GleghornLab/Signor_2class · Datasets at Hugging Face

IdA string	IdB string	labels int64	mechanism string	effect string	score float64	sentence string	signor_id string
P35968	P17706	0	dephosphorylation	down-regulates activity	0.566	We show that a TCPTP substrate-trapping mutant interacts with VEGFR2. Moreover, TCPTP dephosphorylates VEGFR2 in a phosphosite-specific manner, inhibits its kinase activity and prevents its internalization from the cell surface. \|The autophosphorylation sites Tyr1054/1059 and Tyr1214 were dephosphorylated by TCPTP (Fig. 4B). Tyr996, the functional significance of which is currently uncertain (Olsson et al., 2006), was a TCPTP target as well.	SIGNOR-248399
Q7Z2K8	P51608	0	post transcriptional regulation	up-regulates quantity by expression	0.298	MeCP2 binds to the promoter region of six target genes. ChIP with anti-MeCP2 antibody shows that MeCP2 binds to the promoter regions of activated targets Sst, Oprk1, Gamt, and Gprin1, and repressed targets Mef2c and A2bp1.	SIGNOR-264679
Q9BXM7	O75439	0	cleavage	down-regulates quantity by destabilization	0.339	Using an unbiased RNA-mediated interference (RNAi)-based screen, we identified four mitochondrial proteases, mitochondrial processing peptidase (MPP), presenilin-associated rhomboid-like protease (PARL), m-AAA and ClpXP, involved in PINK1 degradation. We find that PINK1 turnover is particularly sensitive to even modest reductions in MPP levels. Moreover, PINK1 cleavage by MPP is coupled to import such that reducing MPP activity induces PINK1 accumulation at the mitochondrial surface, leading to Parkin recruitment and mitophagy.	SIGNOR-261363
P68400	P11413	1	phosphorylation	up-regulates activity	0.2	CK2 phosphorylates G6PD T145 under ionizing radiation	SIGNOR-277890
Q00535	P10636	1	phosphorylation	down-regulates activity	0.763	We found that cdk5 phosphorylated tau(441) at Thr-181, Ser-199, Ser-202, Thr-205, Thr-212, Ser-214, Thr-217, Thr-231, Ser-235, Ser-396, and Ser-404, but not at Ser-262, Ser-400, Thr-403, Ser-409, Ser-413, or Ser-422. GSK-3beta phosphorylated all the cdk5-catalyzed sites above except Ser-235.	SIGNOR-249321
Q9HBH9	P06730	1	phosphorylation	up-regulates	0.56	Inhibition of mammalian target of rapamycin induces phosphatidylinositol 3-kinase-dependent and mnk-mediated eukaryotic translation initiation factor 4e phosphorylation.Therefore, eif4e is considered a survival protein involved in cell cycle progression, cell transformation, and apoptotic resistance. Phosphorylation of eif4e (usually at ser209) increases its binding affinity for the cap of mrna and may also favor its entry into initiation complexes.	SIGNOR-157537
Q13315	P15927	1	phosphorylation	up-regulates	0.809	Replication protein a (rpa) is a single-stranded dna (ssdna) binding protein involved in various processes, including nucleotide excision repair and dna replication. The 32 kda subunit of rpa (rpa32) is phosphorylated in response to various dna-damaging agents, and two protein kinases, ataxia-telangiectasia mutated (atm) and the dna-dependent protein kinase (dna-pk) have been implicated in dna damage-induced phosphorylation of rpa32we show that both dna-pk and atm phosphorylate rpa32 on thr21 in vitro.	SIGNOR-121861
Q14686	Q4ZG55	1	transcriptional regulation	up-regulates quantity by expression	0.2	Herein, using growth-regulating estrogen receptor binding 1 (GREB1) as an ERα target gene in Ishikawa cells, we demonstrate that nuclear receptor co-activator 6 (NCOA6) is essential for estradiol (E2)/ERα-activated GREB1 transcription. We found that NCOA6 associates with the GREB1 promoter and enhancer in an E2-independent manner and that NCOA6 knockout reduces chromatin looping, enhancer-promoter interactions, and basal GREB1 expression in the absence of E2.	SIGNOR-265883
Q12834	P53350	0	phosphorylation	down-regulates quantity by destabilization	0.977	Plk1 directly bound to Cdc20 and phosphorylates it on serine-170 located in CRY-box. Whereas wild-type Cdc20 was degraded according to progress cell cycle beyond mitosis, the phosphorylation-defective mutant, which serine-170 was changed into alanine, was not destroyed in early G1 phase.	SIGNOR-276493
P04406	Q13043	0	phosphorylation	up-regulates activity	0.279	Interestingly, GAPDH is phosphorylated by Mst1 to a comparable extent as its known substrate MBP, suggesting that GAPDH is a good substrate of Mst1 at least in vitro.\|Moreover, interaction of Mst1 with GAPDH caused a robust phosphorylation of GAPDH and markedly increased the Mst1 activity in cells.	SIGNOR-279295
Q9GZV5	P07947	0	phosphorylation	up-regulates activity	0.317	Yes directly phosphorylates YAP and TAZ, resulting in their increased nuclear localization and transcriptional activity.Analysis by mass spectrometry identified Tyr391 and Tyr407 as the two phosphorylation sites of YAP, whereas Tyr305 was the sole phosphorylated residue of TAZ (Fig. 5F and fig. S4, A to C).	SIGNOR-277654
P68400	P54252	1	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
Q16611	P99999	1	relocalization	up-regulates	0.566	Allosteric activation of bak induces its intramembranous oligomerization into a proposed pore for cytochrome c efflux	SIGNOR-105206
P18031	P08581	1	dephosphorylation	down-regulates activity	0.637	It has been reported that the protein tyrosine phosphatase PTP1B could inactivate MET by direct dephosphorylation of Tyr 1234 and 1235 in its activation loop, and that this dephosphorylation takes place in peri-nuclear region of the cell [ xref ].	SIGNOR-277001
Q9Y4P1	P31749	0	phosphorylation	up-regulates activity	0.31	In this study, we identified a novel phosphorylation site at Ser34 of ATG4B induced by AKT in HCC cells.\| In brief, our results demonstrate for the first time that the phosphorylation of ATG4B at Ser34 participates in the metabolic reprogramming of HCC cells via repressing mitochondrial function, which possibly results from the Ser34 phosphorylation-induced mitochondrial enrichment of ATG4B and the subsequent inhibition of F1Fo-ATP synthase activity.	SIGNOR-275834
P11388	P49841	0	phosphorylation	down-regulates quantity by destabilization	0.348	This study also reports the novel finding that topoIIα may be a target of GSK3β phosphorylation. Evidence suggests that CK2 serves as a priming kinase, through phosphorylation at Ser1365, for GSK3β-mediated phosphorylation at Ser1361.	SIGNOR-276301
Q5XPI4	P83916	1	polyubiquitination	down-regulates quantity by destabilization	0.2	In the present study, we report that HP1α and β undergo proteasomal degradation in lamin A/C knock-down cells and show by ectopic expression, RNAi and binding studies that the RING finger ubiquitin ligase RNF123 is directly involved in HP1 degradation.	SIGNOR-272034
O75475	O00311	0	phosphorylation	up-regulates	0.334	We now report identification of the cdc7-activator of s-phase kinase (ask) heterodimer as a novel interactor of ledgf. the kinase phosphorylated ledgf in vitro, with ser-206 being the major target, and ledgf phosphorylated at this residue could be detected during s phase of the cell cycle. Ledgf potently stimulated the enzymatic activity of cdc7-ask, increasing phosphorylation of mcm2 in vitro by more than 10-fold.	SIGNOR-25763
P01112	Q06124	0	dephosphorylation	up-regulates activity	0.681	Here we identify SHP2 as the ubiquitously expressed tyrosine phosphatase that preferentially binds to and dephosphorylates Ras to increase its association with Raf and activate downstream proliferative Ras/ERK/MAPK signalling.	SIGNOR-252094
Q9BZY9	Q96P20	1	ubiquitination	down-regulates quantity by destabilization	0.489	Taken together, these data indicated that TRIM31 directly induced the K48-linked ubiquitination of NLRP3 through its E3 ligase activity.\|Taken together, these results indicated that TRIM31 could promote proteasomal degradation of NLRP3.	SIGNOR-278603
P35222	Q9Y297	0	ubiquitination	down-regulates	0.872	Here we show that fwd1 (the mouse homologue of slimb/betatrcp), an f-box/wd40-repeat protein, specifically formed a multi-molecular complex with beta-catenin, axin, gsk-3beta and apc. Mutations at the signal-induced phosphorylation site of beta-catenin inhibited its association with fwd1. Fwd1 facilitated ubiquitination and promoted degradation of beta-catenin, resulting in reduced cytoplasmic beta-catenin levels.	SIGNOR-67374
P07948	Q9NWQ8	1	phosphorylation	up-regulates activity	0.725	Here we show that Lyn interacts with C-terminal Src kinase-binding protein (Cbp), an adaptor protein that recruits negative regulators C-terminal Src kinase (Csk)/Csk-like protein-tyrosine kinase (Ctk). Lyn phosphorylated Cbp on several tyrosine residues, including Tyr314, which recruited Csk/Ctk to suppress Lyn kinase activity.Thus, a single phosphotyrosine residue on Cbp coordinates a two-phase process involving distinct negative regulatory pathways to inactivate, then degrade, Lyn.	SIGNOR-262898
P49841	Q9NX09	1	phosphorylation	down-regulates quantity by destabilization	0.339	It has been reported that GSK3beta phosphorylates REDD1 at residues Thr23 and Thr25, resulting in REDD1 recruitment to the Cullin 4a-beta-Trcp E3 ligase complex.	SIGNOR-279526
P11362	P0C6X7-PRO_0000037310	1	chemical inhibition	down-regulates activity	0.2	Pyrimidine 13 showed good potency against all the human VEGFR receptors with an IC50 of 10, 30, and 47 nM for VEGFR-1, -2, and -3, respectively. Significant activity was also seen against the closely related tyrosine receptor kinases PDGFRβ, c-Kit, FGF-R1, and c-fms with IC50’s of 84, 74, 140, and 146 nM, respectively.	SIGNOR-260150
Q99576	Q12778	1	relocalization	down-regulates activity	0.301	GILZ inhibits FOXO1, FOXO3, and FOXO4 transcriptional activities measured with natural or synthetic FOXO-responsive promoters in HL-60 cells.	SIGNOR-256146
P33316-2	P06493	0	phosphorylation	up-regulates quantity	0.386	DUTPase Is Phosphorylated at a Consensus Cyclin-dependent Protein Kinase Site: in Vitro Phosphorylation of Ser-11 by p34cdc2. It is conceivable that the exclusive phosphorylation of DUT-N may play a role in nuclear targeting of this protein. Taken a step further, Ser-11 may confer the ability of DUT-N to localize in specific regions of the nucleus where the dUTPase function is required. The Ser-11 Ala mutant should aid in the testing of these hypotheses.	SIGNOR-262693
P03372	P26045	0	dephosphorylation	up-regulates activity	0.2	Our recent studies further demonstrated that PTPH1 dephosphorylates estrogen receptor at Y537, increases estrogen receptor stability and nuclear accumulation, and enhances breast cancer sensitivity to anti-estrogens [ ].	SIGNOR-277127
P67775	P84022	1	dephosphorylation	down-regulates	0.2	Accordingly, smad3-associated pp2a activity was found under hypoxic conditions. Hypoxia attenuated the nuclear accumulation of tgf-beta-induced smad3 but did not affect smad2. Moreover, the influence of tgf-beta on a set of smad3-activated genes was attenuated by hypoxia, and this was reversed by chemical pp2a inhibition. Our data demonstrate the existence of a smad3-specific phosphatase and identify a novel role for pp2a.	SIGNOR-167480
Q99741	P53350	0	phosphorylation	up-regulates	0.566	Binding between cdc6 and plk1 occurs through the polo-box domain of plk1, and cdc6 is phosphorylated by plk1 on t37. These results suggest that plk1-mediated phosphorylation of cdc6 promotes the interaction of cdc6 and cdk1, leading to the attenuation of cdk1 activity, release of separase, and subsequent anaphase progression.	SIGNOR-169184
P01111	Q9Y397	0	palmitoylation	up-regulates activity	0.404	Covalent lipid modifications mediate the membrane attachment and biological activity of Ras proteins. All Ras isoforms are farnesylated and carboxyl-methylated at the terminal cysteine; H-Ras and N-Ras are further modified by palmitoylation. Here we report that H- and N-Ras are palmitoylated by a human protein palmitoyltransferase encoded by the ZDHHC9 and GCP16 genes. DHHC9 is an integral membrane protein that contains a DHHC cysteine-rich domain. GCP16 encodes a Golgi-localized membrane protein.	SIGNOR-261355
O94989	P60953	1	guanine nucleotide exchange factor	up-regulates activity	0.556	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-260541
P11309	Q92597	1	phosphorylation	down-regulates activity	0.2	Collectively, we find that PIM1 expression leads to increased levels of NDRG1 pS330, and PIM1 dependent NDRG1 phosphorylation decreases NDRG1 protein stability.\|NDRG1 is phosphorylated by PIM1 at serine 330 (pS330), and the level of NDRG1 pS330 is associated higher grade prostate tumors.	SIGNOR-279308
P84022	Q9NYA4	0	dephosphorylation	down-regulates	0.517	Here we demonstrate that myotubularin-related protein 4	SIGNOR-163034
Q9NR80	P12931	0	phosphorylation	up-regulates	0.312	This observation strongly argues for the positive role of tyr94 phosphorylation in egf-induced asef activation following the activation of rac1.	SIGNOR-179601
Q9NQS7	P06493	0	phosphorylation	up-regulates	0.759	Here, we report that cdk1 phosphorylates thr 59 and thr 388 on inner centromere protein (incenp), which regulates the localization and kinase activity of aurora-b from prophase to metaphase. The replacement of endogenous incenp with t388a resulted in the delay of progression from metaphase to anaphase.	SIGNOR-143387
P06400	P06493	0	phosphorylation	down-regulates	0.688	The retinoblastoma gene product (prb) is a nuclear phosphoprotein that is thought to play a key role in the negative regulation of cellular proliferation. The active form of prb is underphosphorylated. Using synthetic peptides corresponding to potential cdc2 phosphorylation sites, we have developed a strategy which has allowed the identification of five sites. S249, t252, t373, s807 and s811 are phosphorylated in vivo, and in each case these sites correspond closely to the consensus sequence for phosphorylation by p34cdc2.	SIGNOR-21564
P27707	Q13315	0	phosphorylation	up-regulates activity	0.399	Here we report that ATM phosphorylation of dCK on Serine 74 is essential to activate the G2/M checkpoint in response to DNA damage.\|Together, these results indicate that the dCK-Cdk1 interaction is enhanced in response to DNA damage and that ATM mediated dCK Serine 74 phosphorylation is required for the interaction.	SIGNOR-278221
P07948	Q96P20	1	phosphorylation	down-regulates	0.29	Lyn phosphorylates NLRP3 at Tyr 918 and controls NLRP3 ubiquitination.\|Therefore, our data collectively indicate that Lyn inhibits the NLRP3 inflammasome in vivo.	SIGNOR-278485
P17252	Q13976	1	phosphorylation	up-regulates	0.344	Antibodies generated against phosphorylated threonine 58 were used to demonstrate phosphorylation in response to pma treatment of the cells with kinetics similar to vasodilator-stimulated phosphoprotein phosphorylation. A phospho-mimetic mutation at this site (t58e) generated a partially activated pkg that was more sensitive to cgmp levels. A phospho- mutation (t58a) revealed that this residue is important but not sufficient for pkg activation by pkc.	SIGNOR-98803
Q16539	P22415	1	phosphorylation	up-regulates activity	0.552	Following uv irradiation, usf-1 is phosphorylated by the p38 stress-activated kinase on threonine 153 and directly up-regulates expression of the pomc, mc1r, tyr, tyrp-1 and dct genes	SIGNOR-185572
Q16512	O15530	0	phosphorylation	up-regulates	0.567	It is shown that activation in vitro and in vivo involves the activation loop phosphorylation of prk1/2 by 3-phosphoinositide-dependent protein kinase-1 (pdk1) /pdk1 phosphorylates the prks at their conserved activation loop threonines (thr-774 and thr-816 for prk1 and prk2, respectively)	SIGNOR-76640
Q8IVA1	P35398	0	transcriptional regulation	up-regulates quantity by expression	0.2	RORα regulates the expression of several genes in Purkinje cells. RORα becomes highly expressed in postmitotic Purkinje cells. It regulates their maturation, particularly dendritic differentiation. Dendritogenesis and the expression of several genes, including Shh, Itpr1, Pcp4, Calb1, Pcp2, and Slc1a6, normally expressed in mature Purkinje cells, are inhibited in RORα-deficient mice.	SIGNOR-266849
Q9NX95	P33176	0	relocalization	up-regulates activity	0.56	Conventional kinesin I heavy chain binds to syntabulin and associates with syntabulin-linked syntaxin vesicles in vivo. These findings suggest that syntabulin functions as a linker molecule that attaches syntaxin-cargo vesicles to kinesin I, enabling the transport of syntaxin-1 to neuronal processes.	SIGNOR-264811
P68400	P51636	1	phosphorylation	up-regulates activity	0.32	We show that caveolin-2 is phosphorylated in vivo at two serine residues and that the phosphorylation of caveolin-2 is necessary for its actions as a positive regulator of caveolin-1 during organelle biogenesis in prostate cancer cells. Mutation of the primary phosphorylation sites on caveolin-2, serine 23 and 36, reduces the number of plasmalemma-attached caveolae	SIGNOR-101110
Q14938	P54756	1	transcriptional regulation	up-regulates quantity	0.2	For example, within the NFI targetome, we identified 6 collagen genes, 13 genes encoding potassium channel or glutamate receptor subunits and a range of factors related to axon guidance (e.g. Slit1, Robo1, Epha4, Epha5, Epha8)	SIGNOR-268909
Q9HAZ1	P00519	1	phosphorylation	down-regulates	0.272	Here, we identify clk1, clk4, mst1, mst2 and ttk (also known as mps1) as novel thr735 kinases in vitro / phosphorylation of thr735 in c-abl is critical for binding to 14-3-3	SIGNOR-181052
P49841	P24723	0	phosphorylation	down-regulates	0.2	Gsk3 is different from most kinases in that it is constitutively partially active and the most common regulatory mechanism is inhibition by phosphorylation of ser21 in gsk3_ or ser9 in gsk3_. This inhibitory phosphorylation can be mediated by several kinases, such as akt/protein kinase b (pkb), protein kinase c (pkc) and protein kinase a (pka).	SIGNOR-188585
P31749	Q92900	1	phosphorylation	up-regulates activity	0.257	AKT-Mediated UPF1 Phosphorylation at T151 Promotes UPF1 Helicase Activity	SIGNOR-277597
P31939	Q9UM73	0	phosphorylation	up-regulates activity	0.377	ATIC and VASP phosphorylation is dependent on NPM-ALK kinase activity. ATIC activity is enhanced in the presence of NPM-ALK in vitro.The ATIC activity is enhanced by NPM-ALK in HEK-293T-Rex cells.	SIGNOR-276171
O14757	Q13164	0	phosphorylation	up-regulates activity	0.276	Moreover, we demonstrate that ERK5 facilitates Chk1 phosphorylation induced by IR.\|Since we have found that ERK5 was able to accelerate the phosphorylation and activation of IR-induced Chk1, therapeutic targeting of Chk1 in NSCLC cells with high ERK5 expression might be an effective strategy for overcoming radioresistance.	SIGNOR-280028
Q9NR96	Q9NWF9	0	ubiquitination	down-regulates quantity by destabilization	0.406	Here we describe how a RING finger protein, Triad3A, acts as an E3 ubiquitin-protein ligase and enhances ubiquitination and proteolytic degradation of some TLRs. Triad3A overexpression promoted substantial degradation of TLR4 and TLR9 with a concomitant decrease in signaling, but did not affect TLR2 expression or signaling.	SIGNOR-271505
P12931	Q15746	1	phosphorylation	up-regulates	0.417	Ec mlck-1 is phosphorylated by p60(src) on tyr(464) and tyr(471), resulting in a 2- to 3-fold increase in ec mlck-1 enzymatic activity.	SIGNOR-85009
O75688	P24941	1	dephosphorylation	down-regulates activity	0.362	CDK2 can be dephosphorylated and inactivated by protein phosphatase type 2C beta isoform long (PP2Cbetal), a unique phosphatase that was originally cloned from human liver.	SIGNOR-277153
A8MYZ6	Q13627	0	phosphorylation	down-regulates	0.305	Additionally, ck1, dyrk1a, and cdk2 also phosphorylate foxos at various sites to inhibit foxos activity	SIGNOR-183680
Q96KG7	P12931	0	phosphorylation	up-regulates activity	0.378	Our data suggest that c-Src augments the phosphorylation of MEGF10 and helps form a signaling complex.\|These results indicate that overexpressed MEGF10 is phosphorylated by c-Src.	SIGNOR-279290
P17612	P16949	1	phosphorylation	down-regulates	0.309	Phosphorylation at either ser(16) or ser(63) strongly reduced or abolished the ability of stathmin to bind to and sequester soluble tubulin and its ability to act as a catastrophe factor by directly binding to the microtubules. The known in vivo phosphorylation sites of stathmin are ser-16 and ser-63 for cyclic amp-dependent protein kinase (pka).	SIGNOR-38318
O75676	P27361	0	phosphorylation	up-regulates	0.586	Rsk-b is a p38alphamapk substrate, and activated by p38alphamapk and, more weakly, by erk1	SIGNOR-60998
Q92830	Q5TEC6	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-269599
Q13555	P07101	1	phosphorylation	up-regulates activity	0.332	In both isoforms, Ser-40 was found to be phosphorylated by PKA, and Ser-19 and Ser-40 were found to be phosphorylated by CaM-PK II. The putative phosphorylation site generated by alternative splicing (Ser-31) was phosphorylated specifically by CaM-PK II in TH-2 only. \| Unlike TH-1, phosphorylation of TH-2 by CaM-PK II resulted in an increase of the Ki value for dopamine.	SIGNOR-250709
Q9Y5Q3	P49841	0	phosphorylation	down-regulates	0.2	We showed that c-maf and mafb, like mafa, are indeed phosphorylated by gsk-3/ we demonstrated that phosphorylation by gsk-3 is conserved among the large maf proteins. It couples ubiquitination/degradation and transcriptional activation and modulates maf biological activity.	SIGNOR-159476
P12931	P54646	1	phosphorylation	down-regulates activity	0.258	We show here that Src signaling leads to direct phosphorylation of the AMPK-α subunit on a novel site, tyrosine 179, resulting in suppression of AMPK-T172 phosphorylation and autophagy upon integrin-mediated cell adhesion.	SIGNOR-277573
Q9NX47	P00441	1	ubiquitination	down-regulates quantity by destabilization	0.2	Mitochondrial ubiquitin ligase MITOL ubiquitinates mutant SOD1 and attenuates mutant SOD1-induced reactive oxygen species generation	SIGNOR-272982
O43524	O43638	0	transcriptional regulation	down-regulates quantity by repression	0.2	Fkhl18 suppressed the transcriptional activity of FoxO3a and FoxO4.	SIGNOR-261610
Q13371	P25098	0	phosphorylation	down-regulates activity	0.2	The phosphorylation of purified phosducin and PhLP by recombinant GRK2 proceeds rapidly and stoichiometrically (0.82 +/- 0.1 and 0.83 +/- 0.09 mol of P (i)/mol of protein, respectively).	SIGNOR-279178
Q14524	Q13554	0	phosphorylation	up-regulates activity	0.408	Among the sites identified, only six were previously suggested to be the targets for specific kinases using in silico and/or in vitro analyses: S36 and S525 were attributed to the regulation by PKA; S484 and S664 were assigned to the serum- and glucocorticoid-inducible kinase 3 (SGK3); and S516 and S571 were ascribed to CaMKII (reviewed in Marionneau and Abriel, 2015). In marked contrast, several previously described phosphorylation sites were not detected in the present study, including the PKA-dependent S528, the CaMKII-associated T594, the PKC-dependent S1506, the adenosine monophosphate–activated protein kinase (AMPK)–dependent T101 (Liu et al., 2019), and the six Fyn-dependent tyrosines (Ahern et al., 2005; Iqbal et al., 2018).\|The simplest interpretation of these findings is that these three phosphorylation clusters, at positions S457-S460, S483-T486, and S664-S671, are likely involved in regulating the basal and/or gating properties of native cardiac NaV1.5 channels. Conversely, the other phosphorylation sites, with lower stoichiometries, may play spatially or temporally distinct roles in the physiological or more pathophysiological regulation of channel expression or gating. \| Remarkably, this MS analysis also revealed that the vast majority of identified phosphorylation sites (at least 26) are clustered, suggesting concomitant phosphorylation and roles in regulating channel expression and/or function. Unexpectedly, however, except for S664, S667, and S671, no apparent effects of phosphomimetic or phosphosilent mutations were observed on heterologously expressed (in HEK-293 cells) NaV1.5	SIGNOR-275773
O14641	P48730	0	phosphorylation	up-regulates	0.534	Ck1_/__dependent phosphorylation of dvl2 at s143 and t224and that this event is critical to interact with plk1 in early stages of the cell cycle	SIGNOR-197547
P30566	Q96KS0	0	hydroxylation	up-regulates activity	0.2	ADSL is hydroxylated by EglN2 on Proline 24. An integrated transcriptomics and metabolomics analysis reveals that ADSL activates the oncogenic cMYC pathway by regulating cMYC protein level via a mechanism requiring ADSL proline 24 hydroxylation. ADSL regulates cMYC protein level through adenosine levels	SIGNOR-266613
Q05209	P52565	1	dephosphorylation	up-regulates activity	0.2	Integrin-bound PTP-PEST dephosphorylates RhoGDI1.\|Translocation of Src phosphorylated RhoGDI1 to the cell 's leading edge promotes local activation of Rac1 and Cdc42, whereas dephosphorylation of RhoGDI1 by integrin bound PTP-PEST promotes RhoGDI1 release from the membrane and sequestration of inactive Rac1 and Cdc42 in the cytoplasm.\|Translocation of Src-phosphorylated RhoGDI1 to the cell's leading edge promotes local activation of Rac1 and Cdc42, whereas dephosphorylation of RhoGDI1 by integrin-bound PTP-PEST promotes RhoGDI1 release from the membrane and sequestration of inactive Rac1/Cdc42 in the cytoplasm.	SIGNOR-277175
P08581	P18031	0	dephosphorylation	down-regulates activity	0.637	It has been reported that the protein tyrosine phosphatase PTP1B could inactivate MET by direct dephosphorylation of Tyr 1234 and 1235 in its activation loop, and that this dephosphorylation takes place in peri-nuclear region of the cell [ xref ].	SIGNOR-277001
P46527	O15355	0	dephosphorylation	up-regulates activity	0.2	By using genomic phosphatase screening, we identified a PPM family phosphatase, PPM1G, which could reduce p27 phosphorylation at T198.\|Functionally, ectopic expression of PPM1G enhanced p27 protein stability and delayed cell cycle progression from G1 to S phase.	SIGNOR-277112
P30291	Q13153	0	phosphorylation	down-regulates	0.299	Kinases targeted sequentially to the neck, cla4/pak and cdc5/polo, are responsible for stepwise phosphorylation and down-regulation of swe1.	SIGNOR-123528
P24863	Q92585	0	relocalization	up-regulates	0.447	Cycc:cdk8 and cyct1:cdk9/p-tefb are recruited with notch and associated coactivators (mam, skip) to the hes1 promoter in signaling cells.	SIGNOR-130709
P06493	P29590	1	phosphorylation	down-regulates	0.345	Here, we show that klhl20, a cullin3 (cul3) substrate adaptor induced by hif-1, coordinates with the actions of cdk1/2 and pin1 to mediate hypoxia-induced pml proteasomal degradation.	SIGNOR-176033
O43156	P68400	0	phosphorylation	down-regulates	0.2	Here we report that tel2 and tti1 are targeted for degradation within mtorc1 by the scffbxo9 ubiquitin ligase to adjust mtor signalling to growth factor availability. This process is primed by ck2, which translocates to the cytoplasm to mediate mtorc1-specific phosphorylation of tel2/tti1	SIGNOR-200240
Q9UBE8	Q92793	1	phosphorylation	up-regulates activity	0.557	In vitro kinase assay showed that NLK could phosphorylate the C-terminal domain of CBP.	SIGNOR-280048
P35968	P23467	0	dephosphorylation	down-regulates activity	0.454	VE-PTP/VEGFR2 complex formation resumes with time, leading to dephosphorylation and deactivation of VEGFR2 (right). B) In VE-PTP-deficient cells, such as after siRNA treatment, VEGFR2 activation (middle) is exaggerated, leading to increased phosphorylation at the Y951 and Y1175 phosphorylation sites	SIGNOR-248441
P40763	Q13188	0	phosphorylation	down-regulates activity	0.2	Hippo pathway component MST2 kinase phosphorylates STAT3 at T622, which is located in the SH2 domain of STAT3. This phosphorylation blocks the SH2 domain in one STAT3 molecule to bind with the phosphorylated Y705 site in another STAT3 molecule, which further counteracts IL6-induced STAT3 dimerization and activation.	SIGNOR-277599
Q12778	Q96EB6	0	deacetylation	down-regulates quantity by destabilization	0.81	SIRT1 overexpression reduces muscle wasting by blocking the activation of FoxO1 and 3	SIGNOR-217975
P05156	P01024	1	cleavage	down-regulates activity	0.878	FH also serves as cofactor for the serine protease factor I (FI) that cleaves C3b into iC3b, unable to form C3 convertase (Fig 1B).	SIGNOR-263489
P10914	Q03001	1	transcriptional regulation	down-regulates quantity by repression	0.2	Transient transfection studies with BPAG1 promoter-luciferase reporter gene plasmids and IRF1 and IRF2 expression plasmids revealed that IRF1 and IRF2 directly down-regulated BPAG1 gene transcription in cultured normal human epidermal keratinocytes.	SIGNOR-254492
P08151	Q13547	0	deacetylation	up-regulates activity	0.594	Here, we identify a mechanism whereby Hh signalling is regulated, in which acetylation of Gli1 at Lys 518 represents a transcriptional inhibitory switch, while its HDAC1-mediated deacetylation is responsible for transcriptional activation.	SIGNOR-253544
P42229	P52333	0	phosphorylation	up-regulates	0.854	For these assays, coexpression of wt jak3 with stat5a was found to result in tyrosine phosphorylation of stat5a (lane 2) mediated by jak3, since stat5a coexpressed with the kinase-inactive k855a mutant form of jak3 was not tyrosine phosphorylated.	SIGNOR-182817
Q5XX13	P04406	1	polyubiquitination	up-regulates activity	0.2	Mechanistically, FBXW10 promotes GAPDH polyubiquitination and activation; VRK2-dependent phosphorylation of GAPDH Ser151 residue is critical for GAPDH ubiquitination and activation.	SIGNOR-277841
Q6R327	P49840	0	phosphorylation	down-regulates quantity by destabilization	0.387	We show that this process is dependent on glycogen synthase kinase 3 (GSK3): GSK3 was associated with rictor and directly phosphorylated the Thr-1695 site in a putative CDC4 phospho-degron motif of rictor; mutation of this site impaired the interaction between rictor and FBXW7, decreased rictor ubiquitination, and increased rictor stability.	SIGNOR-276899
Q15418	P62753	1	phosphorylation	up-regulates	0.589	We demonstrate that while ribosomal s6 kinase 1 (s6k1) phosphorylates rps6 at all sites, rsk exclusively phosphorylates rps6 at ser(235/236) in vitro and in vivo using an mtor-independent mechanism.	SIGNOR-153622
P31749	Q07812	1	phosphorylation	down-regulates activity	0.486	Phosphorylation of Bax Ser184 by Akt regulates its activity and apoptosis in neutrophilsWe suggest that Bax is regulated by phosphorylation of Ser(184) in an Akt-dependent manner and that phosphorylation inhibits Bax effects on the mitochondria by maintaining the protein in the cytoplasm, heterodimerized with antiapoptotic Bcl-2 family members	SIGNOR-252538
Q13094	P06241	0	phosphorylation	down-regulates	0.755	P59fyn_phosphorylated slp-76 at intermediate levels but, significantly, this phosphorylation failed to induce vav?SLP-76 complex formation	SIGNOR-46851
P24941	Q9UGP5	1	phosphorylation	up-regulates quantity by stabilization	0.335	Phosphorylation of DNA polymerase λ is required to maintain its stability. Recently, we identified Pol lambda as an interaction partner of cyclin-dependent kinase 2 (CDK2) that is central to the cell cycle G1/S transition and S-phase progression. Experiments with phosphorylation-defective mutants suggest that phosphorylation of Thr 553 is important for maintaining Pol lambda stability, as it is targeted to the proteasomal degradation pathway through ubiquitination unless this residue is phosphorylated.	SIGNOR-276169
Q14790	P06493	0	phosphorylation	down-regulates	0.361	In this study, we demonstrate that procaspase-8 is phosphorylated in mitotic cells by cdk1na interference-mediated silencing of cyclin b1 or treatment with the cdk1 inhibitor ro-3306 enhances the fas-mediated activation and processing of procaspase-8 in mitotic cells/cyclin b1 on ser-387	SIGNOR-168446
Q8N100	Q12837	1	transcriptional regulation	up-regulates quantity by expression	0.474	Thus, these data suggest that the expression of Brn3b can be activated directly by Math5 and that it is also subject to positive feedback regulation by Brn3 proteins.	SIGNOR-261567
P29474	P17252	0	phosphorylation	down-regulates activity	0.3	The phosphorylation of both S617 and S635 have also been shown to promote increased eNOS-derived NO release (Michell et al., 2002). The phosphorylaiton of S617 can be induced by PKA or Akt activity, and may serve to sensitize eNOS to calmodulin binding and modulate the phosphorylation of other eNOS sites	SIGNOR-251620
P78536	Q16539	0	phosphorylation	up-regulates activity	0.405	We show that p38 MAP kinase, which is activated in response to inflammatory or stress signals, directly activates TACE, a membrane-associated metalloprotease that is also known as ADAM17 and effects shedding in response to growth factors and Erk MAP kinase activation. p38alpha MAP kinase interacts with the cytoplasmic domain of TACE and phosphorylates it on Thr(735), which is required for TACE-mediated ectodomain shedding	SIGNOR-163970
Q8IX90	Q96GD4	0	phosphorylation	up-regulates activity	0.455	Aurora B directly phosphorylated Ska1 and Ska3 in vitro, and expression of phosphomimetic mutants of Ska1 and Ska3 impaired Ska KT recruitment and formation of stable KT-MT fibers (K-fibers), disrupting mitotic progression. We propose that Aurora B phosphorylation antagonizes the interaction between the Ska complex and the KMN network, thereby controlling Ska recruitment to KTs and stabilization of KT-MT attachments.	SIGNOR-262661
Q13976	P13569	1	phosphorylation	up-regulates	0.506	Direct amino acid sequencing and peptide mapping of cf-2 revealed that serines 660, 700, 737, and 813 as well as serine 768, serine 795, or both were phosphorylated by pka and pkgcftr possesses a large cluster of strict dibasic consensus sites for phosphorylation by protein kinase a (pka) in the r-domain and an obligatory dependence on phosphorylation is a hallmark of cftr cl(-) channel function	SIGNOR-18249
O43524	O14920	0	phosphorylation	down-regulates	0.692	Ikkbeta phosphorylates foxo3a at ser644. Ikappab kinase (ikk) physically interacts with, phosphorylates, and inhibits foxo3a independent of akt and causes proteolysis of foxo3a via the ub-dependent proteasome pathway	SIGNOR-124207
P17612	P35240	1	phosphorylation	up-regulates	0.405	Merlin contains a c-terminal serine 518, which is phosphorylated both by p21-activated kinase (pak) and protein kinase a (pka) (shaw et al., 2001;kissil et al., 2002;xiao et al., 2002;alfthan et al., 2004). Phosphorylation at this site is predicted to result in a more open conformation incapable of inhibiting cell growth,	SIGNOR-159840
P42336	Q13188	0	phosphorylation	down-regulates activity	0.2	MST1/2 and HGK inhibit catalytic activity of p110α through phosphorylation at T1061	SIGNOR-277922
Q13627	P10636	1	phosphorylation	down-regulates	0.427	Dyrk1a phosphorylates tau at least at s202, t212 and s404, but t212 phosphorylation is known to initiate tau hyperphosphorylation by gsk3b (ryoo et al., 2007;woods et al., 2001) and has been demonstrated to have a role in alternative splicing of taumrna	SIGNOR-171030
P25490	P07947	0	phosphorylation	down-regulates activity	0.2	YY1 phosphorylation is mediated by Src family kinases.	SIGNOR-276941
P46937	P42685	0	phosphorylation	down-regulates quantity by destabilization	0.275	Mechanistically, FRK interacted with and phosphorylated YAP on Tyr391/407/444, which recruited the classical E3 ubiquitin ligase Siah1 to catalyze ubiquitination and eventually degradation of YAP.	SIGNOR-275456

P35968

P17706

0

dephosphorylation

down-regulates activity

0.566

We show that a TCPTP substrate-trapping mutant interacts with VEGFR2. Moreover, TCPTP dephosphorylates VEGFR2 in a phosphosite-specific manner, inhibits its kinase activity and prevents its internalization from the cell surface. |The autophosphorylation sites Tyr1054/1059 and Tyr1214 were dephosphorylated by TCPTP (Fig. 4B). Tyr996, the functional significance of which is currently uncertain (Olsson et al., 2006), was a TCPTP target as well.

SIGNOR-248399

Q7Z2K8

P51608

0

post transcriptional regulation

up-regulates quantity by expression

0.298

MeCP2 binds to the promoter region of six target genes. ChIP with anti-MeCP2 antibody shows that MeCP2 binds to the promoter regions of activated targets Sst, Oprk1, Gamt, and Gprin1, and repressed targets Mef2c and A2bp1.

SIGNOR-264679

Q9BXM7

O75439

0

cleavage

down-regulates quantity by destabilization

0.339

Using an unbiased RNA-mediated interference (RNAi)-based screen, we identified four mitochondrial proteases, mitochondrial processing peptidase (MPP), presenilin-associated rhomboid-like protease (PARL), m-AAA and ClpXP, involved in PINK1 degradation. We find that PINK1 turnover is particularly sensitive to even modest reductions in MPP levels. Moreover, PINK1 cleavage by MPP is coupled to import such that reducing MPP activity induces PINK1 accumulation at the mitochondrial surface, leading to Parkin recruitment and mitophagy.

SIGNOR-261363

P68400

P11413

1

phosphorylation

up-regulates activity

0.2

CK2 phosphorylates G6PD T145 under ionizing radiation

SIGNOR-277890

Q00535

P10636

1

phosphorylation

down-regulates activity

0.763

We found that cdk5 phosphorylated tau(441) at Thr-181, Ser-199, Ser-202, Thr-205, Thr-212, Ser-214, Thr-217, Thr-231, Ser-235, Ser-396, and Ser-404, but not at Ser-262, Ser-400, Thr-403, Ser-409, Ser-413, or Ser-422. GSK-3beta phosphorylated all the cdk5-catalyzed sites above except Ser-235.

SIGNOR-249321

Q9HBH9

P06730

1

phosphorylation

up-regulates

0.56

Inhibition of mammalian target of rapamycin induces phosphatidylinositol 3-kinase-dependent and mnk-mediated eukaryotic translation initiation factor 4e phosphorylation.Therefore, eif4e is considered a survival protein involved in cell cycle progression, cell transformation, and apoptotic resistance. Phosphorylation of eif4e (usually at ser209) increases its binding affinity for the cap of mrna and may also favor its entry into initiation complexes.

SIGNOR-157537

Q13315

P15927

1

phosphorylation

up-regulates

0.809

Replication protein a (rpa) is a single-stranded dna (ssdna) binding protein involved in various processes, including nucleotide excision repair and dna replication. The 32 kda subunit of rpa (rpa32) is phosphorylated in response to various dna-damaging agents, and two protein kinases, ataxia-telangiectasia mutated (atm) and the dna-dependent protein kinase (dna-pk) have been implicated in dna damage-induced phosphorylation of rpa32we show that both dna-pk and atm phosphorylate rpa32 on thr21 in vitro.

SIGNOR-121861

Q14686

Q4ZG55

1

transcriptional regulation

up-regulates quantity by expression

0.2

Herein, using growth-regulating estrogen receptor binding 1 (GREB1) as an ERα target gene in Ishikawa cells, we demonstrate that nuclear receptor co-activator 6 (NCOA6) is essential for estradiol (E2)/ERα-activated GREB1 transcription. We found that NCOA6 associates with the GREB1 promoter and enhancer in an E2-independent manner and that NCOA6 knockout reduces chromatin looping, enhancer-promoter interactions, and basal GREB1 expression in the absence of E2.

SIGNOR-265883

Q12834

P53350

0

phosphorylation

down-regulates quantity by destabilization

0.977

Plk1 directly bound to Cdc20 and phosphorylates it on serine-170 located in CRY-box. Whereas wild-type Cdc20 was degraded according to progress cell cycle beyond mitosis, the phosphorylation-defective mutant, which serine-170 was changed into alanine, was not destroyed in early G1 phase.

SIGNOR-276493

P04406

Q13043

0

phosphorylation

up-regulates activity

0.279

Interestingly, GAPDH is phosphorylated by Mst1 to a comparable extent as its known substrate MBP, suggesting that GAPDH is a good substrate of Mst1 at least in vitro.|Moreover, interaction of Mst1 with GAPDH caused a robust phosphorylation of GAPDH and markedly increased the Mst1 activity in cells.

SIGNOR-279295

Q9GZV5

P07947

0

phosphorylation

up-regulates activity

0.317

Yes directly phosphorylates YAP and TAZ, resulting in their increased nuclear localization and transcriptional activity.Analysis by mass spectrometry identified Tyr391 and Tyr407 as the two phosphorylation sites of YAP, whereas Tyr305 was the sole phosphorylated residue of TAZ (Fig. 5F and fig. S4, A to C).

SIGNOR-277654

P68400

P54252

1

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

Q16611

P99999

1

relocalization

up-regulates

0.566

Allosteric activation of bak induces its intramembranous oligomerization into a proposed pore for cytochrome c efflux

SIGNOR-105206

P18031

P08581

1

dephosphorylation

down-regulates activity

0.637

It has been reported that the protein tyrosine phosphatase PTP1B could inactivate MET by direct dephosphorylation of Tyr 1234 and 1235 in its activation loop, and that this dephosphorylation takes place in peri-nuclear region of the cell [ xref ].

SIGNOR-277001

Q9Y4P1

P31749

0

phosphorylation

up-regulates activity

0.31

In this study, we identified a novel phosphorylation site at Ser34 of ATG4B induced by AKT in HCC cells.| In brief, our results demonstrate for the first time that the phosphorylation of ATG4B at Ser34 participates in the metabolic reprogramming of HCC cells via repressing mitochondrial function, which possibly results from the Ser34 phosphorylation-induced mitochondrial enrichment of ATG4B and the subsequent inhibition of F1Fo-ATP synthase activity.

SIGNOR-275834

P11388

P49841

0

phosphorylation

down-regulates quantity by destabilization

0.348

This study also reports the novel finding that topoIIα may be a target of GSK3β phosphorylation. Evidence suggests that CK2 serves as a priming kinase, through phosphorylation at Ser1365, for GSK3β-mediated phosphorylation at Ser1361.

SIGNOR-276301

Q5XPI4

P83916

1

polyubiquitination

down-regulates quantity by destabilization

0.2

In the present study, we report that HP1α and β undergo proteasomal degradation in lamin A/C knock-down cells and show by ectopic expression, RNAi and binding studies that the RING finger ubiquitin ligase RNF123 is directly involved in HP1 degradation.

SIGNOR-272034

O75475

O00311

0

phosphorylation

up-regulates

0.334

We now report identification of the cdc7-activator of s-phase kinase (ask) heterodimer as a novel interactor of ledgf. the kinase phosphorylated ledgf in vitro, with ser-206 being the major target, and ledgf phosphorylated at this residue could be detected during s phase of the cell cycle. Ledgf potently stimulated the enzymatic activity of cdc7-ask, increasing phosphorylation of mcm2 in vitro by more than 10-fold.

SIGNOR-25763

P01112

Q06124

0

dephosphorylation

up-regulates activity

0.681

Here we identify SHP2 as the ubiquitously expressed tyrosine phosphatase that preferentially binds to and dephosphorylates Ras to increase its association with Raf and activate downstream proliferative Ras/ERK/MAPK signalling.

SIGNOR-252094

Q9BZY9

Q96P20

1

ubiquitination

down-regulates quantity by destabilization

0.489

Taken together, these data indicated that TRIM31 directly induced the K48-linked ubiquitination of NLRP3 through its E3 ligase activity.|Taken together, these results indicated that TRIM31 could promote proteasomal degradation of NLRP3.

SIGNOR-278603

P35222

Q9Y297

0

ubiquitination

down-regulates

0.872

Here we show that fwd1 (the mouse homologue of slimb/betatrcp), an f-box/wd40-repeat protein, specifically formed a multi-molecular complex with beta-catenin, axin, gsk-3beta and apc. Mutations at the signal-induced phosphorylation site of beta-catenin inhibited its association with fwd1. Fwd1 facilitated ubiquitination and promoted degradation of beta-catenin, resulting in reduced cytoplasmic beta-catenin levels.

SIGNOR-67374

P07948

Q9NWQ8

1

phosphorylation

up-regulates activity

0.725

Here we show that Lyn interacts with C-terminal Src kinase-binding protein (Cbp), an adaptor protein that recruits negative regulators C-terminal Src kinase (Csk)/Csk-like protein-tyrosine kinase (Ctk). Lyn phosphorylated Cbp on several tyrosine residues, including Tyr314, which recruited Csk/Ctk to suppress Lyn kinase activity.Thus, a single phosphotyrosine residue on Cbp coordinates a two-phase process involving distinct negative regulatory pathways to inactivate, then degrade, Lyn.

SIGNOR-262898

P49841

Q9NX09

1

phosphorylation

down-regulates quantity by destabilization

0.339

It has been reported that GSK3beta phosphorylates REDD1 at residues Thr23 and Thr25, resulting in REDD1 recruitment to the Cullin 4a-beta-Trcp E3 ligase complex.

SIGNOR-279526

P11362

P0C6X7-PRO_0000037310

1

chemical inhibition

down-regulates activity

0.2

Pyrimidine 13 showed good potency against all the human VEGFR receptors with an IC50 of 10, 30, and 47 nM for VEGFR-1, -2, and -3, respectively. Significant activity was also seen against the closely related tyrosine receptor kinases PDGFRβ, c-Kit, FGF-R1, and c-fms with IC50’s of 84, 74, 140, and 146 nM, respectively.

SIGNOR-260150

Q99576

Q12778

1

relocalization

down-regulates activity

0.301

GILZ inhibits FOXO1, FOXO3, and FOXO4 transcriptional activities measured with natural or synthetic FOXO-responsive promoters in HL-60 cells.

SIGNOR-256146

P33316-2

P06493

0

phosphorylation

up-regulates quantity

0.386

DUTPase Is Phosphorylated at a Consensus Cyclin-dependent Protein Kinase Site: in Vitro Phosphorylation of Ser-11 by p34cdc2. It is conceivable that the exclusive phosphorylation of DUT-N may play a role in nuclear targeting of this protein. Taken a step further, Ser-11 may confer the ability of DUT-N to localize in specific regions of the nucleus where the dUTPase function is required. The Ser-11 Ala mutant should aid in the testing of these hypotheses.

SIGNOR-262693

P03372

P26045

0

dephosphorylation

up-regulates activity

0.2

Our recent studies further demonstrated that PTPH1 dephosphorylates estrogen receptor at Y537, increases estrogen receptor stability and nuclear accumulation, and enhances breast cancer sensitivity to anti-estrogens [ ].

SIGNOR-277127

P67775

P84022

1

dephosphorylation

down-regulates

0.2

Accordingly, smad3-associated pp2a activity was found under hypoxic conditions. Hypoxia attenuated the nuclear accumulation of tgf-beta-induced smad3 but did not affect smad2. Moreover, the influence of tgf-beta on a set of smad3-activated genes was attenuated by hypoxia, and this was reversed by chemical pp2a inhibition. Our data demonstrate the existence of a smad3-specific phosphatase and identify a novel role for pp2a.

SIGNOR-167480

Q99741

P53350

0

phosphorylation

up-regulates

0.566

Binding between cdc6 and plk1 occurs through the polo-box domain of plk1, and cdc6 is phosphorylated by plk1 on t37. These results suggest that plk1-mediated phosphorylation of cdc6 promotes the interaction of cdc6 and cdk1, leading to the attenuation of cdk1 activity, release of separase, and subsequent anaphase progression.

SIGNOR-169184

P01111

Q9Y397

0

palmitoylation

up-regulates activity

0.404

Covalent lipid modifications mediate the membrane attachment and biological activity of Ras proteins. All Ras isoforms are farnesylated and carboxyl-methylated at the terminal cysteine; H-Ras and N-Ras are further modified by palmitoylation. Here we report that H- and N-Ras are palmitoylated by a human protein palmitoyltransferase encoded by the ZDHHC9 and GCP16 genes. DHHC9 is an integral membrane protein that contains a DHHC cysteine-rich domain. GCP16 encodes a Golgi-localized membrane protein.

SIGNOR-261355

O94989

P60953

1

guanine nucleotide exchange factor

up-regulates activity

0.556

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-260541

P11309

Q92597

1

phosphorylation

down-regulates activity

0.2

Collectively, we find that PIM1 expression leads to increased levels of NDRG1 pS330, and PIM1 dependent NDRG1 phosphorylation decreases NDRG1 protein stability.|NDRG1 is phosphorylated by PIM1 at serine 330 (pS330), and the level of NDRG1 pS330 is associated higher grade prostate tumors.

SIGNOR-279308

P84022

Q9NYA4

0

dephosphorylation

down-regulates

0.517

Here we demonstrate that myotubularin-related protein 4

SIGNOR-163034

Q9NR80

P12931

0

phosphorylation

up-regulates

0.312

This observation strongly argues for the positive role of tyr94 phosphorylation in egf-induced asef activation following the activation of rac1.

SIGNOR-179601

Q9NQS7

P06493

0

phosphorylation

up-regulates

0.759

Here, we report that cdk1 phosphorylates thr 59 and thr 388 on inner centromere protein (incenp), which regulates the localization and kinase activity of aurora-b from prophase to metaphase. The replacement of endogenous incenp with t388a resulted in the delay of progression from metaphase to anaphase.

SIGNOR-143387

P06400

P06493

0

phosphorylation

down-regulates

0.688

The retinoblastoma gene product (prb) is a nuclear phosphoprotein that is thought to play a key role in the negative regulation of cellular proliferation. The active form of prb is underphosphorylated. Using synthetic peptides corresponding to potential cdc2 phosphorylation sites, we have developed a strategy which has allowed the identification of five sites. S249, t252, t373, s807 and s811 are phosphorylated in vivo, and in each case these sites correspond closely to the consensus sequence for phosphorylation by p34cdc2.

SIGNOR-21564

P27707

Q13315

0

phosphorylation

up-regulates activity

0.399

Here we report that ATM phosphorylation of dCK on Serine 74 is essential to activate the G2/M checkpoint in response to DNA damage.|Together, these results indicate that the dCK-Cdk1 interaction is enhanced in response to DNA damage and that ATM mediated dCK Serine 74 phosphorylation is required for the interaction.

SIGNOR-278221

P07948

Q96P20

1

phosphorylation

down-regulates

0.29

Lyn phosphorylates NLRP3 at Tyr 918 and controls NLRP3 ubiquitination.|Therefore, our data collectively indicate that Lyn inhibits the NLRP3 inflammasome in vivo.

SIGNOR-278485

P17252

Q13976

1

phosphorylation

up-regulates

0.344

Antibodies generated against phosphorylated threonine 58 were used to demonstrate phosphorylation in response to pma treatment of the cells with kinetics similar to vasodilator-stimulated phosphoprotein phosphorylation. A phospho-mimetic mutation at this site (t58e) generated a partially activated pkg that was more sensitive to cgmp levels. A phospho- mutation (t58a) revealed that this residue is important but not sufficient for pkg activation by pkc.

SIGNOR-98803

Q16539

P22415

1

phosphorylation

up-regulates activity

0.552

Following uv irradiation, usf-1 is phosphorylated by the p38 stress-activated kinase on threonine 153 and directly up-regulates expression of the pomc, mc1r, tyr, tyrp-1 and dct genes

SIGNOR-185572

Q16512

O15530

0

phosphorylation

up-regulates

0.567

It is shown that activation in vitro and in vivo involves the activation loop phosphorylation of prk1/2 by 3-phosphoinositide-dependent protein kinase-1 (pdk1) /pdk1 phosphorylates the prks at their conserved activation loop threonines (thr-774 and thr-816 for prk1 and prk2, respectively)

SIGNOR-76640

Q8IVA1

P35398

0

transcriptional regulation

up-regulates quantity by expression

0.2

RORα regulates the expression of several genes in Purkinje cells. RORα becomes highly expressed in postmitotic Purkinje cells. It regulates their maturation, particularly dendritic differentiation. Dendritogenesis and the expression of several genes, including Shh, Itpr1, Pcp4, Calb1, Pcp2, and Slc1a6, normally expressed in mature Purkinje cells, are inhibited in RORα-deficient mice.

SIGNOR-266849

Q9NX95

P33176

0

relocalization

up-regulates activity

0.56

Conventional kinesin I heavy chain binds to syntabulin and associates with syntabulin-linked syntaxin vesicles in vivo. These findings suggest that syntabulin functions as a linker molecule that attaches syntaxin-cargo vesicles to kinesin I, enabling the transport of syntaxin-1 to neuronal processes.

SIGNOR-264811

P68400

P51636

1

phosphorylation

up-regulates activity

0.32

We show that caveolin-2 is phosphorylated in vivo at two serine residues and that the phosphorylation of caveolin-2 is necessary for its actions as a positive regulator of caveolin-1 during organelle biogenesis in prostate cancer cells. Mutation of the primary phosphorylation sites on caveolin-2, serine 23 and 36, reduces the number of plasmalemma-attached caveolae

SIGNOR-101110

Q14938

P54756

1

transcriptional regulation

up-regulates quantity

0.2

For example, within the NFI targetome, we identified 6 collagen genes, 13 genes encoding potassium channel or glutamate receptor subunits and a range of factors related to axon guidance (e.g. Slit1, Robo1, Epha4, Epha5, Epha8)

SIGNOR-268909

Q9HAZ1

P00519

1

phosphorylation

down-regulates

0.272

Here, we identify clk1, clk4, mst1, mst2 and ttk (also known as mps1) as novel thr735 kinases in vitro / phosphorylation of thr735 in c-abl is critical for binding to 14-3-3

SIGNOR-181052

P49841

P24723

0

phosphorylation

down-regulates

0.2

Gsk3 is different from most kinases in that it is constitutively partially active and the most common regulatory mechanism is inhibition by phosphorylation of ser21 in gsk3_ or ser9 in gsk3_. This inhibitory phosphorylation can be mediated by several kinases, such as akt/protein kinase b (pkb), protein kinase c (pkc) and protein kinase a (pka).

SIGNOR-188585

P31749

Q92900

1

phosphorylation

up-regulates activity

0.257

AKT-Mediated UPF1 Phosphorylation at T151 Promotes UPF1 Helicase Activity

SIGNOR-277597

P31939

Q9UM73

0

phosphorylation

up-regulates activity

0.377

ATIC and VASP phosphorylation is dependent on NPM-ALK kinase activity. ATIC activity is enhanced in the presence of NPM-ALK in vitro.The ATIC activity is enhanced by NPM-ALK in HEK-293T-Rex cells.

SIGNOR-276171

O14757

Q13164

0

phosphorylation

up-regulates activity

0.276

Moreover, we demonstrate that ERK5 facilitates Chk1 phosphorylation induced by IR.|Since we have found that ERK5 was able to accelerate the phosphorylation and activation of IR-induced Chk1, therapeutic targeting of Chk1 in NSCLC cells with high ERK5 expression might be an effective strategy for overcoming radioresistance.

SIGNOR-280028

Q9NR96

Q9NWF9

0

ubiquitination

down-regulates quantity by destabilization

0.406

Here we describe how a RING finger protein, Triad3A, acts as an E3 ubiquitin-protein ligase and enhances ubiquitination and proteolytic degradation of some TLRs. Triad3A overexpression promoted substantial degradation of TLR4 and TLR9 with a concomitant decrease in signaling, but did not affect TLR2 expression or signaling.

SIGNOR-271505

P12931

Q15746

1

phosphorylation

up-regulates

0.417

Ec mlck-1 is phosphorylated by p60(src) on tyr(464) and tyr(471), resulting in a 2- to 3-fold increase in ec mlck-1 enzymatic activity.

SIGNOR-85009

O75688

P24941

1

dephosphorylation

down-regulates activity

0.362

CDK2 can be dephosphorylated and inactivated by protein phosphatase type 2C beta isoform long (PP2Cbetal), a unique phosphatase that was originally cloned from human liver.

SIGNOR-277153

A8MYZ6

Q13627

0

phosphorylation

down-regulates

0.305

Additionally, ck1, dyrk1a, and cdk2 also phosphorylate foxos at various sites to inhibit foxos activity

SIGNOR-183680

Q96KG7

P12931

0

phosphorylation

up-regulates activity

0.378

Our data suggest that c-Src augments the phosphorylation of MEGF10 and helps form a signaling complex.|These results indicate that overexpressed MEGF10 is phosphorylated by c-Src.

SIGNOR-279290

P17612

P16949

1

phosphorylation

down-regulates

0.309

Phosphorylation at either ser(16) or ser(63) strongly reduced or abolished the ability of stathmin to bind to and sequester soluble tubulin and its ability to act as a catastrophe factor by directly binding to the microtubules. The known in vivo phosphorylation sites of stathmin are ser-16 and ser-63 for cyclic amp-dependent protein kinase (pka).

SIGNOR-38318

O75676

P27361

0

phosphorylation

up-regulates

0.586

Rsk-b is a p38alphamapk substrate, and activated by p38alphamapk and, more weakly, by erk1

SIGNOR-60998

Q92830

Q5TEC6

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-269599

Q13555

P07101

1

phosphorylation

up-regulates activity

0.332

In both isoforms, Ser-40 was found to be phosphorylated by PKA, and Ser-19 and Ser-40 were found to be phosphorylated by CaM-PK II. The putative phosphorylation site generated by alternative splicing (Ser-31) was phosphorylated specifically by CaM-PK II in TH-2 only. | Unlike TH-1, phosphorylation of TH-2 by CaM-PK II resulted in an increase of the Ki value for dopamine.

SIGNOR-250709

Q9Y5Q3

P49841

0

phosphorylation

down-regulates

0.2

We showed that c-maf and mafb, like mafa, are indeed phosphorylated by gsk-3/ we demonstrated that phosphorylation by gsk-3 is conserved among the large maf proteins. It couples ubiquitination/degradation and transcriptional activation and modulates maf biological activity.

SIGNOR-159476

P12931

P54646

1

phosphorylation

down-regulates activity

0.258

We show here that Src signaling leads to direct phosphorylation of the AMPK-α subunit on a novel site, tyrosine 179, resulting in suppression of AMPK-T172 phosphorylation and autophagy upon integrin-mediated cell adhesion.

SIGNOR-277573

Q9NX47

P00441

1

ubiquitination

down-regulates quantity by destabilization

0.2

Mitochondrial ubiquitin ligase MITOL ubiquitinates mutant SOD1 and attenuates mutant SOD1-induced reactive oxygen species generation

SIGNOR-272982

O43524

O43638

0

transcriptional regulation

down-regulates quantity by repression

0.2

Fkhl18 suppressed the transcriptional activity of FoxO3a and FoxO4.

SIGNOR-261610

Q13371

P25098

0

phosphorylation

down-regulates activity

0.2

The phosphorylation of purified phosducin and PhLP by recombinant GRK2 proceeds rapidly and stoichiometrically (0.82 +/- 0.1 and 0.83 +/- 0.09 mol of P (i)/mol of protein, respectively).

SIGNOR-279178

Q14524

Q13554

0

phosphorylation

up-regulates activity

0.408

Among the sites identified, only six were previously suggested to be the targets for specific kinases using in silico and/or in vitro analyses: S36 and S525 were attributed to the regulation by PKA; S484 and S664 were assigned to the serum- and glucocorticoid-inducible kinase 3 (SGK3); and S516 and S571 were ascribed to CaMKII (reviewed in Marionneau and Abriel, 2015). In marked contrast, several previously described phosphorylation sites were not detected in the present study, including the PKA-dependent S528, the CaMKII-associated T594, the PKC-dependent S1506, the adenosine monophosphate–activated protein kinase (AMPK)–dependent T101 (Liu et al., 2019), and the six Fyn-dependent tyrosines (Ahern et al., 2005; Iqbal et al., 2018).|The simplest interpretation of these findings is that these three phosphorylation clusters, at positions S457-S460, S483-T486, and S664-S671, are likely involved in regulating the basal and/or gating properties of native cardiac NaV1.5 channels. Conversely, the other phosphorylation sites, with lower stoichiometries, may play spatially or temporally distinct roles in the physiological or more pathophysiological regulation of channel expression or gating. | Remarkably, this MS analysis also revealed that the vast majority of identified phosphorylation sites (at least 26) are clustered, suggesting concomitant phosphorylation and roles in regulating channel expression and/or function. Unexpectedly, however, except for S664, S667, and S671, no apparent effects of phosphomimetic or phosphosilent mutations were observed on heterologously expressed (in HEK-293 cells) NaV1.5

SIGNOR-275773

O14641

P48730

0

phosphorylation

up-regulates

0.534

Ck1_/__dependent phosphorylation of dvl2 at s143 and t224and that this event is critical to interact with plk1 in early stages of the cell cycle

SIGNOR-197547

P30566

Q96KS0

0

hydroxylation

up-regulates activity

0.2

ADSL is hydroxylated by EglN2 on Proline 24. An integrated transcriptomics and metabolomics analysis reveals that ADSL activates the oncogenic cMYC pathway by regulating cMYC protein level via a mechanism requiring ADSL proline 24 hydroxylation. ADSL regulates cMYC protein level through adenosine levels

SIGNOR-266613

Q05209

P52565

1

dephosphorylation

up-regulates activity

0.2

Integrin-bound PTP-PEST dephosphorylates RhoGDI1.|Translocation of Src phosphorylated RhoGDI1 to the cell 's leading edge promotes local activation of Rac1 and Cdc42, whereas dephosphorylation of RhoGDI1 by integrin bound PTP-PEST promotes RhoGDI1 release from the membrane and sequestration of inactive Rac1 and Cdc42 in the cytoplasm.|Translocation of Src-phosphorylated RhoGDI1 to the cell's leading edge promotes local activation of Rac1 and Cdc42, whereas dephosphorylation of RhoGDI1 by integrin-bound PTP-PEST promotes RhoGDI1 release from the membrane and sequestration of inactive Rac1/Cdc42 in the cytoplasm.

SIGNOR-277175

P08581

P18031

0

dephosphorylation

down-regulates activity

0.637

It has been reported that the protein tyrosine phosphatase PTP1B could inactivate MET by direct dephosphorylation of Tyr 1234 and 1235 in its activation loop, and that this dephosphorylation takes place in peri-nuclear region of the cell [ xref ].

SIGNOR-277001

P46527

O15355

0

dephosphorylation

up-regulates activity

0.2

By using genomic phosphatase screening, we identified a PPM family phosphatase, PPM1G, which could reduce p27 phosphorylation at T198.|Functionally, ectopic expression of PPM1G enhanced p27 protein stability and delayed cell cycle progression from G1 to S phase.

SIGNOR-277112

P30291

Q13153

0

phosphorylation

down-regulates

0.299

Kinases targeted sequentially to the neck, cla4/pak and cdc5/polo, are responsible for stepwise phosphorylation and down-regulation of swe1.

SIGNOR-123528

P24863

Q92585

0

relocalization

up-regulates

0.447

Cycc:cdk8 and cyct1:cdk9/p-tefb are recruited with notch and associated coactivators (mam, skip) to the hes1 promoter in signaling cells.

SIGNOR-130709

P06493

P29590

1

phosphorylation

down-regulates

0.345

Here, we show that klhl20, a cullin3 (cul3) substrate adaptor induced by hif-1, coordinates with the actions of cdk1/2 and pin1 to mediate hypoxia-induced pml proteasomal degradation.

SIGNOR-176033

O43156

P68400

0

phosphorylation

down-regulates

0.2

Here we report that tel2 and tti1 are targeted for degradation within mtorc1 by the scffbxo9 ubiquitin ligase to adjust mtor signalling to growth factor availability. This process is primed by ck2, which translocates to the cytoplasm to mediate mtorc1-specific phosphorylation of tel2/tti1

SIGNOR-200240

Q9UBE8

Q92793

1

phosphorylation

up-regulates activity

0.557

In vitro kinase assay showed that NLK could phosphorylate the C-terminal domain of CBP.

SIGNOR-280048

P35968

P23467

0

dephosphorylation

down-regulates activity

0.454

VE-PTP/VEGFR2 complex formation resumes with time, leading to dephosphorylation and deactivation of VEGFR2 (right). B) In VE-PTP-deficient cells, such as after siRNA treatment, VEGFR2 activation (middle) is exaggerated, leading to increased phosphorylation at the Y951 and Y1175 phosphorylation sites

SIGNOR-248441

P40763

Q13188

0

phosphorylation

down-regulates activity

0.2

Hippo pathway component MST2 kinase phosphorylates STAT3 at T622, which is located in the SH2 domain of STAT3. This phosphorylation blocks the SH2 domain in one STAT3 molecule to bind with the phosphorylated Y705 site in another STAT3 molecule, which further counteracts IL6-induced STAT3 dimerization and activation.

SIGNOR-277599

Q12778

Q96EB6

0

deacetylation

down-regulates quantity by destabilization

0.81

SIRT1 overexpression reduces muscle wasting by blocking the activation of FoxO1 and 3

SIGNOR-217975

P05156

P01024

1

cleavage

down-regulates activity

0.878

FH also serves as cofactor for the serine protease factor I (FI) that cleaves C3b into iC3b, unable to form C3 convertase (Fig 1B).

SIGNOR-263489

P10914

Q03001

1

transcriptional regulation

down-regulates quantity by repression

0.2

Transient transfection studies with BPAG1 promoter-luciferase reporter gene plasmids and IRF1 and IRF2 expression plasmids revealed that IRF1 and IRF2 directly down-regulated BPAG1 gene transcription in cultured normal human epidermal keratinocytes.

SIGNOR-254492

P08151

Q13547

0

deacetylation

up-regulates activity

0.594

Here, we identify a mechanism whereby Hh signalling is regulated, in which acetylation of Gli1 at Lys 518 represents a transcriptional inhibitory switch, while its HDAC1-mediated deacetylation is responsible for transcriptional activation.

SIGNOR-253544

P42229

P52333

0

phosphorylation

up-regulates

0.854

For these assays, coexpression of wt jak3 with stat5a was found to result in tyrosine phosphorylation of stat5a (lane 2) mediated by jak3, since stat5a coexpressed with the kinase-inactive k855a mutant form of jak3 was not tyrosine phosphorylated.

SIGNOR-182817

Q5XX13

P04406

1

polyubiquitination

up-regulates activity

0.2

Mechanistically, FBXW10 promotes GAPDH polyubiquitination and activation; VRK2-dependent phosphorylation of GAPDH Ser151 residue is critical for GAPDH ubiquitination and activation.

SIGNOR-277841

Q6R327

P49840

0

phosphorylation

down-regulates quantity by destabilization

0.387

We show that this process is dependent on glycogen synthase kinase 3 (GSK3): GSK3 was associated with rictor and directly phosphorylated the Thr-1695 site in a putative CDC4 phospho-degron motif of rictor; mutation of this site impaired the interaction between rictor and FBXW7, decreased rictor ubiquitination, and increased rictor stability.

SIGNOR-276899

Q15418

P62753

1

phosphorylation

up-regulates

0.589

We demonstrate that while ribosomal s6 kinase 1 (s6k1) phosphorylates rps6 at all sites, rsk exclusively phosphorylates rps6 at ser(235/236) in vitro and in vivo using an mtor-independent mechanism.

SIGNOR-153622

P31749

Q07812

1

phosphorylation

down-regulates activity

0.486

Phosphorylation of Bax Ser184 by Akt regulates its activity and apoptosis in neutrophilsWe suggest that Bax is regulated by phosphorylation of Ser(184) in an Akt-dependent manner and that phosphorylation inhibits Bax effects on the mitochondria by maintaining the protein in the cytoplasm, heterodimerized with antiapoptotic Bcl-2 family members

SIGNOR-252538

Q13094

P06241

0

phosphorylation

down-regulates

0.755

P59fyn_phosphorylated slp-76 at intermediate levels but, significantly, this phosphorylation failed to induce vav?SLP-76 complex formation

SIGNOR-46851

P24941

Q9UGP5

1

phosphorylation

up-regulates quantity by stabilization

0.335

Phosphorylation of DNA polymerase λ is required to maintain its stability. Recently, we identified Pol lambda as an interaction partner of cyclin-dependent kinase 2 (CDK2) that is central to the cell cycle G1/S transition and S-phase progression. Experiments with phosphorylation-defective mutants suggest that phosphorylation of Thr 553 is important for maintaining Pol lambda stability, as it is targeted to the proteasomal degradation pathway through ubiquitination unless this residue is phosphorylated.

SIGNOR-276169

Q14790

P06493

0

phosphorylation

down-regulates

0.361

In this study, we demonstrate that procaspase-8 is phosphorylated in mitotic cells by cdk1na interference-mediated silencing of cyclin b1 or treatment with the cdk1 inhibitor ro-3306 enhances the fas-mediated activation and processing of procaspase-8 in mitotic cells/cyclin b1 on ser-387

SIGNOR-168446

Q8N100

Q12837

1

transcriptional regulation

up-regulates quantity by expression

0.474

Thus, these data suggest that the expression of Brn3b can be activated directly by Math5 and that it is also subject to positive feedback regulation by Brn3 proteins.

SIGNOR-261567

P29474

P17252

0

phosphorylation

down-regulates activity

0.3

The phosphorylation of both S617 and S635 have also been shown to promote increased eNOS-derived NO release (Michell et al., 2002). The phosphorylaiton of S617 can be induced by PKA or Akt activity, and may serve to sensitize eNOS to calmodulin binding and modulate the phosphorylation of other eNOS sites

SIGNOR-251620

P78536

Q16539

0

phosphorylation

up-regulates activity

0.405

We show that p38 MAP kinase, which is activated in response to inflammatory or stress signals, directly activates TACE, a membrane-associated metalloprotease that is also known as ADAM17 and effects shedding in response to growth factors and Erk MAP kinase activation. p38alpha MAP kinase interacts with the cytoplasmic domain of TACE and phosphorylates it on Thr(735), which is required for TACE-mediated ectodomain shedding

SIGNOR-163970

Q8IX90

Q96GD4

0

phosphorylation

up-regulates activity

0.455

Aurora B directly phosphorylated Ska1 and Ska3 in vitro, and expression of phosphomimetic mutants of Ska1 and Ska3 impaired Ska KT recruitment and formation of stable KT-MT fibers (K-fibers), disrupting mitotic progression. We propose that Aurora B phosphorylation antagonizes the interaction between the Ska complex and the KMN network, thereby controlling Ska recruitment to KTs and stabilization of KT-MT attachments.

SIGNOR-262661

Q13976

P13569

1

phosphorylation

up-regulates

0.506

Direct amino acid sequencing and peptide mapping of cf-2 revealed that serines 660, 700, 737, and 813 as well as serine 768, serine 795, or both were phosphorylated by pka and pkgcftr possesses a large cluster of strict dibasic consensus sites for phosphorylation by protein kinase a (pka) in the r-domain and an obligatory dependence on phosphorylation is a hallmark of cftr cl(-) channel function

SIGNOR-18249

O43524

O14920

0

phosphorylation

down-regulates

0.692

Ikkbeta phosphorylates foxo3a at ser644. Ikappab kinase (ikk) physically interacts with, phosphorylates, and inhibits foxo3a independent of akt and causes proteolysis of foxo3a via the ub-dependent proteasome pathway

SIGNOR-124207

P17612

P35240

1

phosphorylation

up-regulates

0.405

Merlin contains a c-terminal serine 518, which is phosphorylated both by p21-activated kinase (pak) and protein kinase a (pka) (shaw et al., 2001;kissil et al., 2002;xiao et al., 2002;alfthan et al., 2004). Phosphorylation at this site is predicted to result in a more open conformation incapable of inhibiting cell growth,

SIGNOR-159840

P42336

Q13188

0

phosphorylation

down-regulates activity

0.2

MST1/2 and HGK inhibit catalytic activity of p110α through phosphorylation at T1061

SIGNOR-277922

Q13627

P10636

1

phosphorylation

down-regulates

0.427

Dyrk1a phosphorylates tau at least at s202, t212 and s404, but t212 phosphorylation is known to initiate tau hyperphosphorylation by gsk3b (ryoo et al., 2007;woods et al., 2001) and has been demonstrated to have a role in alternative splicing of taumrna

SIGNOR-171030

P25490

P07947

0

phosphorylation

down-regulates activity

0.2

YY1 phosphorylation is mediated by Src family kinases.

SIGNOR-276941

P46937

P42685

0

phosphorylation

down-regulates quantity by destabilization

0.275

Mechanistically, FRK interacted with and phosphorylated YAP on Tyr391/407/444, which recruited the classical E3 ubiquitin ligase Siah1 to catalyze ubiquitination and eventually degradation of YAP.

SIGNOR-275456