GleghornLab/Signor_2class · Datasets at Hugging Face

IdA string	IdB string	labels int64	mechanism string	effect string	score float64	sentence string	signor_id string
P07948	P19174	1	phosphorylation	up-regulates activity	0.656	The phosphorylation of purified phospholipase C-gamma 1 (PLC-gamma 1) and PLC-gamma 2 by src-family-protein tyrosine kinases (PTKs) P56lck, p53/56lyn, p59hck, p59fyn, and p60src was studied in vitro. All five PTKs phosphorylated PLC-gamma 1 and PLC-gamma 2, suggesting that both PLC-gamma isozymes can be phosphorylated in cells by any of the src-family PTKs in response to the activation of cell surface receptors.	SIGNOR-249381
O95239	P53350	0	phosphorylation	down-regulates activity	0.467	Moreover, phosphorylation of KIF4 and condensin I by Aurora B and polo like kinase 1 (Plk1) is important for KIF4 and condensin I localization to the chromosome.\|These results suggest that Plk1 negatively regulates the loading of both KIF4 and condensin to the chromosome.	SIGNOR-280069
P29350	P63261	1	dephosphorylation	down-regulates	0.2	Our data suggest that shp-1 plays a pivotal role in reorganization of cytoskeletal architecture inducing actin dephosphorylation. These results clearly demonstrate the direct interaction of shp-1 with actin	SIGNOR-99565
P06493	Q8NFH5	1	phosphorylation	down-regulates activity	0.563	Collectively, these data show that mitotic hyperphosphorylation of Nup53 by CDK1 and PLK1 contributes to its removal from NPCs.\|The combined mutation of the CDK1 and PLK1 sites to phosphomimetic residues almost completely abolished NPC integration of Nup53, indicating that hyperphosphorylation of Nup53 might be incompatible with its NPC association.	SIGNOR-278917
Q9UQ26	P20336	1	relocalization	up-regulates activity	0.762	N-terminal interactions of RIMs with RAB3 and MUNC13 regulate DCV fusion. Through N-terminal interactions, RIMs position MUNC13 and recruit DCVs via RAB3, which is located on the vesicle	SIGNOR-264377
Q92626	Q16236	0	transcriptional regulation	up-regulates quantity by expression	0.2	PXDN expression in response to H2O2 and the Nrf2-specific inducers, tert-butylhydroquinone (tBHQ) and sulforaphane (SFN), was determined by western blotting and immunofluorescence microscopy, in HeLa and HEK293 cells.We found that Nrf2 binds to and increases luciferase reporter gene expression from the PXDN promoter via a putative Nrf2-binding site. In summary, we show that PXDN is a novel target of the redox sensitive transcription factor Nrf2.	SIGNOR-265248
O14640	Q9NQ66	1	null	up-regulates activity	0.275	Dsh through PLC activates IP3, which leads to release of intracellular Ca2+, which in turn activates CamK11 and calcineurin	SIGNOR-258978
Q13546	Q96AX9	0	ubiquitination	down-regulates quantity by destabilization	0.295	These data suggest that after binding, MIB2 inhibits RIPK1 through a mechanism that is dependent on the E3 ligase activity of MIB2.\|Whereas MIB2 readily ubiquitylated wild-type RIPK1, mutating K377 to R significantly reduced MIB2 mediated ubiquitylation of RIPK1 (XREF_SUPPLEMENTARY A).	SIGNOR-278633
Q05D32	Q8TDR2	1	dephosphorylation	up-regulates quantity by stabilization	0.282	We found that peptides corresponding to phosphoserines 194 and 216 of PDIK1L (S385 and S413 of STK35) were efficiently dephosphorylated by SCP4, whereas no activity was detected for the other two phosphopeptides (Figure 6D).	SIGNOR-273775
P17252	P35612	1	phosphorylation	down-regulates	0.2	We now demonstrate that ptn stimulates the phosphorylation of serines 713 and 726 in the myristoylated alanine-rich protein kinase (pk) c substrate domain of beta-adducin through activation of either pkc alpha or beta.	SIGNOR-139870
Q14586	P09238	1	transcriptional regulation	down-regulates quantity by repression	0.39	Furthermore, ZNF267 binds to the MMP-10 promoter region as demonstrated by chromatin immunoprecipitation assays. In conclusion, our results suggest that ZNF267 as a negative transcriptional regulator of MMP-10	SIGNOR-266211
P27361	Q14934	1	phosphorylation	up-regulates	0.289	The formation of rsk-nfatc4-dna transcription complex is also apparent upon adipogenesis. Bound rsk phosphorylates ser(676) and potentiates nfatc4 dna binding by escalating nfat-dna association. Ser(676) is also targeted by the erk map kinase, which interacts with nfat at a distinct region than rsk. Thus, integration of the erk/rsk signaling pathway provides a mechanism to modulate nfatc4 transcription activity.	SIGNOR-133276
P04637	O95155	0	polyubiquitination	down-regulates quantity by destabilization	0.396	We show that ubiquitination factor E4B (UBE4B), an E3 and E4 ubiquitin ligase, physically interacts with p53 and Hdm2 (also known as Mdm2 in mice). UBE4B promotes p53 polyubiquitination and degradation and inhibits p53-dependent transactivation and apoptosis.	SIGNOR-271907
P61586	Q86VW2	0	guanine nucleotide exchange factor	up-regulates activity	0.835	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-260544
Q04759	P32942	1	phosphorylation	up-regulates activity	0.334	Ser489 was a phosphorylation site in vitro for recombinant protein kinase Ctheta. Finally, treatment of Jurkat cells with chelerythrine chloride, a protein kinase C inhibitor, prevented ICAM-3-triggered spreading.	SIGNOR-248979
P49841	P10275	1	phosphorylation	down-regulates activity	0.649	Glycogen synthase kinase-3 beta is involved in the phosphorylation and suppression of androgen receptor activity.\|In particular, we showed that glycogen synthase kinase-3 beta phosphorylates the androgen receptor, thereby inhibiting androgen receptor-driven transcription.	SIGNOR-279334
Q4VCS5	P46937	1	relocalization	down-regulates	0.734	Yap/taz and angiomotin (amot) family proteins were shown to interact, resulting in yap/taz localization to tight junctions and inhibition through phosphorylation-dependent and -independent mechanisms.	SIGNOR-175779
P57059	P49841	0	phosphorylation	up-regulates activity	0.2	Glycogen synthase kinase-3beta (GSK-3beta) phosphorylates Ser/Thr residues located at the fourth position ahead of the pre-phosphorylated Ser/Thr residues, and inhibitors of GSK-3beta reduce the phosphorylation at Thr182. The results of an in vitro reconstitution assay also indicate that GSK-3beta could be the SIK1 kinase. However, overexpression and knockdown of GSK-3beta in LKB1-defective HeLa cells suggests that GSK-3beta alone may not be able to phosphorylate or activate SIK1, indicating that LKB1 may play a crucial role by phosphorylating SIK1 at Thr182, possibly as an initiator of the autophosphorylation cascade, and GSK-3beta may phosphorylate SIK1 at Thr182 by recognizing the priming-autophosphorylation at Ser186 in cultured cells.	SIGNOR-279742
P05981	P08709	1	cleavage	up-regulates activity	0.347	Hepsin, a putative membrane-associated serine protease, activates human factor VII and initiates a pathway of blood coagulation on the cell surface leading to thrombin formation\|In contrast, an activation cleavage site factor VII mutant, R152E factor VII, was not cleaved by hepsin-transfected cells, suggesting that factor VII and S344A factor VII were activated on these cells by cleavage of the Arg152-Ile153 peptide bond. I	SIGNOR-263638
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
P10636	P05186	0	dephosphorylation	down-regulates activity	0.2	TNAP dephosphorylates overphosphorylated tau once it is released upon neuronal death.	SIGNOR-277097
Q92934	P31749	0	phosphorylation	down-regulates activity	0.823	Experiments in this study reveal that akt phosphorylates bad both in vitro and in vivo and that akt-mediated phosphorylation of bad effectively blocks bad induced cell death.[...] In addition, these findings implicate a particular phosphorylation site on bad, serine 136, in the suppression of bad-mediated death by akt.[...]The Phosphorylation of bad may lead to the prevention of cell death via a mechanism that involves the selective association of the phosphorylated forms of bad with 14-3-3 protein isoforms. Akt phosphorylates bad in vitro and in vivo we show that growth factor activation of the pi3'k/akt signaling pathway culminates in the phosphorylation of the bcl-2 family member bad, thereby suppressing apoptosis and promoting cell survival. Akt phosphorylates bad in vitro and in vivo erbb-mediated phosphorylation of bad by akt promotes survival by blocking the interaction of this pro-apoptotic molecule with bcl-2 and bcl-x proteins	SIGNOR-52863
P16220	O75582	0	phosphorylation	up-regulates	0.731	Msk1 is localized in the nucleus of unstimulated or stimulated cells, and phosphorylates creb at ser133_ .MSK1 Is activated in vitro by mapk2/erk2 or sapk2/p38. Endogenous msk1 is activated in 293 cells by either growth factor/phorbol ester stimulation, or by exposure to uv radiation, and oxidative and chemical stres msk was the kinase responsible for phosphorylation of the transcription factor creb in response to tcr stimulation. Pka, ca2+-calmodulin-dependent kinase iv (camkiv), msk, p70s6k and rsk phosphorylate creb.	SIGNOR-59458
P50750	P36873	0	dephosphorylation	up-regulates	0.2	Pp1 is an activator of cdk9. Pp1 dephosphorylates cdk9 thr186.	SIGNOR-173454
P46934	Q96NT3	1	polyubiquitination	down-regulates quantity by destabilization	0.419	The E3 ligase NEDD4 regulates GUCD1 degradation. many polyubiquitinylated species of GUCD1 appeared as high molecular weight forms, suggesting that GUCD1 is degraded by the proteasome, after polyubiquitin chain formation, in the presence of NEDD4-1.	SIGNOR-272846
P18031	P08922	1	dephosphorylation	down-regulates	0.374	In an approach to gain insight into the sequence-dependent dephosphorylation of multiple phosphotyrosyl-containing peptides by the phosphatases shp-1 and ptp1b, we applied a chromatographic technique for the analysis of the dephosphorylation products.	SIGNOR-154199
P61586	Q92502	0	gtpase-activating protein	down-regulates activity	0.557	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-260519
Q9UJD0	P20336	1	relocalization	up-regulates activity	0.282	N-terminal interactions of RIMs with RAB3 and MUNC13 regulate DCV fusion. Through N-terminal interactions, RIMs position MUNC13 and recruit DCVs via RAB3, which is located on the vesicle	SIGNOR-264379
P14618	P40763	1	phosphorylation	up-regulates activity	0.443	PKM2 activates transcription of MEK5 by phosphorylating stat3 at Y705. In vitro phosphorylation assays show that PKM2 is a protein kinase using PEP as a phosphate donor	SIGNOR-267716
P04114	O60216	0	transcriptional regulation	down-regulates quantity	0.2	The promoter region of APOB bound RAD21 but not RAD21 p.622 Ala>Thr; expression of wild-type RAD21 in HEK293 cells repressed expression of APOB, compared with control vector.	SIGNOR-259974
P16949	Q9UQM7	0	phosphorylation	down-regulates	0.403	Involved in the regulation of the microtubule (mt) filament system by destabilizing microtubules. Prevents assembly and promotes disassembly of microtubules. In vitro, ser16 of recombinant human stathmin was phosphorylated also by purified cam kinase ii, and in vivo, cam kinase ii activity was indeed stimulated in cd2-triggered jurkat cells. Altogether, our results favor an association of cam kinase ii activity with costimulatory signals of t lymphocyte activation and phosphorylation of stathmin on ser16.	SIGNOR-149640
Q13887	Q14258	0	polyubiquitination	down-regulates quantity by destabilization	0.482	The oestrogen-inducible E3 ligase EFP (oestrogen-responsive finger protein) was identified as a key player in oestrogen-mediated degradation of KLF5, as knockdown and overexpression of EFP increased and decreased KLF5 protein levels respectively, and the decrease continued even when protein synthesis was blocked.	SIGNOR-271908
O15111	Q9Y243	0	phosphorylation	up-regulates	0.414	Although there are likely to be multiple levels of crosstalk between the pi3k-akt and nf-kb pathways, one mechanism has been attributed to direct phosphorylation of the amino acid residue t23 on ikb kinase alfa (ikkalfa) by akt, thereby leading to activation of this kinase upstream of nf-kb akt mediates ikkalpha phosphorylation at threonine 23 akt transiently associates in vivo with ikk and induces ikk activation. Akt mediates ikkalfa phosphorylation at threonine 23.Akt phosphorylates ikkalpha on t23, and this phosphorylation event is a prerequisite for the phosphorylation of p65 at s534 by ikkalpha and beta	SIGNOR-187062
Q16539	O60381	1	phosphorylation	up-regulates	0.43	A mutation of the p38 map kinase phosphorylation site at aa 401 [(s-a)401hbp1] also triggered hbp1 protein instability. While protein stability was compromised by mutation, the specific activities of (s-a)401hbp1 and of wild-type hbp1 appeared comparable for transcriptional repression.	SIGNOR-119138
Q13043	P42574	0	cleavage	up-regulates activity	0.617	In response to apoptotic stimuli, caspase cleavage of mst1 occurs at asp-326 and asp-349, resulting in the separation of its n-terminal kinase domain from the nes-containing c-terminal domain. Thus, caspase cleavage of mst1 serves two purposes: one is activation of mst1 kinase activity and the other is translocation of mst1 into the nucleus.	SIGNOR-109878
P54252	P68400	0	phosphorylation	up-regulates activity	0.2	Here we show that protein casein kinase 2 (CK2)-dependent phosphorylation controls the nuclear localization, aggregation and stability of ataxin-3 (ATXN3), the disease protein in spinocerebellar ataxia type 3 (SCA3). The main phosphorylation of ATXN3 in vivo thus occurred at serine residues within the three conserved UIMs.	SIGNOR-276224
P49674	Q13541	1	phosphorylation	down-regulates	0.2	Mechanistic investigations showed that ck1_ interacted with and phosphorylated 4e-bp1 at two novel sites t41 and t50, which were essential for 4e-bp1 inactivation along with increased mrna translation and cell proliferation.	SIGNOR-203240
O75449	Q92630	0	phosphorylation	down-regulates quantity by destabilization	0.509	DYRK2 mediated phosphorylation is required for Katanin p60 degradation. Serine 42, serine 109 and threonine 133 are likely to be the major DYRK2 phosphorylation sites as single mutations for these sites showed reduced phosphorylation by DYRK2 and the triple mutant showed almost no DYRK2 mediated phosphorylation (Fig. 5d).	SIGNOR-262847
P50750	P49459	1	phosphorylation	up-regulates activity	0.449	CDK9 phosphorylates RNA polymerase II CTD at serine 2 to recruit the RNF20/40 E3 ubiquitin ligase, which is required for H2Bub1, and phosphorylates UBE2A at serine 120 to increase its activity in regulating H2Bub1.	SIGNOR-279025
P84243	P29375	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-264301
P42574	Q13464	1	cleavage	up-regulates	0.734	Rock i is cleaved by casp3 at a conserved detd1113/g sequence and its carboxy-terminal inhibitory domain is removed, resulting in deregulated and constitutive kinase activity.	SIGNOR-106546
P50613	Q01860	1	phosphorylation	up-regulates quantity by stabilization	0.2	Here, we combined molecular and cellular biology with CRISPR/Cas9-mediated genome engineering to pinpoint the function of serine 12 of OCT4 in ESCs. Using chemical inhibitors and an antibody specific to OCT4 phosphorylated on S12, we identified cyclin-dependent kinase (CDK) 7 as upstream kinase. \|Phosphorylation of OCT4 on S12 has been previously implicated to stabilize OCT4 by binding to PIN1, thereby preventing ubiquitinylation by WWP2.	SIGNOR-264404
Q00535	O60331	1	phosphorylation	down-regulates	0.364	The interaction of talin with phosphatidylinositol(4) phosphate 5 kinase type i gamma (pipki gamma) regulates pi(4,5)p2 synthesis at synapses and at focal adhesions. Here, we show that phosphorylation of serine 650 (s650) within the talin-binding sequence of human pipki gamma blocks this interaction. At synapses, s650 is phosphorylated by p35/cdk5 and mitogen-activated protein kinase at rest, and dephosphorylated by calcineurin upon stimulation.	SIGNOR-134455
O15294	P49841	0	phosphorylation	up-regulates activity	0.518	But OGT activity is modulated by GSK3beta (XREF_FIG) and GSK3beta activity is known to oscillate through Ser9 phoshorylation.\|Here, we found that OGT is phosphorylated at serines 3 or 4 by GSK3beta and that O GlcNAcylation of OGT also occurs on the same or neighboring serine residues, suggesting interacting phosphorylation and O GlcNAcylation events on OGT itself.	SIGNOR-279528
P63000	Q7Z6I6	0	gtpase-activating protein	down-regulates activity	0.403	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-260486
P12931	P19367	1	phosphorylation	down-regulates activity	0.492	Mechanistically, c-Src phosphorylation of HK1 at Tyr732 robustly decreases its K m and increases its V max by disrupting its dimer formation.\|Mechanistically, c-Src-mediated Y732 phosphorylation disrupts HK1 dimer formation, alters its enzyme kinetics and eventually enhances enzymatic activity ( ).	SIGNOR-278209
O14757	Q7Z2Z1	1	phosphorylation	down-regulates activity	0.432	In principle, phosphorylation of Treslin by Chk1 may alter its conformation or directly affect its interactions with other proteins to preclude helicase activation.\|The fact that the TRCT domain blocks the binding of Chk1 to Treslin suggests that Chk1 suppresses the initiating function of Treslin.	SIGNOR-278924
P08575	P68400	0	phosphorylation	up-regulates	0.442	Mutational analysis of ck2 consensus sites showed that the target for ck2 was in an acidic insert of 19 amino acids in the d2 domain, and ser to ala mutations at amino acids 965, 968, 969, and 973 abrogated ck2 phosphorylation of cd45. Ck2 phosphorylation increased cd45 activity 3-fold toward phosphorylated myelin basic protein,	SIGNOR-65277
Q02363	Q9Y463	0	phosphorylation	down-regulates activity	0.2	Phosphorylation of Thr27 of ID2 by DYRK1 blocks ID2-VHL interaction and preserves HIF2Œ± ubiquitylation.\|We report that DYRK1A and DYRK1B kinases phosphorylate ID2 on Threonine-27 (T27).	SIGNOR-279033
P17612	Q9UQL6	1	phosphorylation	up-regulates activity	0.2	PKA/Cdk5-mediated phosphorylation of HDAC5 at Ser279 within the NLS promotes nuclear localization of HDAC5 and interaction with the nuclear corepressor complex	SIGNOR-198658
Q8IXJ6	P15172	1	deacetylation	down-regulates	0.376	Sir2-mediated deacetylation of myod can be expected to inhibit its transcriptional capabilities.	SIGNOR-104251
P16949	O14965	0	phosphorylation	down-regulates activity	0.388	Inhibition of AURKA activity activates stathmin function via reduced phosphorylation and facilitates microtubule destabilization in RB1 -/- cells, heavily impacting the bipolar spindle formation and inducing mitotic cell death selectively in RB1 -/- cells.\|Two serine phosphorylation sites, Ser16 and Ser63, in stathmin contain a consensus sequence for AURKA phosphorylation and the mutations in these two serine sites abolished stathmin phosphorylation by AURKA, suggesting that stathmin is a substrate of AURKA for phosphorylation xref , xref .	SIGNOR-278913
P19634	Q16539	0	phosphorylation	up-regulates	0.571	Trophic factor withdrawal: p38 mitogen-activated protein kinase activates nhe1, which induces intracellular alkalinization. activated p38 mapk directly phosphorylated the c terminus of nhe1 within a 40-amino-acid region. Analysis by mass spectroscopy identified four phosphorylation sites on nhe1, thr 717, ser 722, ser 725, and ser 728.	SIGNOR-111043
P10415	Q16539	0	phosphorylation	down-regulates activity	0.334	Bcl-2 phosphorylation by p38 mapkin this study, we identify, by using mass spectrometry techniques and specific anti-phosphopeptide antibodies, ser(87) and thr(56) as the bcl-2 residues phosphorylated by p38 mapk and show that phosphorylation of these residues is always associated with a decrease in the antiapoptotic potential of bcl-2 protein.	SIGNOR-146786
Q00987	Q92831	1	ubiquitination	down-regulates quantity by destabilization	0.621	Consistently, overexpression of MDM2 in p53 null cells caused the reduction of the protein level of PCAF, but not the mRNA level.\|MDM2 ubiquitinated PCAF in vitro and in cells.	SIGNOR-278825
Q15796	Q13233	0	phosphorylation	up-regulates activity	0.474	As yet, the apparent discrepancy between these and above data is not clear, but obviously the type of cell under study and the cellular context may play an important role.In endothelial cells, Smad2 activity is stimulated by MEKK1, a component of the Stress Activated Protein Kinase and c-Jun N terminal kinase (SAPK and JNK) pathway.\|Phosphorylation of Smad2 by MEKK1 increased its association with Smad4, its nuclear accumulation and its transcription induction activity .	SIGNOR-279064
Q14940	P49407	0	relocalization	down-regulates activity	0.401	Internalization of the Na(+)/H(+) exchanger NHE5 into recycling endosomes is enhanced by the endocytic adaptor proteins beta-arrestin1 and -2, best known for their preferential recognition of ligand-activated G protein-coupled receptors (GPCRs)	SIGNOR-275505
P10636	Q9BXM7	0	phosphorylation	down-regulates activity	0.384	Simultaneously overexpressing PINK1 significantly reduced the levels of exogenous total and phosphorylated tau proteins (Figures 4A,B,E).\|Taken together, our data revealed that PINK1 overexpression promoted degradation of abnormal accumulated tau via the autophagy-lysosome pathway, indicating that PINK1 may be a potential target for AD treatment.	SIGNOR-279250
Q86Y07	Q13469	1	phosphorylation	up-regulates	0.369	We demonstrate that vrk2 directly interacts and phosphorylates nfat1 in ser-32 within its n-terminal transactivation domain.	SIGNOR-199263
P30281	P62136	0	dephosphorylation	up-regulates	0.246	These results support the hypothesis that pp1 constitutively keeps cyclin d3 in a stable, dephosphorylated state	SIGNOR-142884
P27361	P01106	1	phosphorylation	up-regulates activity	0.707	ERK1 phosphorylates MYC Ser62 resulting in MYC stabilization and activation	SIGNOR-236250
P11532	Q12955	0	relocalization	up-regulates quantity	0.367	We present evidence for an ankyrin-based mechanism for sarcolemmal localization of dystrophin and beta-DG. Ankyrin-B thus is an adaptor required for sarcolemmal localization of dystrophin, as well as dynactin-4.	SIGNOR-266715
P14923	Q9UI47	0	relocalization	up-regulates quantity	0.484	Overexpression of CTNNA3 in a CTNNA1 negative colon carcinoma cell line resulted in the reassembly of the adherens and tight junctions through the recruitment of CTNNA3 interacting partners such as E-cadherin, β-catenin, plakoglobin, and ZO-14	SIGNOR-265494
O00206	P12931	0	phosphorylation	up-regulates activity	0.588	Src dependent phosphorylation of TLR4 is significantly increased in Cftr-KO cholangiocytes.\|TLR4 can be activated through the phosphorylation of its TIR domains by Src, a non receptor tyrosine kinase 28.	SIGNOR-279658
Q15139	P27986	1	phosphorylation	up-regulates activity	0.2	PKD1 phosphorylates p85α to enhance its interaction with PTEN, leading to polarized PTEN activity, thereby regulating neutrophil migration.	SIGNOR-276426
P78527	P42575	1	phosphorylation	up-regulates	0.297	Here we show that dna damage induced by gamma-radiation triggers the phosphorylation of nuclear caspase-2 at the s122 site within its prodomain, leading to its cleavage and activation. This phosphorylation is carried out by the nuclear serine/threonine protein kinase dna-pkcs	SIGNOR-183895
Q15131	P15036	1	phosphorylation	down-regulates quantity by destabilization	0.528	Altogether, these results suggest that CDK10/cyclin M directly controls ETS2 degradation through the phosphorylation of these two serines.	SIGNOR-260914
Q13464	Q14457	1	phosphorylation	up-regulates activity	0.415	Beclin1 is phosphorylated by ROCK1 at T119.	SIGNOR-278198
Q99558	O14920	1	phosphorylation	up-regulates	0.714	Activation of the transcription factor nf-kappab by inflammatory cytokines involves the successive action of nf-kappab-inducing kinase (nik) and two ikappab kinases, ikk-alpha and ikk-beta. Here we show that nik preferentially phosphorylates ikk-alpha over ikk-beta	SIGNOR-55949
P27361	Q9BZI1	1	phosphorylation	up-regulates activity	0.2	To identify the phosphorylated residue, we introduced a serine-to-alanine substitution at residues 294 and 326 and a threonine-to-alanine substitution at residue 331 in Irx2(291–356). Erk1 phosphorylated S294A and T331A, but not S326A (Fig. 4b), indicating that Ser326 is the bona fide MAP kinase target.	SIGNOR-263061
Q68D86	P51955	0	phosphorylation	down-regulates activity	0.2	CCDC102B is recruited to the centrosome by C-Nap1 (also known as CEP250) and interacts with the centrosome linker components rootletin and LRRC45. CCDC102B decorates and facilitates the formation of rootletin filaments. Furthermore, CCDC102B is phosphorylated by Nek2A (an isoform encoded by NEK2) and is disassociated from the centrosome at the onset of mitosis.	SIGNOR-275626
P49841	P20929	1	phosphorylation	down-regulates	0.306	Gsk3b is able to phosphorylate nebulin at two ser sites in the c-terminal region of nebulin localized to the z-disk, thus preventing the interaction of nebulin with neuronal wiscott-aldrich syndrome protein (nwasp), a ubiquitously expressed member of the wasp family, which is involved in actin assembly.	SIGNOR-175659
P17677	Q6UB99	0	transcriptional regulation	up-regulates quantity by expression	0.2	Neurite growth-related genes such as Trkb, Bdnf, Gap43, Coronin 1B, and Rab13 are downregulated in ANKRD11-deficient neurons.	SIGNOR-266736
P98170	O43353	1	ubiquitination	up-regulates activity	0.628	XIAP is the essential E3 for RIPK2 ubiquitination and interacts with RIPK2 through its baculoviral IAP-repeat (BIR).	SIGNOR-280449
Q8IYT8	P06733	1	phosphorylation	down-regulates activity	0.2	Here, we demonstrate that, during deprivation of amino acid and growth factors, ULK1/2 directly phosphorylate key glycolytic enzymes including hexokinase (HK), phosphofructokinase 1 (PFK1), enolase 1 (ENO1), and the gluconeogenic enzyme fructose-1,6-bisphosphatase (FBP1).Phosphorylation of these enzymes leads to enhanced HK activity to sustain glucose uptake but reduced activity of FBP1 to block the gluconeogenic route and reduced activity of PFK1 and ENO1 to moderate drop of glucose-6-phosphate and to repartition more carbon flux to pentose phosphate pathway (PPP), maintaining cellular energy and redox homeostasis at cellular and organismal levels.Similar results were also obtained using ULK2 as the kinase (data not shown).	SIGNOR-274037
Q13153	P03372	1	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
O15503	Q9UKV5	0	ubiquitination	down-regulates quantity by destabilization	0.525	The ubiquitination of Insig-1 is mediated by gp78 and regulated by sterols.\|gp78 mediates the degradation of Insig-1 and Insig-2.	SIGNOR-278567
Q96FF9	P53350	0	phosphorylation	down-regulates activity	0.705	Here we show that the mitotic kinases Aurora B and Cyclin-dependent kinase 1 (Cdk1) destabilize interactions between Sororin and the cohesin subunit precocious dissociation of sisters protein 5 (Pds5) by phosphorylating Sororin, leading to release of acetylated cohesin from chromosome arms and loss of cohesion.	SIGNOR-276122
P12931	Q16832	1	phosphorylation	up-regulates	0.38	Here, using baculoviral co-expression of the ddr2 cytosolic domain and src, we show that src targets three tyrosine residues (tyr-736, tyr-740, and tyr-741) in the activation loop of ddr2 for phosphorylation. This phosphorylation by src stimulates ddr2 cis-autophosphorylation of additional tyrosine residues.	SIGNOR-140767
P46934	Q9NV92	0	relocalization	down-regulates activity	0.568	Ndfip1 is primarily localized in the Golgi apparatus where it recruits Nedd4-2 to mediate the degradation of mature hERG proteins during channel trafficking to the plasma membrane. Although Ndfip2 directs Nedd4-2 to the Golgi apparatus, it also recruits Nedd4-2 to the multivesicular bodies (MVBs), which may impair MVB function and impede the degradation of mature hERG proteins mediated by Nedd4-2.	SIGNOR-260995
O95613	Q76N32	0	relocalization	up-regulates activity	0.34	We also found that Cep68 forms a complex with Cep215 (also known as Cdk5Rap2) and PCNT (also known as pericentrin), two PCM (pericentriolar material) proteins involved in centriole engagement. \|Cep68 stabilization increases the amount of PCNT at metaphase centrosomes, but does not affect its removal at the end of mitosis	SIGNOR-275623
P21399	P17252	0	phosphorylation	down-regulates	0.2	Irp1 ser-711 is a phosphorylation site, critical for regulation of rna-binding and aconitase activities.	SIGNOR-133188
Q99612	P18847	1	transcriptional regulation	up-regulates quantity by expression	0.394	KLF6 binds directly to and activates the ATF3 promoter.	SIGNOR-266051
P06493	Q9UNH5	1	phosphorylation	up-regulates activity	0.54	We found that Cdc14A is phosphorylated on Ser411, Ser453 and Ser549 by Cdk1 early in mitosis and becomes dephosphorylated during late mitotic stages.	SIGNOR-278264
Q96GD4	Q69YH5	1	phosphorylation	down-regulates activity	0.446	This result demonstrates that the three sites of Repo-Man (Ser-543, Ser-977, and Ser-981) are phosphorylated by Aurora B in early mitosis. We uncover that PP1γ is recruited to mitotic chromosomes by its regulatory subunit Repo-Man in the absence of Aurora B activity and that Aurora B regulates dissociation of PP1γ by phosphorylating and disrupting PP1γ-Repo-Man interactions on chromatin.	SIGNOR-274001
P68871	P19338	0	post transcriptional regulation	up-regulates quantity by expression	0.2	Nucleolin binds human β-globin mRNA. A Nucleolin-Binding 3′ Untranslated Region Element Stabilizes β-Globin mRNA In Vivo	SIGNOR-251844
Q9Y463	Q9UKV0	1	phosphorylation	down-regulates	0.2	Mirk activated mef2 not through direct phosphorylation of mef2 but by phosphorylation of its inhibitors, the class ii histone deacetylases (hdacs). Mef2 is sequestered by class ii hdacs such as hdac5 and mef2-interacting transcriptional repressor (mitr). Mirk antagonized the inhibition of mef2c by mitr, whereas kinase-inactive mirk was ineffective. Mirk phosphorylates class ii hdacs at a conserved site within the nuclear localization region, reducing their nuclear accumulation in a dose-dependent and kinase-dependent manner	SIGNOR-235813
P63000	Q96HP0	0	guanine nucleotide exchange factor	up-regulates activity	0.528	Dock6 is a guanine nucleotide exchange factor (GEF) that activates the Rho family guanosine triphosphatases Rac1 and Cdc42 to regulate the actin cytoskeleton.	SIGNOR-275670
Q02078	Q9UKX2	1	transcriptional regulation	up-regulates quantity by expression	0.325	Myocyte enhancer factor-2 and serum response factor binding elements regulate fast Myosin heavy chain transcription in vivo. We show that the upstream promoter region of the gene most abundantly expressed in mouse skeletal muscles, IIb MyHC, retains binding activity and transcriptional activation for three positive transcription factors, the serum response factor, Oct-1, and myocyte enhancer factor-2, whereas the other two genes (IIa and IId/x) have nucleotide substitutions in these sites that reduce binding and transcriptional activation	SIGNOR-238703
Q92830	P0DPK5	1	acetylation	down-regulates activity	0.2	The HAT module within the SAGA and ADA complexes acetylates histone H3, mainly on residues K9 and K14.	SIGNOR-269598
O00750	P00533	0	phosphorylation	up-regulates	0.44	The n-terminal region of pi3k-c2beta was found to selectively interact with the egf receptor in vitro, suggesting that it mediates the association of this pi3k with the receptor.	SIGNOR-77195
Q14938	Q02535	1	transcriptional regulation	down-regulates quantity	0.2	By integrating transcriptomic profiling (RNA-seq) of Nfia- and Nfix-deficient GNPs with epigenomic profiling (ChIP-seq against NFIA, NFIB and NFIX, and DNase I hypersensitivity assays), we reveal that these transcription factors share a large set of potential transcriptional targets, suggestive of complementary roles for these NFI family members in promoting neural development	SIGNOR-268885
Q14721	P18433	0	dephosphorylation	down-regulates	0.2	Ptpalpha inhibits kv channels more strongly than ptpepsilon;this correlates with constitutive association of ptpalpha with kv2.1, driven by membranal localization of ptpalpha.	SIGNOR-148301
P24941	O43303	1	phosphorylation	down-regulates activity	0.515	GST-tagged recombinant CP110 (GST-wt) was robustly phosphorylated by cyclin E/CDK2 (Figure 2A). Expression of a mutant derivative of CP110 refractory to CDK phosphorylation provokes marked polyploidy. We localized the majority (nine of ten) of potential CDK2 phosphorylation sites in CP110 to an amino-terminal fragment (GST-ΔN1; Figure 1B)	SIGNOR-265956
P06241	P12318	1	phosphorylation	up-regulates activity	0.534	To identify the FcgammaRII-phosphorylating protein tyrosine kinase (PTK), we used the combination of an in vitro and an in vivo approach. In an in vitro assay using recombinant cytoplasmic tails of the different FcgammaRII isoforms as well as tyrosine exchange mutants, we show that each of the BCR-associated PTKs (Lyn, Blk, Fyn, and Syk) shows different phosphorylation patterns with regard to the different FcgammaR isoforms and point\|Fyn and Blk definitely phosphorylate Y-282 in the ITAM of Fc_RIIa/c, whereas the non-ITAM tyrosine residue (Y-275) becomes phosphorylated by Syk, as the phosphorylation of double point mutants shows. In addi-tion to these tyrosine residues, Fyn, Blk, and Syk might phosphorylate the most C-terminal tyrosine residue (Y-298) because altering this tyrosine residue together with one of the tyrosine residues clearly shown to be phosphorylated by the respective PTK results in the abrogation of phosphorylation.	SIGNOR-249336
P49841	Q9UBN7	1	phosphorylation	up-regulates activity	0.381	GSK3beta was found to co-localize with HDAC6 in hippocampal neurons, and inhibition of GSK3beta resulted in decreased binding of antibody to phosphoserine-22, a potential GSK3beta phosphorylation site in HDAC6.\|This suggests that GSK3\u03b2 may directly phosphorylate HDAC6 at this site, although further work with purified proteins is needed to determine whether this is the case.\|The fact that HDAC6 is the predominant cytoplasmic deacetylase in neurons suggests that GSK3beta dependent phosphorylation may enhance HDAC6 activity, resulting in a decrease in acetylation of tubulin and an inhibition of both mitochondrial motility and the transport of other kinesin-1 dependent cargoes.	SIGNOR-278941
P45983	P15336	1	phosphorylation	up-regulates	0.78	Activating transcription factor-2 (atf2) was found to be a target of the jnk signal transduction pathway. Atf2 was phosphorylated by jnk on two closely spaced threonine residues within the nh2-terminal activation domain.	SIGNOR-33914
P00519	Q8N2M8	1	phosphorylation	up-regulates activity	0.2	In biochemical assays and in Xenopus growth cones we find that Abl kinase activity enhances the association or co-localization of CLASP2 and F-actin, consistent with previous reports of CLASP binding to actin [Tsvetkov et al., ].\|In vitro, Abl phosphorylates CLASP with a Km of 1.89 \u00b5M, indicating that CLASP is a bona fide substrate.	SIGNOR-280166
Q15797	Q9P0J1	0	dephosphorylation	down-regulates	0.243	We show that the mammalian pdps are important in dephosphorylation of bmp-activated smad1 but not tgf-beta-activated smad2 or smad3. Thus, pdps specifically inactivate smads in the bmp/dpp pathway. [...] These observations suggest that pdp1 and pdp2 are important for dephosphorylation of smad1.	SIGNOR-144876
P38117	Q8IXQ9	0	methylation	down-regulates activity	0.2	Accordingly, we found that METTL20-mediated methylation of ETFβ in vitro reduced its ability to receive electrons from the medium chain acyl-CoA dehydrogenase and the glutaryl-CoA dehydrogenase. In conclusion, the present study establishes METTL20 as the first human KMT localized to mitochondria and suggests that it may regulate cellular metabolism through modulating the interaction between its substrate ETFβ and dehydrogenases.	SIGNOR-269450

P07948

P19174

1

phosphorylation

up-regulates activity

0.656

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

SIGNOR-249381

O95239

P53350

0

phosphorylation

down-regulates activity

0.467

Moreover, phosphorylation of KIF4 and condensin I by Aurora B and polo like kinase 1 (Plk1) is important for KIF4 and condensin I localization to the chromosome.|These results suggest that Plk1 negatively regulates the loading of both KIF4 and condensin to the chromosome.

SIGNOR-280069

P29350

P63261

1

dephosphorylation

down-regulates

0.2

Our data suggest that shp-1 plays a pivotal role in reorganization of cytoskeletal architecture inducing actin dephosphorylation. These results clearly demonstrate the direct interaction of shp-1 with actin

SIGNOR-99565

P06493

Q8NFH5

1

phosphorylation

down-regulates activity

0.563

Collectively, these data show that mitotic hyperphosphorylation of Nup53 by CDK1 and PLK1 contributes to its removal from NPCs.|The combined mutation of the CDK1 and PLK1 sites to phosphomimetic residues almost completely abolished NPC integration of Nup53, indicating that hyperphosphorylation of Nup53 might be incompatible with its NPC association.

SIGNOR-278917

Q9UQ26

P20336

1

relocalization

up-regulates activity

0.762

N-terminal interactions of RIMs with RAB3 and MUNC13 regulate DCV fusion. Through N-terminal interactions, RIMs position MUNC13 and recruit DCVs via RAB3, which is located on the vesicle

SIGNOR-264377

Q92626

Q16236

0

transcriptional regulation

up-regulates quantity by expression

0.2

PXDN expression in response to H2O2 and the Nrf2-specific inducers, tert-butylhydroquinone (tBHQ) and sulforaphane (SFN), was determined by western blotting and immunofluorescence microscopy, in HeLa and HEK293 cells.We found that Nrf2 binds to and increases luciferase reporter gene expression from the PXDN promoter via a putative Nrf2-binding site. In summary, we show that PXDN is a novel target of the redox sensitive transcription factor Nrf2.

SIGNOR-265248

O14640

Q9NQ66

1

null

up-regulates activity

0.275

Dsh through PLC activates IP3, which leads to release of intracellular Ca2+, which in turn activates CamK11 and calcineurin

SIGNOR-258978

Q13546

Q96AX9

0

ubiquitination

down-regulates quantity by destabilization

0.295

These data suggest that after binding, MIB2 inhibits RIPK1 through a mechanism that is dependent on the E3 ligase activity of MIB2.|Whereas MIB2 readily ubiquitylated wild-type RIPK1, mutating K377 to R significantly reduced MIB2 mediated ubiquitylation of RIPK1 (XREF_SUPPLEMENTARY A).

SIGNOR-278633

Q05D32

Q8TDR2

1

dephosphorylation

up-regulates quantity by stabilization

0.282

We found that peptides corresponding to phosphoserines 194 and 216 of PDIK1L (S385 and S413 of STK35) were efficiently dephosphorylated by SCP4, whereas no activity was detected for the other two phosphopeptides (Figure 6D).

SIGNOR-273775

P17252

P35612

1

phosphorylation

down-regulates

0.2

We now demonstrate that ptn stimulates the phosphorylation of serines 713 and 726 in the myristoylated alanine-rich protein kinase (pk) c substrate domain of beta-adducin through activation of either pkc alpha or beta.

SIGNOR-139870

Q14586

P09238

1

transcriptional regulation

down-regulates quantity by repression

0.39

Furthermore, ZNF267 binds to the MMP-10 promoter region as demonstrated by chromatin immunoprecipitation assays. In conclusion, our results suggest that ZNF267 as a negative transcriptional regulator of MMP-10

SIGNOR-266211

P27361

Q14934

1

phosphorylation

up-regulates

0.289

The formation of rsk-nfatc4-dna transcription complex is also apparent upon adipogenesis. Bound rsk phosphorylates ser(676) and potentiates nfatc4 dna binding by escalating nfat-dna association. Ser(676) is also targeted by the erk map kinase, which interacts with nfat at a distinct region than rsk. Thus, integration of the erk/rsk signaling pathway provides a mechanism to modulate nfatc4 transcription activity.

SIGNOR-133276

P04637

O95155

0

polyubiquitination

down-regulates quantity by destabilization

0.396

We show that ubiquitination factor E4B (UBE4B), an E3 and E4 ubiquitin ligase, physically interacts with p53 and Hdm2 (also known as Mdm2 in mice). UBE4B promotes p53 polyubiquitination and degradation and inhibits p53-dependent transactivation and apoptosis.

SIGNOR-271907

P61586

Q86VW2

0

guanine nucleotide exchange factor

up-regulates activity

0.835

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-260544

Q04759

P32942

1

phosphorylation

up-regulates activity

0.334

Ser489 was a phosphorylation site in vitro for recombinant protein kinase Ctheta. Finally, treatment of Jurkat cells with chelerythrine chloride, a protein kinase C inhibitor, prevented ICAM-3-triggered spreading.

SIGNOR-248979

P49841

P10275

1

phosphorylation

down-regulates activity

0.649

Glycogen synthase kinase-3 beta is involved in the phosphorylation and suppression of androgen receptor activity.|In particular, we showed that glycogen synthase kinase-3 beta phosphorylates the androgen receptor, thereby inhibiting androgen receptor-driven transcription.

SIGNOR-279334

Q4VCS5

P46937

1

relocalization

down-regulates

0.734

Yap/taz and angiomotin (amot) family proteins were shown to interact, resulting in yap/taz localization to tight junctions and inhibition through phosphorylation-dependent and -independent mechanisms.

SIGNOR-175779

P57059

P49841

0

phosphorylation

up-regulates activity

0.2

Glycogen synthase kinase-3beta (GSK-3beta) phosphorylates Ser/Thr residues located at the fourth position ahead of the pre-phosphorylated Ser/Thr residues, and inhibitors of GSK-3beta reduce the phosphorylation at Thr182. The results of an in vitro reconstitution assay also indicate that GSK-3beta could be the SIK1 kinase. However, overexpression and knockdown of GSK-3beta in LKB1-defective HeLa cells suggests that GSK-3beta alone may not be able to phosphorylate or activate SIK1, indicating that LKB1 may play a crucial role by phosphorylating SIK1 at Thr182, possibly as an initiator of the autophosphorylation cascade, and GSK-3beta may phosphorylate SIK1 at Thr182 by recognizing the priming-autophosphorylation at Ser186 in cultured cells.

SIGNOR-279742

P05981

P08709

1

cleavage

up-regulates activity

0.347

Hepsin, a putative membrane-associated serine protease, activates human factor VII and initiates a pathway of blood coagulation on the cell surface leading to thrombin formation|In contrast, an activation cleavage site factor VII mutant, R152E factor VII, was not cleaved by hepsin-transfected cells, suggesting that factor VII and S344A factor VII were activated on these cells by cleavage of the Arg152-Ile153 peptide bond. I

SIGNOR-263638

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

P10636

P05186

0

dephosphorylation

down-regulates activity

0.2

TNAP dephosphorylates overphosphorylated tau once it is released upon neuronal death.

SIGNOR-277097

Q92934

P31749

0

phosphorylation

down-regulates activity

0.823

Experiments in this study reveal that akt phosphorylates bad both in vitro and in vivo and that akt-mediated phosphorylation of bad effectively blocks bad induced cell death.[...] In addition, these findings implicate a particular phosphorylation site on bad, serine 136, in the suppression of bad-mediated death by akt.[...]The Phosphorylation of bad may lead to the prevention of cell death via a mechanism that involves the selective association of the phosphorylated forms of bad with 14-3-3 protein isoforms. Akt phosphorylates bad in vitro and in vivo we show that growth factor activation of the pi3'k/akt signaling pathway culminates in the phosphorylation of the bcl-2 family member bad, thereby suppressing apoptosis and promoting cell survival. Akt phosphorylates bad in vitro and in vivo erbb-mediated phosphorylation of bad by akt promotes survival by blocking the interaction of this pro-apoptotic molecule with bcl-2 and bcl-x proteins

SIGNOR-52863

P16220

O75582

0

phosphorylation

up-regulates

0.731

Msk1 is localized in the nucleus of unstimulated or stimulated cells, and phosphorylates creb at ser133_ .MSK1 Is activated in vitro by mapk2/erk2 or sapk2/p38. Endogenous msk1 is activated in 293 cells by either growth factor/phorbol ester stimulation, or by exposure to uv radiation, and oxidative and chemical stres msk was the kinase responsible for phosphorylation of the transcription factor creb in response to tcr stimulation. Pka, ca2+-calmodulin-dependent kinase iv (camkiv), msk, p70s6k and rsk phosphorylate creb.

SIGNOR-59458

P50750

P36873

0

dephosphorylation

up-regulates

0.2

Pp1 is an activator of cdk9. Pp1 dephosphorylates cdk9 thr186.

SIGNOR-173454

P46934

Q96NT3

1

polyubiquitination

down-regulates quantity by destabilization

0.419

The E3 ligase NEDD4 regulates GUCD1 degradation. many polyubiquitinylated species of GUCD1 appeared as high molecular weight forms, suggesting that GUCD1 is degraded by the proteasome, after polyubiquitin chain formation, in the presence of NEDD4-1.

SIGNOR-272846

P18031

P08922

1

dephosphorylation

down-regulates

0.374

In an approach to gain insight into the sequence-dependent dephosphorylation of multiple phosphotyrosyl-containing peptides by the phosphatases shp-1 and ptp1b, we applied a chromatographic technique for the analysis of the dephosphorylation products.

SIGNOR-154199

P61586

Q92502

0

gtpase-activating protein

down-regulates activity

0.557

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-260519

Q9UJD0

P20336

1

relocalization

up-regulates activity

0.282

N-terminal interactions of RIMs with RAB3 and MUNC13 regulate DCV fusion. Through N-terminal interactions, RIMs position MUNC13 and recruit DCVs via RAB3, which is located on the vesicle

SIGNOR-264379

P14618

P40763

1

phosphorylation

up-regulates activity

0.443

PKM2 activates transcription of MEK5 by phosphorylating stat3 at Y705. In vitro phosphorylation assays show that PKM2 is a protein kinase using PEP as a phosphate donor

SIGNOR-267716

P04114

O60216

0

transcriptional regulation

down-regulates quantity

0.2

The promoter region of APOB bound RAD21 but not RAD21 p.622 Ala>Thr; expression of wild-type RAD21 in HEK293 cells repressed expression of APOB, compared with control vector.

SIGNOR-259974

P16949

Q9UQM7

0

phosphorylation

down-regulates

0.403

Involved in the regulation of the microtubule (mt) filament system by destabilizing microtubules. Prevents assembly and promotes disassembly of microtubules. In vitro, ser16 of recombinant human stathmin was phosphorylated also by purified cam kinase ii, and in vivo, cam kinase ii activity was indeed stimulated in cd2-triggered jurkat cells. Altogether, our results favor an association of cam kinase ii activity with costimulatory signals of t lymphocyte activation and phosphorylation of stathmin on ser16.

SIGNOR-149640

Q13887

Q14258

0

polyubiquitination

down-regulates quantity by destabilization

0.482

The oestrogen-inducible E3 ligase EFP (oestrogen-responsive finger protein) was identified as a key player in oestrogen-mediated degradation of KLF5, as knockdown and overexpression of EFP increased and decreased KLF5 protein levels respectively, and the decrease continued even when protein synthesis was blocked.

SIGNOR-271908

O15111

Q9Y243

0

phosphorylation

up-regulates

0.414

Although there are likely to be multiple levels of crosstalk between the pi3k-akt and nf-kb pathways, one mechanism has been attributed to direct phosphorylation of the amino acid residue t23 on ikb kinase alfa (ikkalfa) by akt, thereby leading to activation of this kinase upstream of nf-kb akt mediates ikkalpha phosphorylation at threonine 23 akt transiently associates in vivo with ikk and induces ikk activation. Akt mediates ikkalfa phosphorylation at threonine 23.Akt phosphorylates ikkalpha on t23, and this phosphorylation event is a prerequisite for the phosphorylation of p65 at s534 by ikkalpha and beta

SIGNOR-187062

Q16539

O60381

1

phosphorylation

up-regulates

0.43

A mutation of the p38 map kinase phosphorylation site at aa 401 [(s-a)401hbp1] also triggered hbp1 protein instability. While protein stability was compromised by mutation, the specific activities of (s-a)401hbp1 and of wild-type hbp1 appeared comparable for transcriptional repression.

SIGNOR-119138

Q13043

P42574

0

cleavage

up-regulates activity

0.617

In response to apoptotic stimuli, caspase cleavage of mst1 occurs at asp-326 and asp-349, resulting in the separation of its n-terminal kinase domain from the nes-containing c-terminal domain. Thus, caspase cleavage of mst1 serves two purposes: one is activation of mst1 kinase activity and the other is translocation of mst1 into the nucleus.

SIGNOR-109878

P54252

P68400

0

phosphorylation

up-regulates activity

0.2

Here we show that protein casein kinase 2 (CK2)-dependent phosphorylation controls the nuclear localization, aggregation and stability of ataxin-3 (ATXN3), the disease protein in spinocerebellar ataxia type 3 (SCA3). The main phosphorylation of ATXN3 in vivo thus occurred at serine residues within the three conserved UIMs.

SIGNOR-276224

P49674

Q13541

1

phosphorylation

down-regulates

0.2

Mechanistic investigations showed that ck1_ interacted with and phosphorylated 4e-bp1 at two novel sites t41 and t50, which were essential for 4e-bp1 inactivation along with increased mrna translation and cell proliferation.

SIGNOR-203240

O75449

Q92630

0

phosphorylation

down-regulates quantity by destabilization

0.509

DYRK2 mediated phosphorylation is required for Katanin p60 degradation. Serine 42, serine 109 and threonine 133 are likely to be the major DYRK2 phosphorylation sites as single mutations for these sites showed reduced phosphorylation by DYRK2 and the triple mutant showed almost no DYRK2 mediated phosphorylation (Fig. 5d).

SIGNOR-262847

P50750

P49459

1

phosphorylation

up-regulates activity

0.449

CDK9 phosphorylates RNA polymerase II CTD at serine 2 to recruit the RNF20/40 E3 ubiquitin ligase, which is required for H2Bub1, and phosphorylates UBE2A at serine 120 to increase its activity in regulating H2Bub1.

SIGNOR-279025

P84243

P29375

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-264301

P42574

Q13464

1

cleavage

up-regulates

0.734

Rock i is cleaved by casp3 at a conserved detd1113/g sequence and its carboxy-terminal inhibitory domain is removed, resulting in deregulated and constitutive kinase activity.

SIGNOR-106546

P50613

Q01860

1

phosphorylation

up-regulates quantity by stabilization

0.2

Here, we combined molecular and cellular biology with CRISPR/Cas9-mediated genome engineering to pinpoint the function of serine 12 of OCT4 in ESCs. Using chemical inhibitors and an antibody specific to OCT4 phosphorylated on S12, we identified cyclin-dependent kinase (CDK) 7 as upstream kinase. |Phosphorylation of OCT4 on S12 has been previously implicated to stabilize OCT4 by binding to PIN1, thereby preventing ubiquitinylation by WWP2.

SIGNOR-264404

Q00535

O60331

1

phosphorylation

down-regulates

0.364

The interaction of talin with phosphatidylinositol(4) phosphate 5 kinase type i gamma (pipki gamma) regulates pi(4,5)p2 synthesis at synapses and at focal adhesions. Here, we show that phosphorylation of serine 650 (s650) within the talin-binding sequence of human pipki gamma blocks this interaction. At synapses, s650 is phosphorylated by p35/cdk5 and mitogen-activated protein kinase at rest, and dephosphorylated by calcineurin upon stimulation.

SIGNOR-134455

O15294

P49841

0

phosphorylation

up-regulates activity

0.518

But OGT activity is modulated by GSK3beta (XREF_FIG) and GSK3beta activity is known to oscillate through Ser9 phoshorylation.|Here, we found that OGT is phosphorylated at serines 3 or 4 by GSK3beta and that O GlcNAcylation of OGT also occurs on the same or neighboring serine residues, suggesting interacting phosphorylation and O GlcNAcylation events on OGT itself.

SIGNOR-279528

P63000

Q7Z6I6

0

gtpase-activating protein

down-regulates activity

0.403

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-260486

P12931

P19367

1

phosphorylation

down-regulates activity

0.492

Mechanistically, c-Src phosphorylation of HK1 at Tyr732 robustly decreases its K m and increases its V max by disrupting its dimer formation.|Mechanistically, c-Src-mediated Y732 phosphorylation disrupts HK1 dimer formation, alters its enzyme kinetics and eventually enhances enzymatic activity ( ).

SIGNOR-278209

O14757

Q7Z2Z1

1

phosphorylation

down-regulates activity

0.432

In principle, phosphorylation of Treslin by Chk1 may alter its conformation or directly affect its interactions with other proteins to preclude helicase activation.|The fact that the TRCT domain blocks the binding of Chk1 to Treslin suggests that Chk1 suppresses the initiating function of Treslin.

SIGNOR-278924

P08575

P68400

0

phosphorylation

up-regulates

0.442

Mutational analysis of ck2 consensus sites showed that the target for ck2 was in an acidic insert of 19 amino acids in the d2 domain, and ser to ala mutations at amino acids 965, 968, 969, and 973 abrogated ck2 phosphorylation of cd45. Ck2 phosphorylation increased cd45 activity 3-fold toward phosphorylated myelin basic protein,

SIGNOR-65277

Q02363

Q9Y463

0

phosphorylation

down-regulates activity

0.2

Phosphorylation of Thr27 of ID2 by DYRK1 blocks ID2-VHL interaction and preserves HIF2Œ± ubiquitylation.|We report that DYRK1A and DYRK1B kinases phosphorylate ID2 on Threonine-27 (T27).

SIGNOR-279033

P17612

Q9UQL6

1

phosphorylation

up-regulates activity

0.2

PKA/Cdk5-mediated phosphorylation of HDAC5 at Ser279 within the NLS promotes nuclear localization of HDAC5 and interaction with the nuclear corepressor complex

SIGNOR-198658

Q8IXJ6

P15172

1

deacetylation

down-regulates

0.376

Sir2-mediated deacetylation of myod can be expected to inhibit its transcriptional capabilities.

SIGNOR-104251

P16949

O14965

0

phosphorylation

down-regulates activity

0.388

Inhibition of AURKA activity activates stathmin function via reduced phosphorylation and facilitates microtubule destabilization in RB1 -/- cells, heavily impacting the bipolar spindle formation and inducing mitotic cell death selectively in RB1 -/- cells.|Two serine phosphorylation sites, Ser16 and Ser63, in stathmin contain a consensus sequence for AURKA phosphorylation and the mutations in these two serine sites abolished stathmin phosphorylation by AURKA, suggesting that stathmin is a substrate of AURKA for phosphorylation xref , xref .

SIGNOR-278913

P19634

Q16539

0

phosphorylation

up-regulates

0.571

Trophic factor withdrawal: p38 mitogen-activated protein kinase activates nhe1, which induces intracellular alkalinization. activated p38 mapk directly phosphorylated the c terminus of nhe1 within a 40-amino-acid region. Analysis by mass spectroscopy identified four phosphorylation sites on nhe1, thr 717, ser 722, ser 725, and ser 728.

SIGNOR-111043

P10415

Q16539

0

phosphorylation

down-regulates activity

0.334

Bcl-2 phosphorylation by p38 mapkin this study, we identify, by using mass spectrometry techniques and specific anti-phosphopeptide antibodies, ser(87) and thr(56) as the bcl-2 residues phosphorylated by p38 mapk and show that phosphorylation of these residues is always associated with a decrease in the antiapoptotic potential of bcl-2 protein.

SIGNOR-146786

Q00987

Q92831

1

ubiquitination

down-regulates quantity by destabilization

0.621

Consistently, overexpression of MDM2 in p53 null cells caused the reduction of the protein level of PCAF, but not the mRNA level.|MDM2 ubiquitinated PCAF in vitro and in cells.

SIGNOR-278825

Q15796

Q13233

0

phosphorylation

up-regulates activity

0.474

As yet, the apparent discrepancy between these and above data is not clear, but obviously the type of cell under study and the cellular context may play an important role.In endothelial cells, Smad2 activity is stimulated by MEKK1, a component of the Stress Activated Protein Kinase and c-Jun N terminal kinase (SAPK and JNK) pathway.|Phosphorylation of Smad2 by MEKK1 increased its association with Smad4, its nuclear accumulation and its transcription induction activity .

SIGNOR-279064

Q14940

P49407

0

relocalization

down-regulates activity

0.401

Internalization of the Na(+)/H(+) exchanger NHE5 into recycling endosomes is enhanced by the endocytic adaptor proteins beta-arrestin1 and -2, best known for their preferential recognition of ligand-activated G protein-coupled receptors (GPCRs)

SIGNOR-275505

P10636

Q9BXM7

0

phosphorylation

down-regulates activity

0.384

Simultaneously overexpressing PINK1 significantly reduced the levels of exogenous total and phosphorylated tau proteins (Figures 4A,B,E).|Taken together, our data revealed that PINK1 overexpression promoted degradation of abnormal accumulated tau via the autophagy-lysosome pathway, indicating that PINK1 may be a potential target for AD treatment.

SIGNOR-279250

Q86Y07

Q13469

1

phosphorylation

up-regulates

0.369

We demonstrate that vrk2 directly interacts and phosphorylates nfat1 in ser-32 within its n-terminal transactivation domain.

SIGNOR-199263

P30281

P62136

0

dephosphorylation

up-regulates

0.246

These results support the hypothesis that pp1 constitutively keeps cyclin d3 in a stable, dephosphorylated state

SIGNOR-142884

P27361

P01106

1

phosphorylation

up-regulates activity

0.707

ERK1 phosphorylates MYC Ser62 resulting in MYC stabilization and activation

SIGNOR-236250

P11532

Q12955

0

relocalization

up-regulates quantity

0.367

We present evidence for an ankyrin-based mechanism for sarcolemmal localization of dystrophin and beta-DG. Ankyrin-B thus is an adaptor required for sarcolemmal localization of dystrophin, as well as dynactin-4.

SIGNOR-266715

P14923

Q9UI47

0

relocalization

up-regulates quantity

0.484

Overexpression of CTNNA3 in a CTNNA1 negative colon carcinoma cell line resulted in the reassembly of the adherens and tight junctions through the recruitment of CTNNA3 interacting partners such as E-cadherin, β-catenin, plakoglobin, and ZO-14

SIGNOR-265494

O00206

P12931

0

phosphorylation

up-regulates activity

0.588

Src dependent phosphorylation of TLR4 is significantly increased in Cftr-KO cholangiocytes.|TLR4 can be activated through the phosphorylation of its TIR domains by Src, a non receptor tyrosine kinase 28.

SIGNOR-279658

Q15139

P27986

1

phosphorylation

up-regulates activity

0.2

PKD1 phosphorylates p85α to enhance its interaction with PTEN, leading to polarized PTEN activity, thereby regulating neutrophil migration.

SIGNOR-276426

P78527

P42575

1

phosphorylation

up-regulates

0.297

Here we show that dna damage induced by gamma-radiation triggers the phosphorylation of nuclear caspase-2 at the s122 site within its prodomain, leading to its cleavage and activation. This phosphorylation is carried out by the nuclear serine/threonine protein kinase dna-pkcs

SIGNOR-183895

Q15131

P15036

1

phosphorylation

down-regulates quantity by destabilization

0.528

Altogether, these results suggest that CDK10/cyclin M directly controls ETS2 degradation through the phosphorylation of these two serines.

SIGNOR-260914

Q13464

Q14457

1

phosphorylation

up-regulates activity

0.415

Beclin1 is phosphorylated by ROCK1 at T119.

SIGNOR-278198

Q99558

O14920

1

phosphorylation

up-regulates

0.714

Activation of the transcription factor nf-kappab by inflammatory cytokines involves the successive action of nf-kappab-inducing kinase (nik) and two ikappab kinases, ikk-alpha and ikk-beta. Here we show that nik preferentially phosphorylates ikk-alpha over ikk-beta

SIGNOR-55949

P27361

Q9BZI1

1

phosphorylation

up-regulates activity

0.2

To identify the phosphorylated residue, we introduced a serine-to-alanine substitution at residues 294 and 326 and a threonine-to-alanine substitution at residue 331 in Irx2(291–356). Erk1 phosphorylated S294A and T331A, but not S326A (Fig. 4b), indicating that Ser326 is the bona fide MAP kinase target.

SIGNOR-263061

Q68D86

P51955

0

phosphorylation

down-regulates activity

0.2

CCDC102B is recruited to the centrosome by C-Nap1 (also known as CEP250) and interacts with the centrosome linker components rootletin and LRRC45. CCDC102B decorates and facilitates the formation of rootletin filaments. Furthermore, CCDC102B is phosphorylated by Nek2A (an isoform encoded by NEK2) and is disassociated from the centrosome at the onset of mitosis.

SIGNOR-275626

P49841

P20929

1

phosphorylation

down-regulates

0.306

Gsk3b is able to phosphorylate nebulin at two ser sites in the c-terminal region of nebulin localized to the z-disk, thus preventing the interaction of nebulin with neuronal wiscott-aldrich syndrome protein (nwasp), a ubiquitously expressed member of the wasp family, which is involved in actin assembly.

SIGNOR-175659

P17677

Q6UB99

0

transcriptional regulation

up-regulates quantity by expression

0.2

Neurite growth-related genes such as Trkb, Bdnf, Gap43, Coronin 1B, and Rab13 are downregulated in ANKRD11-deficient neurons.

SIGNOR-266736

P98170

O43353

1

ubiquitination

up-regulates activity

0.628

XIAP is the essential E3 for RIPK2 ubiquitination and interacts with RIPK2 through its baculoviral IAP-repeat (BIR).

SIGNOR-280449

Q8IYT8

P06733

1

phosphorylation

down-regulates activity

0.2

Here, we demonstrate that, during deprivation of amino acid and growth factors, ULK1/2 directly phosphorylate key glycolytic enzymes including hexokinase (HK), phosphofructokinase 1 (PFK1), enolase 1 (ENO1), and the gluconeogenic enzyme fructose-1,6-bisphosphatase (FBP1).Phosphorylation of these enzymes leads to enhanced HK activity to sustain glucose uptake but reduced activity of FBP1 to block the gluconeogenic route and reduced activity of PFK1 and ENO1 to moderate drop of glucose-6-phosphate and to repartition more carbon flux to pentose phosphate pathway (PPP), maintaining cellular energy and redox homeostasis at cellular and organismal levels.Similar results were also obtained using ULK2 as the kinase (data not shown).

SIGNOR-274037

Q13153

P03372

1

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

O15503

Q9UKV5

0

ubiquitination

down-regulates quantity by destabilization

0.525

The ubiquitination of Insig-1 is mediated by gp78 and regulated by sterols.|gp78 mediates the degradation of Insig-1 and Insig-2.

SIGNOR-278567

Q96FF9

P53350

0

phosphorylation

down-regulates activity

0.705

Here we show that the mitotic kinases Aurora B and Cyclin-dependent kinase 1 (Cdk1) destabilize interactions between Sororin and the cohesin subunit precocious dissociation of sisters protein 5 (Pds5) by phosphorylating Sororin, leading to release of acetylated cohesin from chromosome arms and loss of cohesion.

SIGNOR-276122

P12931

Q16832

1

phosphorylation

up-regulates

0.38

Here, using baculoviral co-expression of the ddr2 cytosolic domain and src, we show that src targets three tyrosine residues (tyr-736, tyr-740, and tyr-741) in the activation loop of ddr2 for phosphorylation. This phosphorylation by src stimulates ddr2 cis-autophosphorylation of additional tyrosine residues.

SIGNOR-140767

P46934

Q9NV92

0

relocalization

down-regulates activity

0.568

Ndfip1 is primarily localized in the Golgi apparatus where it recruits Nedd4-2 to mediate the degradation of mature hERG proteins during channel trafficking to the plasma membrane. Although Ndfip2 directs Nedd4-2 to the Golgi apparatus, it also recruits Nedd4-2 to the multivesicular bodies (MVBs), which may impair MVB function and impede the degradation of mature hERG proteins mediated by Nedd4-2.

SIGNOR-260995

O95613

Q76N32

0

relocalization

up-regulates activity

0.34

We also found that Cep68 forms a complex with Cep215 (also known as Cdk5Rap2) and PCNT (also known as pericentrin), two PCM (pericentriolar material) proteins involved in centriole engagement. |Cep68 stabilization increases the amount of PCNT at metaphase centrosomes, but does not affect its removal at the end of mitosis

SIGNOR-275623

P21399

P17252

0

phosphorylation

down-regulates

0.2

Irp1 ser-711 is a phosphorylation site, critical for regulation of rna-binding and aconitase activities.

SIGNOR-133188

Q99612

P18847

1

transcriptional regulation

up-regulates quantity by expression

0.394

KLF6 binds directly to and activates the ATF3 promoter.

SIGNOR-266051

P06493

Q9UNH5

1

phosphorylation

up-regulates activity

0.54

We found that Cdc14A is phosphorylated on Ser411, Ser453 and Ser549 by Cdk1 early in mitosis and becomes dephosphorylated during late mitotic stages.

SIGNOR-278264

Q96GD4

Q69YH5

1

phosphorylation

down-regulates activity

0.446

This result demonstrates that the three sites of Repo-Man (Ser-543, Ser-977, and Ser-981) are phosphorylated by Aurora B in early mitosis. We uncover that PP1γ is recruited to mitotic chromosomes by its regulatory subunit Repo-Man in the absence of Aurora B activity and that Aurora B regulates dissociation of PP1γ by phosphorylating and disrupting PP1γ-Repo-Man interactions on chromatin.

SIGNOR-274001

P68871

P19338

0

post transcriptional regulation

up-regulates quantity by expression

0.2

Nucleolin binds human β-globin mRNA. A Nucleolin-Binding 3′ Untranslated Region Element Stabilizes β-Globin mRNA In Vivo

SIGNOR-251844

Q9Y463

Q9UKV0

1

phosphorylation

down-regulates

0.2

Mirk activated mef2 not through direct phosphorylation of mef2 but by phosphorylation of its inhibitors, the class ii histone deacetylases (hdacs). Mef2 is sequestered by class ii hdacs such as hdac5 and mef2-interacting transcriptional repressor (mitr). Mirk antagonized the inhibition of mef2c by mitr, whereas kinase-inactive mirk was ineffective. Mirk phosphorylates class ii hdacs at a conserved site within the nuclear localization region, reducing their nuclear accumulation in a dose-dependent and kinase-dependent manner

SIGNOR-235813

P63000

Q96HP0

0

guanine nucleotide exchange factor

up-regulates activity

0.528

Dock6 is a guanine nucleotide exchange factor (GEF) that activates the Rho family guanosine triphosphatases Rac1 and Cdc42 to regulate the actin cytoskeleton.

SIGNOR-275670

Q02078

Q9UKX2

1

transcriptional regulation

up-regulates quantity by expression

0.325

Myocyte enhancer factor-2 and serum response factor binding elements regulate fast Myosin heavy chain transcription in vivo. We show that the upstream promoter region of the gene most abundantly expressed in mouse skeletal muscles, IIb MyHC, retains binding activity and transcriptional activation for three positive transcription factors, the serum response factor, Oct-1, and myocyte enhancer factor-2, whereas the other two genes (IIa and IId/x) have nucleotide substitutions in these sites that reduce binding and transcriptional activation

SIGNOR-238703

Q92830

P0DPK5

1

acetylation

down-regulates activity

0.2

The HAT module within the SAGA and ADA complexes acetylates histone H3, mainly on residues K9 and K14.

SIGNOR-269598

O00750

P00533

0

phosphorylation

up-regulates

0.44

The n-terminal region of pi3k-c2beta was found to selectively interact with the egf receptor in vitro, suggesting that it mediates the association of this pi3k with the receptor.

SIGNOR-77195

Q14938

Q02535

1

transcriptional regulation

down-regulates quantity

0.2

By integrating transcriptomic profiling (RNA-seq) of Nfia- and Nfix-deficient GNPs with epigenomic profiling (ChIP-seq against NFIA, NFIB and NFIX, and DNase I hypersensitivity assays), we reveal that these transcription factors share a large set of potential transcriptional targets, suggestive of complementary roles for these NFI family members in promoting neural development

SIGNOR-268885

Q14721

P18433

0

dephosphorylation

down-regulates

0.2

Ptpalpha inhibits kv channels more strongly than ptpepsilon;this correlates with constitutive association of ptpalpha with kv2.1, driven by membranal localization of ptpalpha.

SIGNOR-148301

P24941

O43303

1

phosphorylation

down-regulates activity

0.515

GST-tagged recombinant CP110 (GST-wt) was robustly phosphorylated by cyclin E/CDK2 (Figure 2A). Expression of a mutant derivative of CP110 refractory to CDK phosphorylation provokes marked polyploidy. We localized the majority (nine of ten) of potential CDK2 phosphorylation sites in CP110 to an amino-terminal fragment (GST-ΔN1; Figure 1B)

SIGNOR-265956

P06241

P12318

1

phosphorylation

up-regulates activity

0.534

To identify the FcgammaRII-phosphorylating protein tyrosine kinase (PTK), we used the combination of an in vitro and an in vivo approach. In an in vitro assay using recombinant cytoplasmic tails of the different FcgammaRII isoforms as well as tyrosine exchange mutants, we show that each of the BCR-associated PTKs (Lyn, Blk, Fyn, and Syk) shows different phosphorylation patterns with regard to the different FcgammaR isoforms and point|Fyn and Blk definitely phosphorylate Y-282 in the ITAM of Fc_RIIa/c, whereas the non-ITAM tyrosine residue (Y-275) becomes phosphorylated by Syk, as the phosphorylation of double point mutants shows. In addi-tion to these tyrosine residues, Fyn, Blk, and Syk might phosphorylate the most C-terminal tyrosine residue (Y-298) because altering this tyrosine residue together with one of the tyrosine residues clearly shown to be phosphorylated by the respective PTK results in the abrogation of phosphorylation.

SIGNOR-249336

P49841

Q9UBN7

1

phosphorylation

up-regulates activity

0.381

GSK3beta was found to co-localize with HDAC6 in hippocampal neurons, and inhibition of GSK3beta resulted in decreased binding of antibody to phosphoserine-22, a potential GSK3beta phosphorylation site in HDAC6.|This suggests that GSK3\u03b2 may directly phosphorylate HDAC6 at this site, although further work with purified proteins is needed to determine whether this is the case.|The fact that HDAC6 is the predominant cytoplasmic deacetylase in neurons suggests that GSK3beta dependent phosphorylation may enhance HDAC6 activity, resulting in a decrease in acetylation of tubulin and an inhibition of both mitochondrial motility and the transport of other kinesin-1 dependent cargoes.

SIGNOR-278941

P45983

P15336

1

phosphorylation

up-regulates

0.78

Activating transcription factor-2 (atf2) was found to be a target of the jnk signal transduction pathway. Atf2 was phosphorylated by jnk on two closely spaced threonine residues within the nh2-terminal activation domain.

SIGNOR-33914

P00519

Q8N2M8

1

phosphorylation

up-regulates activity

0.2

In biochemical assays and in Xenopus growth cones we find that Abl kinase activity enhances the association or co-localization of CLASP2 and F-actin, consistent with previous reports of CLASP binding to actin [Tsvetkov et al., ].|In vitro, Abl phosphorylates CLASP with a Km of 1.89 \u00b5M, indicating that CLASP is a bona fide substrate.

SIGNOR-280166

Q15797

Q9P0J1

0

dephosphorylation

down-regulates

0.243

We show that the mammalian pdps are important in dephosphorylation of bmp-activated smad1 but not tgf-beta-activated smad2 or smad3. Thus, pdps specifically inactivate smads in the bmp/dpp pathway. [...] These observations suggest that pdp1 and pdp2 are important for dephosphorylation of smad1.

SIGNOR-144876

P38117

Q8IXQ9

0

methylation

down-regulates activity

0.2

Accordingly, we found that METTL20-mediated methylation of ETFβ in vitro reduced its ability to receive electrons from the medium chain acyl-CoA dehydrogenase and the glutaryl-CoA dehydrogenase. In conclusion, the present study establishes METTL20 as the first human KMT localized to mitochondria and suggests that it may regulate cellular metabolism through modulating the interaction between its substrate ETFβ and dehydrogenases.

SIGNOR-269450