'s phosphorylation of serine-426 on traf4 was required for this negative regulation.

SIGNOR-197253

Q99717

O95257

1

transcriptional regulation

up-regulates quantity

0.2

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-268942

Q96CN5

P51955

0

phosphorylation

down-regulates activity

0.37

Moreover, LRRC45 interacts with both C-Nap1 and rootletin and is phosphorylated by Nek2A at S661 during mitosis. After phosphorylation, both LRRC45 centrosomal localization and fiber-like structures are significantly reduced, which subsequently leads to centrosome separation.

SIGNOR-273707

Q9NS23

P11802

0

phosphorylation

down-regulates

0.409

This skp2-dependent destruction of rassf1a requires phosphorylation of the latter on serine-203 by cyclin d-cyclin-dependent kinase 4.

SIGNOR-159849

P35354

Q13469

0

transcriptional regulation

up-regulates quantity by expression

0.371

NFAT induces the transcription of the COX2 (cyclo-oxygenase-2) gene incancer cells thereby enhancing invasive migration

SIGNOR-264025

Q05655

P06241

0

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

P00734

P01009

2

binding

down-regulates activity

0.423

Alpha1PI, historically known as alpha1-antitrypsin, is a 51 kDa, 394 amino acid glycoprotein, synthesized in the liver, circulating at c. 1.3 mg mL-1 with a half-life of 4.5 days

SIGNOR-263524

Q15391

O95837

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-257210

Q9Y625

Q12968

0

transcriptional regulation

up-regulates quantity by expression

0.2

NFAT transcriptionally regulates GPC6 induction in breast cancer cells and binds to three regulatory elements in the GPC6 proximal promoter. Expression of GPC6 in response to NFAT signalling promotes invasive migration, whereas GPC6 silencing with shRNA (small-hairpin RNA) potently blocks this phenotype.

SIGNOR-264024

P28482

P13056

1

phosphorylation

down-regulates activity

0.2

We also reported that ERK2-phosphorylated TR2 is recruited to PML nuclear bodies (PML NBs) for its subsequent small ubiquitin-like modification (SUMOylation) and function as a potent transcriptional repressor xref , xref .

SIGNOR-278957

P48740

P11226

2

binding

up-regulates activity

0.751

The results (Fig. 3A) show that the anti-MBL antibody, in addition to binding MBL captures both MASP-1 and MASP-2|Our results emphasize the similarity between complement activation through the MBL, or 'MBLectin' pathway of the innate immune system and the classical pathway of complement activation (Fig. 5).

SIGNOR-263414

P61586

Q2M1Z3

0

gtpase-activating protein

down-regulates activity

0.529

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-260488

P60520

Q14596

2

binding

up-regulates

0.741

We performed glutathione s-transferase (gst) pull-down assays using extracts from hek293 cells overexpressing an ha-tagged nbr1(d50r) mutant, which lacks the ability to bind p62 (lamark et al., 2003) (figures s1a and s1b, available online), and gst fusions of six human atg8 homologs: gabarap, gabarapl1, gabarapl2, lc3a, lc3b, and lc3c. Indeed, nbr1 interacted with all these members of the mammalian atg8 protein family.

SIGNOR-184267

Q8NBJ5

P02452

1

glycosylation

up-regulates activity

0.41

Recombinant GLT25D1 and GLT25D2 enzymes showed a strong galactosyltransferase activity toward various types of collagen and toward the serum mannose-binding lectin MBL, which contains a collagen domain. Amino acid analysis of the products of GLT25D1 and GLT25D2 reactions confirmed the transfer of galactose to hydroxylysine residues.

SIGNOR-261152

P49841

P28482

0

phosphorylation

down-regulates activity

0.383

We demonstrate that insulin-mediated activation of ERK1/2 results in phosphorylation of GSK3β at S9 independently of Akt/mTORC1 activity in Tsc2 null mouse embryonic fibroblasts. In addition, we show that inhibition of ERK1/2 rescues GSK3β activity and restores protein synthesis in Tsc2 −/− MEFs to normal levels

SIGNOR-262524

P16220

Q53ET0

2

binding

up-regulates activity

0.912

The cAMP-response element-binding protein (CREB)-regulated transcription coactivator 2 (CRTC2) is a coactivator known to be specific to CREB and plays a central role in the glucagon-mediated activation of gluconeogenesis in the early phase of fasting

SIGNOR-256102

P24941

O60934

1

phosphorylation

up-regulates activity

0.507

Nbs1 is phosphorylated by Cdk2 on Ser432 in human whole-cell extracts.

SIGNOR-279500

P29350

O60674

1

dephosphorylation

down-regulates activity

0.729

Direct association with and dephosphorylation of Jak2 kinase by the SH2-domain-containing protein tyrosine phosphatase SHP-1

SIGNOR-248466

O43933

Q13608

2

binding

up-regulates activity

0.67

Pex26 recruits Pex6–Pex1 complexes to peroxisomes. Pex26 anchors Pex6 and Pex1 through Pex26–Pex6 and Pex6–Pex1 interactions.

SIGNOR-253615

P20749

P31749

0

phosphorylation

up-regulates quantity by stabilization

0.494

Here we show that Akt, Erk2, and IKK1/2 phosphorylate Bcl3. Phosphorylation of Ser33 by Akt induces switching of K48 ubiquitination to K63 ubiquitination and thus promotes nuclear localization and stabilization of Bcl3. Phosphorylation by Erk2 and IKK1/2 of Ser114 and Ser446 converts Bcl3 into a transcriptional coregulator by facilitating its recruitment to DNA.

SIGNOR-277358

P14598

P13498

2

binding

up-regulates activity

0.79

Stimulus-induced phosphorylation of p47phox causes a conformational change, by which both PX and SH3 domains become accessible to their membranous targets, phosphoinositides and p22phox, respectively. Cooperation of these two interactions, each being indispensable, enables p47phox to form a stable complex with cytochrome b558 (composed of the two subunit gp91phox and p22phox), leading to activation of the phagocyte NADPH oxidase.

SIGNOR-276625

P56945

Q05209

0

dephosphorylation

down-regulates

0.546

Ptp-pest is an efficient negative regulator of lymphocyte activation. This function correlated with the ability of ptp-pest to induce dephosphorylation of shc, pyk2, fak and cas, and inactivate the ras pathway.

SIGNOR-109032

P33076

P14316

0

transcriptional regulation

up-regulates quantity by expression

0.525

In addition to IRF-1, IRF-2, another member of the IRF family, also activates the human CIITA type IV promoter, and IRF-2 cooperates with IRF-1 to activate the promoter in transient transfection assays.

SIGNOR-271681

P41231

P84243

1

demethylation

up-regulates activity

0.2

KDM5 subfamily is capable of removing tri‐ and di‐ methyl marks from lysine 4 on histone H3 (H3K4). Depending on the methylation site, its effect on transcription can be either activating or repressing.

SIGNOR-264307

Q15717

Q05655

0

phosphorylation

up-regulates

0.637

Tandem phosphorylation of serines 221 and 318 by protein kinase cdelta coordinates mrna binding and nucleocytoplasmic shuttling of hurstabilization of mrna by the ubiquitous rna binding protein human antigen r (hur), a member of the embryonic lethal abnormal vision (elav) protein family, requires canonical binding to au-rich element (are)-bearing target mrna and export of nuclear hur-mrna complexes to the cytoplasm. In human mesangial cells (hmc) both processes are induced by angiotensin ii (angii) via protein kinase cdelta (pkcdelta)-triggered serine phosphorylation of hur.

SIGNOR-163524

Q13283

P19525

2

binding

up-regulates activity

0.307

We show that G3BP1 can activate effectors of the innate immune transcriptional program, culminating in enhanced expression of a set of cytokines. We demonstrate that a subset of PKR is recruited to SGs, that close-proximity interactions between G3BP1 and PKR complexes increase in response to stress and PKR activation, that once activated PKR no longer associates with SGs, and that the PXXP domain of G3BP1 is essential for PKR recruitment to SGs and PKR activation in cells. Together, these findings suggest that G3BP1 plays an important role in the recruitment of PKR to SGs and suggest that activation of PKR can take place at the SG.

SIGNOR-260750

P19086

Q9NS75

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-256889

Q6T4R5

Q9NYB9

2

binding

up-regulates activity

0.2

NHS may preferentially bind one or more Abi's in vivo, and it is also likely that specificity is governed by spatiotemporal expression of both proteins. Abi2 is highly expressed in the lens and plays a pivotal role in the development of the anterior and posterior sutures. This suggests that an NHS–Abi2 interaction may be physiologically important for lens development and that null mutations in the NHS gene could cause congenital cataract by disruption of this interaction and the actin cytoskeleton.

SIGNOR-253579

P19086

O95136

2

binding

up-regulates activity

0.385

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

SIGNOR-257123

Q05086

P54725

1

polyubiquitination

down-regulates quantity by destabilization

0.486

Here we report the identification of HHR23A, one of the human homologues of the yeast DNA repair protein Rad23, as an E6-independent target of E6AP. E6AP-mediated ubiquitination and degradation of HHR23A and HHR23B.

SIGNOR-272550

P24723

P04083

1

phosphorylation

up-regulates

0.2

The authors identified several phosphorylated residues by a combination of peptide mapping and sequence analysis and showed that recombinant pp60c-src phosphorylates annexin a1 near its amino terminus, at tyrosine 21 (tyr21). Also polyoma virus middle t/pp60c-src complex, recombinant pp50v-abl, and the egf receptor/kinase phosphorylated the same tyrosine residue. It was also shown that serine 27 residue of anxa1 is the primary site phosphorylated by protein kinase c (pkc). In the same study, the threonine 41 residue has been identified as a pkc substrate as well. The adenosine cyclic 3_,5_-phosphate dependent protein kinase a (pka) phosphorylates anxa1 in its carboxyl-terminal core at the threonine 216 residue (thr216) [2].The phosphorylation of serine 27 is essential for annexin a1 membrane localization.

SIGNOR-202792

P02818

P25774

0

cleavage

down-regulates quantity by destabilization

0.309

This study has been undertaken to compare the degradation of BGP by the cysteine proteinases cathepsins L, B, H, S, and the aspartic proteinase cathepsin D. Cathepsins B, L, H, and S readily cleave BGP at the G7-A8 bond; cathepsin L also cleaves at R43-R44; cathepsin B also cleaves at R44-F45; and cathepsin D cleaves only at A41-Y42.

SIGNOR-256323

P24941

Q16584

1

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

Q5T6F0

P43357

2

binding

down-regulates quantity by destabilization

0.2

The CRL4‐DCAF12 E3 ubiquitin ligase degrades MAGE‐A3/6

SIGNOR-272254

P63000

P52306

2

binding

up-regulates

0.485

Smggds has been previously shown to activate a wide variety of small gtpases, including the ras family members rap1a, rap1b, and k-ras, as well as the rho family members cdc42, rac1, rac2, rhoa, and rhob

SIGNOR-171418

Q13153

Q96T58

1

phosphorylation

down-regulates activity

0.2

Pak1 phosphorylation sites in SHARP were mapped to Ser3486 and Thr3568 within the SHARP repression domain.

SIGNOR-278968

P29323

P12931

2

binding

up-regulates

0.566

We propose src kinase as a downstream effector that mediates the neuron's response to eph receptor activation

SIGNOR-58142

P05114

P68400

0

phosphorylation

down-regulates

0.2

Protein kinases that phosphorylate hmg-14 17 at the major sites have been implicated from previous in vitro studies. Protein kinase c and a similar calcium phospholipid-dependent kinase have been reported to phosphorylate both proteins in vitro, where the phosphorylation of hmg-17 occurs predominantly at ser24 and to a lesser degree at ser28. Phosphorylation of hmg-14 at ser6 by camp- or cgmp-dependent kinases has also been reported. Thus, other kinases may contribute to phosphorylation at ser6 in response to oa. Ser88 and ser98 on hmg-14 are also phosphorylated by casein kinase ii in vitro. we conclude that the correlation we observe reflects a causal relationship, in which phosphorylation somehow facilitates the redistribution of hmg-14 and -17 toward non-nuclear pools.

SIGNOR-76274

P43246

P54132

2

binding

up-regulates

0.583

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

SIGNOR-123699

Q86YT6

Q9NR61

1

ubiquitination

up-regulates activity

0.553

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

SIGNOR-209626