GleghornLab/Signor_2class · Datasets at Hugging Face

IdA string	IdB string	labels int64	mechanism string	effect string	score float64	sentence string	signor_id string
P28482	Q9BY84	1	phosphorylation	up-regulates quantity by stabilization	0.808	Phosphorylation of Ser-446 determines stability of MKP-7.\|We also determined that MKP-7 phosphorylated at Ser-446 has a longer half-life than unphosphorylated form of the wild type protein, as does a phospho-mimic mutant of MKP-7. These results indicate that activation of the ERK pathway strongly blocks JNK activation through stabilization of MKP-7 mediated by phosphorylation.	SIGNOR-249389
Q96A08	Q14493	0	translation regulation	up-regulates quantity by expression	0.2	Synthesis of mature histone mRNA requires only a single processing reaction: an endonucleolytic cleavage between a conserved stem-loop and a purine-rich downstream element to form the 3' end. The stem-loop binding protein (SLBP) is required for processing, and following processing, histone mRNA is transported to the cytoplasm, where SLBP participates in translation of the histone mRNA\|We used radiolabeled probes generated by PCR targeting the open reading frame (ORF) to detect histones H2A, H2B, H3, H4, and H1 and used 7SK snRNA as a loading control (Fig. 2A). The abundance of histone H2A, H2B, H3, and H4 mRNAs is reduced to 37% to 70% of control levels in the SLBP knockdown cells when compared to the C2 control.	SIGNOR-265393
O43464	Q16611	0	relocalization	up-regulates	0.295	Bax and/or bak-mediated release of pro-apoptotic mediators including smac/diablo and omi	SIGNOR-118908
P40763	P06239	0	phosphorylation	up-regulates activity	0.699	Lck was able to induce tyrosine phosphorylation of STAT3 to a level equal to or greater than that induced by Jak2.\|This finding, along with the previous data, gives strong evidence that Lck can directly and positively affect STAT3 activity.Our data provide strong evidence that Lck can activate STAT3 via phosphorylation in baculovirus infected insect cells.	SIGNOR-279201
P49137	Q7L5N7	1	phosphorylation	up-regulates activity	0.2	Mass spectrometry and mutagenesis analyses identified Ser34 of LPCAT2 as the phosphorylation site to enhance the catalytic activities. The experiments using inhibitors and siRNA against MAPK cascades demonstrated that LPCAT2 phosphorylation through LPS-TLR4 signaling may directly depend on MAPK-activated protein kinase 2 (MAPKAP kinase 2 or MK2).	SIGNOR-263077
O75874	A8MYZ6	0	transcriptional regulation	up-regulates quantity by expression	0.2	We identify FOXOs as transcriptional activators of IDH1. FOXOs promote IDH1 expression and thereby maintain the cytosolic levels of α-ketoglutarate and NADPH.	SIGNOR-260092
P19838	Q9Y297	0	polyubiquitination	down-regulates quantity by destabilization	0.589	Here we demonstrate that following IkappaB kinase (IkappaK)-mediated phosphorylation, the C-terminal domain of p105 (residues 918-934) serves as a recognition motif for the SCF(beta)(-TrCP) ubiquitin ligase.In vitro, SCF(beta)(-TrCP) specifically conjugates and promotes processing of phosphorylated p105.	SIGNOR-272570
Q86Y07	P29401	1	phosphorylation	up-regulates activity	0.2	Mechanistically, VRK2 promoted Thr287 phosphorylation of TKT and then recruited FBXL6 to promote TKT ubiquitination and activation.	SIGNOR-277842
P68400	Q8N5B7	1	phosphorylation	up-regulates activity	0.2	Most of the phosphorylated residues conformed to a consensus motif for phosphorylation by casein kinase 2 (CK2), and treatment of cells with the CK2-specific inhibitor CX-4945 lowered the phosphorylation levels of CERS2, -4, -5, and -6. Phosphorylation of CERS2 was especially important for its catalytic activity, acting mainly by increasing itsVmaxvalue.	SIGNOR-273987
P07550	P06213	0	phosphorylation	down-regulates activity	0.377	Insulin (10 nM)-stimulated rIR-catalyzed phosphorylation of β2-adrenergic receptor peptides was found prominently in peptides L339 (Tyr350 and Tyr354), T362 (Tyr364), and to a lesser extent peptides Y132 (Tyr132 and Tyr141), and I135 (Tyr141). G-protein-linked receptors and intrinsic tyrosine-kinase growth receptors represent two prominent modalities in cell signaling. Cross-regulation among members of both receptor superfamilies has been reported, including the counter-regulatory effects of insulin on β-adrenergic catecholamine action. Cells stimulated by insulin show loss of function and increased phosphotyrosine content of β2-adrenergic receptors.	SIGNOR-251302
P31749	Q15633	1	phosphorylation	up-regulates activity	0.2	We demonstrate that S6 kinases can phosphorylate the extended C-terminal domain of TRBP and interact with TRBP in situ in primary cells. TRBP serines 283/286 are essential for S6K-mediated TRBP phosphorylation, optimal expression of TRBP, and the S6K-TRBP interaction in human primary cells.	SIGNOR-274067
O15530	O43865	1	phosphorylation	down-regulates activity	0.2	Residue 68 resides in a consensus phosphorylation site for PKD (Figure 1A) [22,23]. Interestingly, phosphorylation of Ser68 could allow for subsequent phosphorylation of Ser71, Ser74, Ser77 and Ser80 by CK1, for which the consensus phosphorylation site is pS/T-X-X-S/T\| We found that phosphorylation of Ser71 and Ser74 were sufficient to enable inhibition of IP3 binding to the IP3R	SIGNOR-249174
P84022	O15105	0	transcriptional regulation	down-regulates quantity	0.613	The downstream molecules including mad2, smad3, smad4 and smad7 are involved in TGF-β1-induced EMT,while Smad7 blocks the smad3 expression	SIGNOR-260437
P19838	P50591	0	post transcriptional regulation	up-regulates quantity by expression	0.302	Treatment with TRAIL increased the NF-κB transcriptional activity by approximately twofold in MDA-MB-231 cells compared to the control.	SIGNOR-277936
O43257	Q16539	0	phosphorylation	up-regulates	0.314	We show that the srcap subunit named znhit1 or p18(hamlet), which is a substrate of p38 mapk, is recruited to the myogenin promoter at the onset of muscle differentiation, in a p38 mapk-dependent manner. Furthermore, p18hamlet was phosphorylated during myoblast differentiation in a p38 mapk-dependent manner (dal testo pmc)	SIGNOR-165571
P17706	P29353	1	dephosphorylation	down-regulates activity	0.572	However, TC45 inhibited the EGF-induced association of p52Shc with Grb2, which was attributed to the ability of the PTP to recognize specifically p52Shc phosphorylated on Y239. These results indicate that TC45 recognizes not only selected substrates in a cellular context but also specific sites within substrates and thus may regulate discrete signaling events.	SIGNOR-248397
O95239	Q13131	0	phosphorylation	up-regulates activity	0.2	We found that the strong direct substrate KIF4A is phosphorylated by AMPK at Ser801.Using in vitro kinase assays, we found that active AMPK and Aurora B phosphorylated KIF4A at Ser801 and Thr799 respectively in a time-dependent manner (Figure 5D). KIF4A is phosphoregulated by AMPK and Aurora B. Although AMPK phosphorylation increased the ATPase activity of KIF4A, Aurora B phosphorylation resulted in a stronger increase (Figure 5I), which might be consistent with the more powerful kinase function of Aurora B during mitosis.	SIGNOR-265991
Q13322	P27361	0	phosphorylation	up-regulates	0.298	Phosphorylation of grb10 by mitogen-activated protein kinase: identification of ser150 and ser476 of human grb10zeta as major phosphorylation sitesreplacing ser(150) and ser(476) with alanines reduced the inhibitory effect of human grb10zeta on insulin-stimulated irs1 tyrosine phosphorylation	SIGNOR-138171
Q96S59	Q13315	0	phosphorylation	up-regulates activity	0.439	We demonstrate that ATM phosphorylates RanBP9 in response to Ionizing Radiation and mediates its nuclear accumulation.	SIGNOR-279005
P67775	Q9UPZ9	1	dephosphorylation	down-regulates	0.2	In addition, mass spectrometry showed that pp2a treatment completely abolished the dually phosphorylated form, leaving only the singly phosphorylated form (data not shown). We conclude that a portion of ick in unstimulated and asynchronized hek293t cells is dually phosphorylated on the tdy motif.	SIGNOR-138432
P12931	P15514	1	cleavage	up-regulates	0.345	Ep2 can also promote the transactivation of epidermal growth factor receptor (egfr) expressed in colon cancer cells through src, which activates the proteolytic release of the egfr ligands amphiregulin (ar) and transforming growth factor-alfa (tgfalfa)125, thereby stimulating the egfr- network.	SIGNOR-236537
Q13464	P53671	1	phosphorylation	up-regulates	0.632	Specific activation of lim kinase 2 via phosphorylation of threonine 505 by rock, a rho-dependent protein kinase	SIGNOR-82755
P08237	Q8IYT8	0	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-274044
Q9H0M0	Q9Y2J4	1	ubiquitination	up-regulates activity	0.29	AMOTL2 mono-ubiquitination by WWP1 promotes contact inhibition by facilitating LATS activation\|Here, we provide evidence that the E3 ligase WWP1 (WW-domain containing protein 1) mono-ubiquitinates AMOTL2 (angiomotin-like 2) at K347 and K408.	SIGNOR-271873
P60510	P06493	1	dephosphorylation	down-regulates activity	0.397	PP4c efficiently dephosphorylates Cdk1 sites of NDEL1 but does not dephosphorylate the Aurora A site.\|We also found that PP4c negatively regulates Cdk1 activity in interphase.	SIGNOR-277162
Q7L0Q8	P12931	0	phosphorylation	down-regulates activity	0.534	Regulation of the Rho family small GTPase Wrch-1/RhoU by C-terminal tyrosine phosphorylation requires Src. Phosphorylation at Y254 negatively regulates Wrch-1-mediated biological functions.Serum-stimulated tyrosine phosphorylation and relocalization of Wrch-1 decreases its activation of downstream effectors in a Y254-dependent manner.	SIGNOR-259814
P07948	P11912	1	phosphorylation	up-regulates activity	0.738	Y182 of CD79a appears to be the initial and preferred site of Ag receptor phosphorylation by Src family kinases. In vitro, Src family Lyn and Fyn predominantly phosphorylate this residue in CD79a, and Y195 does so in CD79b. phosphorylation of Y182 alone can lead to further kinase activation and/or effector focusing necessary for phosphorylation of certain downstream targets, such as p62, p110, and Shc, but not others, such as Vav.	SIGNOR-251397
P17612	Q9GZU1	1	phosphorylation	down-regulates	0.2	The stimulatory effect of h89 on mcoln1 function was not observed when ser(557) and ser(559) were mutated to alanine residues, indicating that these two residues are essential for pka-mediated negative regulation of mcoln1.	SIGNOR-158946
O15111	Q9NQC7	1	phosphorylation	up-regulates activity	0.544	The phosphorylation of cyld was completely abolished by the combined mutations of the entire serine cluster (m4, lane 5). Similar results were obtained with the ikk holoenzyme (fig. 4c, panel 1), recombinant ikk_ (panel 2), and recombinant ikk_cyld phosphorylation may serve as a mechanism to inactivate its traf2 deubiquitination activity.	SIGNOR-204692
P30622	P68400	0	phosphorylation	up-regulates	0.293	Herein, we have identified polo-like kinase 1 (plk1) and casein kinase 2 (ck2) as two kinases of clip-170 and mapped s195 and s1318 as their respective phosphorylation sites.Plk1- and ck2-associated phosphorylations of clip-170 are involved in the timely formation of kinetochore-microtubule attachments in mitosis	SIGNOR-167168
O95863	Q15139	0	phosphorylation	down-regulates activity	0.466	Pkd1 phosphorylates ser(11) (s11) on transcription factor snail, a master emt regulator and repressor of e-cadherin expression, triggering nuclear export of snail via 14-3-3_ binding. Pkd1 regulates the expression of e-cadherin at the promoter level through direct phosphorylation of the transcriptional repressor snai1. Pkd1-mediated phosphorylation of snai1 occurs in the nucleus and generates a nuclear, inactive dna/snai1 complex that shows decreased interaction with its co-repressor ajuba.	SIGNOR-168537
Q9P0K8	Q9HC98	0	phosphorylation	up-regulates activity	0.2	Additionally, we found that NEK6 phosphorylated FOXJ2 at Thr23 and Ser254 ( xref , lanes 3 and 5), and NCOA5 at Ser21 and Ser151 ( xref , lanes 3 and 4).	SIGNOR-278965
Q76LX8	P04275	1	cleavage	down-regulates activity	0.599	Proteolytic degradation of VWF by ADAMTS-13 downregulates the proinflammatory potential of VWF.	SIGNOR-251966
P23443	O94763	1	phosphorylation	down-regulates activity	0.344	Here we report that the prefoldin chaperone URI represents a mitochondrial substrate of S6K1. In growth factor-deprived or rapamycin-treated cells, URI forms stable complexes with protein phosphatase (PP)1gamma at mitochondria, thereby inhibiting the activity of the bound enzyme. Growth factor stimulation induces disassembly of URI/PP1gamma complexes through S6K1-mediated phosphorylation of URI at serine 371.	SIGNOR-262943
P18846	P68400	0	phosphorylation	up-regulates	0.296	Camk ii phosphorylates only ser63 (corresponding to ser133 of creb), which is essential for the activation, and not ser72 (corresponding to ser142 of creb), which is a negative regulation site	SIGNOR-42565
P19525	P04637	1	phosphorylation	up-regulates	0.571	The double-stranded rna activated protein kinase pkr physically associates with the tumor suppressor p53 protein and phosphorylates human p53 on serine 392 in vitro.	SIGNOR-68033
P21731-2	P17252	0	phosphorylation	down-regulates activity	0.521	These data suggest a model whereby agonist-induced PKC phosphorylation of Ser(145) partially impairs TPbeta signalling while GRK2/3 phosphorylation at both Ser(239) and Ser(357) within its IC(3) and C-tail domains, respectively, sterically inhibits G-protein coupling, profoundly desensitizing signalling, and promotes beta-arrestin association and, in turn, facilitates TPbeta internalization.	SIGNOR-274092
P68400	P55010	1	phosphorylation	up-regulates	0.394	We find that eif5 is associated with ck2 when the kinase activity is at the highest level in vivo, and is phosphorylated at ser389 and ser390 by ck2.	SIGNOR-141159
Q12888	Q16539	0	phosphorylation	down-regulates activity	0.28	Here we show that 53BP1 is phosphorylated during mitosis on two residues, T1609 and S1618, located in its well-conserved ubiquitination-dependent recruitment (UDR) motif.\|Dephosphorylation enables the recruitment of 53BP1 to double-strand DNA breaks \|phosphorylation of T1609 is likely to be mediated by p38 MAPK	SIGNOR-264446
Q92570	P04637	0	transcriptional regulation	up-regulates quantity by expression	0.264	We showed that p53 directly bound the promoter of NR4A3 gene and induced its transcription. p53 transactivates the NR4A3 promoter in H1299 cells.	SIGNOR-256200
Q15759	Q06413	1	phosphorylation	up-regulates activity	0.538	In this study, we demonstrate that among the different Mitogen-activated protein kinases, the MADS-box transcription factors MEF2A and MEF2C are preferentially phosphorylated and activated by the p38 subfamily members p38alpha and p38beta2.	SIGNOR-280025
P31749	O75376	1	phosphorylation	down-regulates	0.424	Akt-induced phosphorylation of n-cor at serine 1450 contributes to its misfolded conformational dependent loss (mcdl) in acute myeloid leukemia of the m5 subtype.	SIGNOR-198913
P06493	P40337	1	phosphorylation	up-regulates activity	0.2	Mechanistically, CDK1 directly phosphorylates pVHL at Ser80, which primes the recognition of pVHL by PIN1.\|PIN1 and CDK1 cooperatively modulate the protein turnover of pVHL, thereby conferring tumor growth, chemotherapeutic resistance and metastasis both in vitro and in vivo.	SIGNOR-280207
Q12913	P35968	1	dephosphorylation	down-regulates	0.699	The autoactivation residues y1054 and y1059 are targeted by dep-1 and this results in the inhibition of kinase activity and the consequent general dephosphorylation of vegfr2.	SIGNOR-181672
P03372	P04626	0	phosphorylation	up-regulates	0.572	The results presented here show for the first time that er redistribution to the cytoplasm and its interaction with her2 are important downstream effects of her2 overexpression, that erk1/2 is important for er cytoplasmic localization, and that subcellular localization of er may play a mechanistic role in determining the responsiveness of breast cancer cells to tamoxifen.	SIGNOR-124962
P35580	Q06413	0	transcriptional regulation	up-regulates quantity by expression	0.345	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-238769
P02671	P39900	0	cleavage	down-regulates quantity by destabilization	0.2	Matrix metalloproteinases collagenase-2, macrophage elastase, collagenase-3, and membrane type 1-matrix metalloproteinase impair clotting by degradation of fibrinogen and factor XII\| We have now investigated the role of collagenase-2 (MMP-8), macrophage elastase (MMP-12), collagenase-3 (MMP-13), and membrane type 1-matrix metalloproteinase (MT1-MMP, MMP-14) in the degradation of fibrinogen and Factor XII of the plasma clotting system. \|Fibrinogen was subjected to MMP-cleavage, and the resulting fragments were isolated. The amino acid sequences were determined by automated Edman degradation.\|MMP-12 20ADSGEGD a-chain\| 540FVSETESRG a-chain\|433LVTSKGDK a-chain	SIGNOR-263622
Q13627	P46527	1	phosphorylation	up-regulates activity	0.332	DYRK1A phosphorylates p27 Kip1 at Ser10 in primary neurons and in vivo.\|Thus, our results identify DYRK1A as the predominant kinase that phosphorylates and stabilizes p27Kip1 during neuronal differentiation.	SIGNOR-278250
O14733	O43318	0	phosphorylation	up-regulates activity	0.645	Upon TNFα stimulation, MEKK1, ASK1, and TAK1 phosphorylate and activate MKK7, which in turn activates JNK	SIGNOR-274146
Q16512	P36871	1	phosphorylation	up-regulates	0.2	Pak1-mediated phosphorylation of pgm selectively on threonine 466 significantly increased pgm enzymatic activity	SIGNOR-128722
P51817	O43541	1	phosphorylation	up-regulates activity	0.431	In vitro phosphorylation assays demonstrated that PrKX phosphorylates Smad6 at a serine residue.	SIGNOR-279270
O95278	Q9UQK1	1	dephosphorylation	up-regulates quantity by stabilization	0.749	We have recently described that the activity of R5/PTG is down-regulated by the laforin-malin complex, composed of a dual specificity phosphatase (laforin) and an E3-ubiquitin ligase (malin). We now demonstrate that phosphorylation of R5/PTG at Ser-8 by AMPK accelerates its laforin/malin-dependent ubiquitination and subsequent proteasomal degradation, which results in a decrease of its glycogenic activity.	SIGNOR-276239
O14786	Q04741	0	transcriptional regulation	up-regulates quantity by expression	0.2	EMX1 activates the transcription of Nrp1 in vitro.	SIGNOR-261593
P43405	P29353	1	phosphorylation	up-regulates	0.762	The syk-family kinases (syk and zap-70) were able to phosphorylate the y239 and y240 sites, and less efficiently the y317 site on sch1 (iso2).	SIGNOR-59635
P45983	Q14934	1	phosphorylation	up-regulates activity	0.467	Here, we showed that the nuclear factor of activated T3 (NFAT3) is phosphorylated by JNK1 or JNK2 at Ser(213) and Ser(217), which are located in the conserved SP motif.\|Moreover, a 3xNFAT-luc reporter gene assay indicated that NFAT3 transcriptional activity was increased in a dose dependent manner by JNK1 or JNK2.	SIGNOR-280033
P61586	Q14192	1	relocalization	up-regulates	0.348	Here, we show that stimulation of the rho pathway induces translocation of the transcriptional lim-only coactivator fhl2 to the nucleus and subsequent activation of fhl2- and androgen receptor-dependent genes.	SIGNOR-114071
Q9NRC8	P84243	1	deacetylation	up-regulates activity	0.2	SIRT7 links H3K18 deacetylation to maintenance of oncogenic transformation.\|Genome-wide binding studies reveal that SIRT7 binds to promoters of a specific set of gene targets, where it deacetylates H3K18Ac and promotes transcriptional repression.	SIGNOR-275872
Q13480	P08581	0	phosphorylation	up-regulates activity	0.674	Gab-1 is phosphorylated on the same residues by HGF and EGF receptors. Among 16 peptides only nine were phosphorylated by the EGF and HGF receptors, namely peptides containing the tyrosine residues 285, 307, 373, 407, 448, 473, 590, 628 and 660. we show that in the response to HGF or EGF, Gab1 is phosphorylated in vivo on the same residues. However, a sustained activation of signaling pathways downstream to Gab1 (as a result of its sustained phosphorylation) is achieved only in response to HGF.	SIGNOR-250290
P16220	P51812	0	phosphorylation	up-regulates activity	0.726	MAPK activates CREB kinase, which in turn phosphorylates and activates CREB. Purification, sequencing, and biochemical characterization of CREB kinase revealed that it is identical to a member of the pp90(RSK) family, RSK2. RSK2 was shown to mediate growth factor induction of CREB serine-133 phosphorylation both in vitro and in vivo. These findings identify a cellular function for RSK2 and define a mechanism whereby growth factor signals mediated by RAS and MAPK are transmitted to the nucleus to activate gene expression	SIGNOR-248951
P27361	Q9HBH9	1	phosphorylation	up-regulates	0.517	Erk and p38 phosphorylate mnk1 and mnk2, which stimulates their in vitro kinase activity.	SIGNOR-48355
Q92630	Q13315	0	phosphorylation	up-regulates quantity by stabilization	0.558	ATM augments nuclear stabilization of DYRK2 by inhibiting MDM2 in the apoptotic response to DNA damage\|Upon exposure to genotoxic stress, ATM phosphorylates DYRK2 at Thr-33 and Ser-369, which enables DYRK2 to escape from degradation by dissociation from MDM2 and to induce the kinase activity toward p53 at Ser-46 in the nucleus.	SIGNOR-275577
P63000	O75962	0	guanine nucleotide exchange factor	up-regulates activity	0.692	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-260579
Q5VT25	P10916	1	phosphorylation	up-regulates activity	0.65	These approximately 190-kDa myotonic dystrophy kinase-related Cdc42-binding kinases (MRCKs) preferentially phosphorylate nonmuscle myosin light chain at serine 19, which is known to be crucial for activating actin-myosin contractility.	SIGNOR-250723
P06493	Q99459	1	phosphorylation	up-regulates activity	0.624	Cdc5-dependent Net1 phosphorylation and Cdc14 release from the nucleolus require prior Cdc5 activation by Cdk1 and active separase to promote Cdc14 activation.\|Cdk1 initially phosphorylates Cdc5, mostly at T242 and T238 (T242 phosphorylation is especially relevant based on our results), and phosphorylation activates its kinase activity, which is essential for anaphase progression.	SIGNOR-279597
Q16625	Q02156	0	phosphorylation	up-regulates	0.2	Thr403, thr404, thr424 and thr438 in the occludin c-terminal domain are the predominant sites of pkc_-dependent phosphorylation . The present study demonstrates that pkc_ phosphorylates occludin on specific threonine residues and promotes assembly of epithelial tight junctions.	SIGNOR-173643
P35637	P78352	1	post transcriptional regulation	up-regulates quantity	0.27	These results point toward a novel mechanism by which FUS targets neuronal mRNA and given that these PSD-95 and Shank1 3'-UTR G quadruplex structures are also targeted by the fragile X mental retardation protein (FMRP), they raise the possibility that FUS and FMRP might work together to regulate the translation of these neuronal mRNA targets.\|As seen in Figure 7 (top panel), both PSD-95 Q1-Q2 and Shank1a GQ probes pulled down endogenous FUS, whereas their M2 mutants did not, indicating that the GQ structure is sufficient for recognition.	SIGNOR-262103
P68400	P0DP23	1	phosphorylation	down-regulates activity	0.422	Phosphorylation of CaM at four sites by CK2 was found to follow a sequential order, with Ser81 as the first, Thr79 as the second, and Ser101 or Thr117 as the third.	SIGNOR-266355
Q92626	P53420	1	catalytic activity	up-regulates quantity by stabilization	0.256	Peroxidasin (PXDN), an ECM protein with peroxidase activity, is integral to basement membrane consolidation through catalysis of sulfilimine bonds in collagen IV. PXDN has been shown to form dityrosine crosslinks and also catalyses sulfilimine bonds, in the presence of hypohalous acids, to connect collagen IV protomers, which are an integral component of the basement membrane	SIGNOR-265250
Q9Y4P1	Q99942	0	ubiquitination	down-regulates quantity by destabilization	0.405	These results substantiate the notion that RNF5 negatively regulates ATG4B availability with concomitant effect on LC3 processing and autophagy under normal growth conditions.\|These results suggest that RNF5 directly induces ATG4B ubiquitination.	SIGNOR-278664
Q9UHD2	P35813	0	dephosphorylation	down-regulates activity	0.41	Furthermore, PPM1A, but not PPM1B, serves as an efficient phosphatase to dephosphorylate Ser 172 residue of both TBK1 and IKKepsilon kinases, which is critical for their kinase activities.\|In a similar in vitro phosphatase assay, incubation of PPM1A also eliminated TBK1 and IKKepsilon phosphorylation at Ser 172 residue, evidenced by phospho-S172 immunoblotting (XREF_FIG, F and G).\|These observations suggest that PPM1A may block kinase activities of TBK1 and IKKepsilon.	SIGNOR-276966
P08254	Q99075	1	cleavage	up-regulates	0.517	It was concluded that mmp-3 cleaves hb-egf at a specific site in the jm domain and that this enzyme might regulate the conversion of hb-egf from being a juxtacrine to a paracrine/autocrine growth factor.	SIGNOR-83339
Q8WU20	P22681	0	ubiquitination	down-regulates	0.576	The experiments presented in this report illustrate that in response to fgf stimulation, cbl is recruited by grb2 binding to the frs2_ multiprotein complex, resulting in ubiquitination of frs2_ and fgfr. grb2 functions as a link between frs2_ and cbl;grb2 is bound to tyrosine-phosphorylated frs2_ by means of its sh2 domain and to a proline-rich region in the c terminus of cbl by means of its sh3 domains.	SIGNOR-87166
P46527	Q00535	0	phosphorylation	down-regulates activity	0.643	CDK5 knockdown in HEY cells significantly prolonged the half-life of TP53 and p27 Kip1 proteins (XREF_FIG).\|During neural stem cell differentiation, CDK5 can phosphorylate p27 at Thr187 and at Ser10, promoting neurite outgrowth as neurons differentiate .	SIGNOR-279681
O14746	P06493	0	phosphorylation	up-regulates activity	0.324	Here we report that hTERT is phosphorylated at threonine 249 during mitosis by the serine/threonine kinase CDK1.These observations indicate that phosphorylation at threonine 249 regulates hTERT RdRP and contributes to cancer progression in a telomere independent manner.	SIGNOR-277517
Q15717	O14672	1	post transcriptional regulation	up-regulates quantity	0.2	Neuronal ELAV (nELAV) proteins are RNA-binding proteins which play a physiological role in controlling gene expression in memory formation, and their alteration may contribute to cognitive impairment associated with neurodegenerative pathologies such as Alzheimer's disease (AD). The experiments show for the first time that ADAM10mRNA represents a nELAV target and that these RNA-binding proteins can play a role in the post-transcriptional regulation of ADAM10 expression. nELAV proteins specifically bind the ADAM10 mRNA and this binding is disrupted following Aβ exposure	SIGNOR-266862
P17252	P28329	1	phosphorylation	up-regulates	0.383	We show that chat is differentially phosphorylated by protein kinase c (pkc) isoforms on four serines (ser-440, ser-346, ser-347, and ser-476) and one threonine (thr-255). This phosphorylation is hierarchical, with phosphorylation at ser-476 required for phosphorylation at other serines. Phosphorylation at some, but not all, sites regulates basal catalysis and activation.	SIGNOR-129264
P36508	P17987	1	transcriptional regulation	up-regulates quantity by expression	0.347	The transcription from the minimalCcta promoter was up-regulated 3-fold by ZNF143 and 6-fold by ZNF76 when full-length proteins were co-expressed, indicating that both ZNF143 and ZNF76 can enhance Ccta transcription.	SIGNOR-266221
Q14114	P06241	0	phosphorylation	up-regulates quantity	0.635	Fyn phosphorylates ApoER2.\|Together these data demonstrate that Fyn activity is necessary for its effects increasing ApoER2 levels.	SIGNOR-278197
P49841	O95863	1	phosphorylation	down-regulates	0.557	Snail is a well-known zn-finger transcription factor that promotes emt by repressing e-cadherin expression. It is known that snail is phosphorylated by gsk3beta and degraded by beta-trcp-mediated ubiquitination. A variant of snail (snail-6sa), which abolishes these phosphorylations, is much more stable and resides exclusively in the nucleus to induce emt	SIGNOR-129402
P63279	P59595	1	sumoylation	up-regulates activity	0.2	In this study, we identified Ubc9 as a host protein that interacts specifically with SARS-CoV N protein. This interaction was verified both in vivo and in vitro. Furthermore, we showed that, in addition to phosphorylation, the N protein was modified by covalent attachment of SUMO to its lysine 62 residue. Evidence provided demonstrated that sumoylation may promote homo-oligomerization of the protein.	SIGNOR-260263
Q9Y2X7	P12931	0	phosphorylation	up-regulates activity	0.542	Tyrosines 246 and 293 are required to hold GIT1 in a closed conformation.Hyperphosphorylation of GIT1-N by Src and pervanadate does not affect its binding in vitro to full length GIT1 proteins. Mutations Y246E and Y293E of GIT1 enhance binding to paxillin.	SIGNOR-276627
O14757	P84243	1	phosphorylation	down-regulates activity	0.2	We identify chk1 as the kinase responsible for h3-t11 phosphorylation. H3-t11 phosphorylation occurs throughout the cell cycle and is chk1 dependent in vivo.Phosphorylation at thr-12 (h3t11ph) by pkn1 is a specific tag for epigenetic transcriptional activation that promotes demethylation of lys-10 (h3k9me) by kdm4c/jmjd2c.	SIGNOR-160557
P50542	Q13315	0	phosphorylation	up-regulates activity	0.497	Specificity for autophagy of peroxisomes (pexophagy) is provided by ATM phosphorylation of PEX5 at Ser 141, which promotes PEX5 monoubiquitylation at Lys 209, and recognition of ubiquitylated PEX5 by the autophagy adaptor protein p62, directing the autophagosome to peroxisomes to induce pexophagy.	SIGNOR-262792
Q9UBN7	P00533	0	phosphorylation	down-regulates	0.44	A negative feedback loop consisting of egfr-mediated phosphorylation of hdac6 tyr(570) resulted in reduced deacetylase activity and increased acetylation of alpha-tubulin.	SIGNOR-162431
P35222	Q9P289	0	phosphorylation	up-regulates quantity by stabilization	0.2	In response to Wnt3a stimulation, the kinase MST4 directly phosphorylates \u03b2-catenin at Thr40 to block its Ser33 phosphorylation by GSK3\u03b2.	SIGNOR-280141
P25445	Q9NP71	0	transcriptional regulation	up-regulates quantity by expression	0.2	The present study provides evidence for a direct and dominant role of ChREBP in the glucose regulation of two key liver lipogenic enzymes, acetyl-CoA carboxylase (ACC) and fatty acid synthase (FAS)	SIGNOR-267947
O15524	O60674	1	ubiquitination	down-regulates quantity by destabilization	0.795	Shp-2 regulates socs-1-mediated janus kinase-2 ubiquitination/degradation downstream of the prolactin receptor	SIGNOR-118407
P68431	Q7LBC6	0	demethylation	down-regulates activity	0.2	We have purified a JmjC domain-containing protein, JHDM2A, which specifically demethylates mono- and dimethyl-H3K9. JHDM2A exhibits hormone-dependent recruitment to androgen-receptor target genes, resulting in H3K9 demethylation and transcriptional activation. Thus, our work identifies a histone demethylase and links its function to hormone-dependent transcriptional activation.	SIGNOR-266634
P49841	Q99250	1	phosphorylation	down-regulates activity	0.2	Glycogen synthase kinase 3β (GSK3beta) phosphorylates the Nav1.2C-terminal tail at T1966, suppressing Na+ currents and channel trafficking to the plasma membrane	SIGNOR-275748
O15033	O43236	1	ubiquitination	down-regulates quantity by destabilization	0.2	Furthermore, the ubiquitination and degradation of SMAC, HtrA2, and ARTS were significantly enhanced in AREL1-expressing cells following apoptotic stimulation, indicating that AREL1 binds to and ubiquitinates cytosolic but not mitochondria-associated forms of IAP antagonists	SIGNOR-267670
P61586	O60890	0	gtpase-activating protein	up-regulates activity	0.636	OPHN-1 colocalized with the actin cytoskeleton in neuronal and glial cells. We have previously shown that OPHN1 stimulates GTPases activity of RhoA, Cdc42, and Rac1 in vitro	SIGNOR-268397
P60953	A1L390	0	guanine nucleotide exchange factor	up-regulates activity	0.354	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-260585
P46937	P48730	0	phosphorylation	down-regulates	0.421	LATS1/2-mediated phosphorylation of a conserved serine in this region (Ser311 in human TAZ; Ser397 in human YAP) primes for further phosphorylation by CK1_/_ kinases (Ser314 on human TAZ; Ser400/403 in human YAP)	SIGNOR-230738
P68400	O95863	1	phosphorylation	up-regulates quantity by stabilization	0.348	Serines 11 and 92 participate in the control of snail1 stability and positively regulate snail1 repressive function and its interaction with msin3a corepressor. Furthermore, serines 11 and 92 are required for snail1-mediated emt and cell viability, respectively. Pka and ck2 have been characterized as the main kinases responsible for in vitro snail1 phosphorylation at serine 11 and 92, respectively.	SIGNOR-161771
Q8IVP5	P68400	0	phosphorylation	down-regulates activity	0.427	Here, we identify that the mitochondrially localized PGAM5 phosphatase interacts with and dephosphorylates FUNDC1 at serine 13 (Ser-13) upon hypoxia or carbonylcyanide p-trifluoromethoxyphenylhydrazone (FCCP) treatment. Dephosphorylation of FUNDC1 catalyzed by PGAM5 enhances its interaction with LC3, which is abrogated following knockdown of PGAM5 or the introduction of a cell-permeable unphosphorylated peptide encompassing the Ser-13 and LIR of FUNDC1. We further observed that CK2 phosphorylates FUNDC1 to reverse the effect of PGAM5 in mitophagy activation.	SIGNOR-273622
Q9NP58	Q16236	0	transcriptional regulation	up-regulates quantity by expression	0.2	NFE2L2 is stabilized and translocates to the nucleus, where it dimerizes with sMAF proteins. This complex binds to AREs to mediate the transcription of genes involved in iron metabolism, GSH metabolism, and ROS detoxification.Two critical enzymes in this pathway, ATP binding cassette subfamily B member 6 (ABCB6) and ferrochelatase (FECH), are regulated by the transcription factor NFE2L2 and play significant roles in inhibiting ferroptosis when upregulated.	SIGNOR-279864
P67775	P19429	1	dephosphorylation	down-regulates	0.401	The major phosphatase thought to dephosphorylate ctni and phospholamban is type 2a protein phosphatase (pp2a) [61]. Activation of pp2a and ensuing dephosphorylation of regulatory proteins is involved in the anti-adrenergic effects of adenosine and muscarinic receptor activation see also fig2.	SIGNOR-134601
Q16584	P45985	1	phosphorylation	up-regulates	0.625	These data suggest that mlk-3 phosphorylates sek1 directly and that it does so specifically on those residues known to activate sek1 in vivo.	SIGNOR-75836
P53355	O95786	1	phosphorylation	down-regulates activity	0.33	DAPK1 also phosphorylates the N-terminal serine at position 8 (S8) of RIG-I, which is also reported to undergo phosphorylation by PKC-\u03b1/\u03b2 to suppress TRIM25-mediated RIG-I ubiquitination, thereby negatively regulating RIG-I activity (84).	SIGNOR-279519
O15273	Q9UKT6	0	ubiquitination	down-regulates quantity by destabilization	0.2	FBXL21 is a clock-controlled E3 ligase modulating circadian periodicity via subcellular-specific CRYPTOCHROME degradation. How FBXL21 regulates tissue-specific circadian physiology and what mechanism operates upstream is poorly understood. Here we report the sarcomere component TCAP as a cytoplasmic substrate of FBXL21.	SIGNOR-264853

P28482

Q9BY84

1

phosphorylation

up-regulates quantity by stabilization

0.808

Phosphorylation of Ser-446 determines stability of MKP-7.|We also determined that MKP-7 phosphorylated at Ser-446 has a longer half-life than unphosphorylated form of the wild type protein, as does a phospho-mimic mutant of MKP-7. These results indicate that activation of the ERK pathway strongly blocks JNK activation through stabilization of MKP-7 mediated by phosphorylation.

SIGNOR-249389

Q96A08

Q14493

0

translation regulation

up-regulates quantity by expression

0.2

Synthesis of mature histone mRNA requires only a single processing reaction: an endonucleolytic cleavage between a conserved stem-loop and a purine-rich downstream element to form the 3' end. The stem-loop binding protein (SLBP) is required for processing, and following processing, histone mRNA is transported to the cytoplasm, where SLBP participates in translation of the histone mRNA|We used radiolabeled probes generated by PCR targeting the open reading frame (ORF) to detect histones H2A, H2B, H3, H4, and H1 and used 7SK snRNA as a loading control (Fig. 2A). The abundance of histone H2A, H2B, H3, and H4 mRNAs is reduced to 37% to 70% of control levels in the SLBP knockdown cells when compared to the C2 control.

SIGNOR-265393

O43464

Q16611

0

relocalization

up-regulates

0.295

Bax and/or bak-mediated release of pro-apoptotic mediators including smac/diablo and omi

SIGNOR-118908

P40763

P06239

0

phosphorylation

up-regulates activity

0.699

Lck was able to induce tyrosine phosphorylation of STAT3 to a level equal to or greater than that induced by Jak2.|This finding, along with the previous data, gives strong evidence that Lck can directly and positively affect STAT3 activity.Our data provide strong evidence that Lck can activate STAT3 via phosphorylation in baculovirus infected insect cells.

SIGNOR-279201

P49137

Q7L5N7

1

phosphorylation

up-regulates activity

0.2

Mass spectrometry and mutagenesis analyses identified Ser34 of LPCAT2 as the phosphorylation site to enhance the catalytic activities. The experiments using inhibitors and siRNA against MAPK cascades demonstrated that LPCAT2 phosphorylation through LPS-TLR4 signaling may directly depend on MAPK-activated protein kinase 2 (MAPKAP kinase 2 or MK2).

SIGNOR-263077

O75874

A8MYZ6

0

transcriptional regulation

up-regulates quantity by expression

0.2

We identify FOXOs as transcriptional activators of IDH1. FOXOs promote IDH1 expression and thereby maintain the cytosolic levels of α-ketoglutarate and NADPH.

SIGNOR-260092

P19838

Q9Y297

0

polyubiquitination

down-regulates quantity by destabilization

0.589

Here we demonstrate that following IkappaB kinase (IkappaK)-mediated phosphorylation, the C-terminal domain of p105 (residues 918-934) serves as a recognition motif for the SCF(beta)(-TrCP) ubiquitin ligase.In vitro, SCF(beta)(-TrCP) specifically conjugates and promotes processing of phosphorylated p105.

SIGNOR-272570

Q86Y07

P29401

1

phosphorylation

up-regulates activity

0.2

Mechanistically, VRK2 promoted Thr287 phosphorylation of TKT and then recruited FBXL6 to promote TKT ubiquitination and activation.

SIGNOR-277842

P68400

Q8N5B7

1

phosphorylation

up-regulates activity

0.2

Most of the phosphorylated residues conformed to a consensus motif for phosphorylation by casein kinase 2 (CK2), and treatment of cells with the CK2-specific inhibitor CX-4945 lowered the phosphorylation levels of CERS2, -4, -5, and -6. Phosphorylation of CERS2 was especially important for its catalytic activity, acting mainly by increasing itsVmaxvalue.

SIGNOR-273987

P07550

P06213

0

phosphorylation

down-regulates activity

0.377

Insulin (10 nM)-stimulated rIR-catalyzed phosphorylation of β2-adrenergic receptor peptides was found prominently in peptides L339 (Tyr350 and Tyr354), T362 (Tyr364), and to a lesser extent peptides Y132 (Tyr132 and Tyr141), and I135 (Tyr141). G-protein-linked receptors and intrinsic tyrosine-kinase growth receptors represent two prominent modalities in cell signaling. Cross-regulation among members of both receptor superfamilies has been reported, including the counter-regulatory effects of insulin on β-adrenergic catecholamine action. Cells stimulated by insulin show loss of function and increased phosphotyrosine content of β2-adrenergic receptors.

SIGNOR-251302

P31749

Q15633

1

phosphorylation

up-regulates activity

0.2

We demonstrate that S6 kinases can phosphorylate the extended C-terminal domain of TRBP and interact with TRBP in situ in primary cells. TRBP serines 283/286 are essential for S6K-mediated TRBP phosphorylation, optimal expression of TRBP, and the S6K-TRBP interaction in human primary cells.

SIGNOR-274067

O15530

O43865

1

phosphorylation

down-regulates activity

0.2

Residue 68 resides in a consensus phosphorylation site for PKD (Figure 1A) [22,23]. Interestingly, phosphorylation of Ser68 could allow for subsequent phosphorylation of Ser71, Ser74, Ser77 and Ser80 by CK1, for which the consensus phosphorylation site is pS/T-X-X-S/T| We found that phosphorylation of Ser71 and Ser74 were sufficient to enable inhibition of IP3 binding to the IP3R

SIGNOR-249174

P84022

O15105

0

transcriptional regulation

down-regulates quantity

0.613

The downstream molecules including mad2, smad3, smad4 and smad7 are involved in TGF-β1-induced EMT,while Smad7 blocks the smad3 expression

SIGNOR-260437

P19838

P50591

0

post transcriptional regulation

up-regulates quantity by expression

0.302

Treatment with TRAIL increased the NF-κB transcriptional activity by approximately twofold in MDA-MB-231 cells compared to the control.

SIGNOR-277936

O43257

Q16539

0

phosphorylation

up-regulates

0.314

We show that the srcap subunit named znhit1 or p18(hamlet), which is a substrate of p38 mapk, is recruited to the myogenin promoter at the onset of muscle differentiation, in a p38 mapk-dependent manner. Furthermore, p18hamlet was phosphorylated during myoblast differentiation in a p38 mapk-dependent manner (dal testo pmc)

SIGNOR-165571

P17706

P29353

1

dephosphorylation

down-regulates activity

0.572

However, TC45 inhibited the EGF-induced association of p52Shc with Grb2, which was attributed to the ability of the PTP to recognize specifically p52Shc phosphorylated on Y239. These results indicate that TC45 recognizes not only selected substrates in a cellular context but also specific sites within substrates and thus may regulate discrete signaling events.

SIGNOR-248397

O95239

Q13131

0

phosphorylation

up-regulates activity

0.2

We found that the strong direct substrate KIF4A is phosphorylated by AMPK at Ser801.Using in vitro kinase assays, we found that active AMPK and Aurora B phosphorylated KIF4A at Ser801 and Thr799 respectively in a time-dependent manner (Figure 5D). KIF4A is phosphoregulated by AMPK and Aurora B. Although AMPK phosphorylation increased the ATPase activity of KIF4A, Aurora B phosphorylation resulted in a stronger increase (Figure 5I), which might be consistent with the more powerful kinase function of Aurora B during mitosis.

SIGNOR-265991

Q13322

P27361

0

phosphorylation

up-regulates

0.298

Phosphorylation of grb10 by mitogen-activated protein kinase: identification of ser150 and ser476 of human grb10zeta as major phosphorylation sitesreplacing ser(150) and ser(476) with alanines reduced the inhibitory effect of human grb10zeta on insulin-stimulated irs1 tyrosine phosphorylation

SIGNOR-138171

Q96S59

Q13315

0

phosphorylation

up-regulates activity

0.439

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

SIGNOR-279005

P67775

Q9UPZ9

1

dephosphorylation

down-regulates

0.2

In addition, mass spectrometry showed that pp2a treatment completely abolished the dually phosphorylated form, leaving only the singly phosphorylated form (data not shown). We conclude that a portion of ick in unstimulated and asynchronized hek293t cells is dually phosphorylated on the tdy motif.

SIGNOR-138432

P12931

P15514

1

cleavage

up-regulates

0.345

Ep2 can also promote the transactivation of epidermal growth factor receptor (egfr) expressed in colon cancer cells through src, which activates the proteolytic release of the egfr ligands amphiregulin (ar) and transforming growth factor-alfa (tgfalfa)125, thereby stimulating the egfr- network.

SIGNOR-236537

Q13464

P53671

1

phosphorylation

up-regulates

0.632

Specific activation of lim kinase 2 via phosphorylation of threonine 505 by rock, a rho-dependent protein kinase

SIGNOR-82755

P08237

Q8IYT8

0

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-274044

Q9H0M0

Q9Y2J4

1

ubiquitination

up-regulates activity

0.29

AMOTL2 mono-ubiquitination by WWP1 promotes contact inhibition by facilitating LATS activation|Here, we provide evidence that the E3 ligase WWP1 (WW-domain containing protein 1) mono-ubiquitinates AMOTL2 (angiomotin-like 2) at K347 and K408.

SIGNOR-271873

P60510

P06493

1

dephosphorylation

down-regulates activity

0.397

PP4c efficiently dephosphorylates Cdk1 sites of NDEL1 but does not dephosphorylate the Aurora A site.|We also found that PP4c negatively regulates Cdk1 activity in interphase.

SIGNOR-277162

Q7L0Q8

P12931

0

phosphorylation

down-regulates activity

0.534

Regulation of the Rho family small GTPase Wrch-1/RhoU by C-terminal tyrosine phosphorylation requires Src. Phosphorylation at Y254 negatively regulates Wrch-1-mediated biological functions.Serum-stimulated tyrosine phosphorylation and relocalization of Wrch-1 decreases its activation of downstream effectors in a Y254-dependent manner.

SIGNOR-259814

P07948

P11912

1

phosphorylation

up-regulates activity

0.738

Y182 of CD79a appears to be the initial and preferred site of Ag receptor phosphorylation by Src family kinases. In vitro, Src family Lyn and Fyn predominantly phosphorylate this residue in CD79a, and Y195 does so in CD79b. phosphorylation of Y182 alone can lead to further kinase activation and/or effector focusing necessary for phosphorylation of certain downstream targets, such as p62, p110, and Shc, but not others, such as Vav.

SIGNOR-251397

P17612

Q9GZU1

1

phosphorylation

down-regulates

0.2

The stimulatory effect of h89 on mcoln1 function was not observed when ser(557) and ser(559) were mutated to alanine residues, indicating that these two residues are essential for pka-mediated negative regulation of mcoln1.

SIGNOR-158946

O15111

Q9NQC7

1

phosphorylation

up-regulates activity

0.544

The phosphorylation of cyld was completely abolished by the combined mutations of the entire serine cluster (m4, lane 5). Similar results were obtained with the ikk holoenzyme (fig. 4c, panel 1), recombinant ikk_ (panel 2), and recombinant ikk_cyld phosphorylation may serve as a mechanism to inactivate its traf2 deubiquitination activity.

SIGNOR-204692

P30622

P68400

0

phosphorylation

up-regulates

0.293

Herein, we have identified polo-like kinase 1 (plk1) and casein kinase 2 (ck2) as two kinases of clip-170 and mapped s195 and s1318 as their respective phosphorylation sites.Plk1- and ck2-associated phosphorylations of clip-170 are involved in the timely formation of kinetochore-microtubule attachments in mitosis

SIGNOR-167168

O95863

Q15139

0

phosphorylation

down-regulates activity

0.466

Pkd1 phosphorylates ser(11) (s11) on transcription factor snail, a master emt regulator and repressor of e-cadherin expression, triggering nuclear export of snail via 14-3-3_ binding. Pkd1 regulates the expression of e-cadherin at the promoter level through direct phosphorylation of the transcriptional repressor snai1. Pkd1-mediated phosphorylation of snai1 occurs in the nucleus and generates a nuclear, inactive dna/snai1 complex that shows decreased interaction with its co-repressor ajuba.

SIGNOR-168537

Q9P0K8

Q9HC98

0

phosphorylation

up-regulates activity

0.2

Additionally, we found that NEK6 phosphorylated FOXJ2 at Thr23 and Ser254 ( xref , lanes 3 and 5), and NCOA5 at Ser21 and Ser151 ( xref , lanes 3 and 4).

SIGNOR-278965

Q76LX8

P04275

1

cleavage

down-regulates activity

0.599

Proteolytic degradation of VWF by ADAMTS-13 downregulates the proinflammatory potential of VWF.

SIGNOR-251966

P23443

O94763

1

phosphorylation

down-regulates activity

0.344

Here we report that the prefoldin chaperone URI represents a mitochondrial substrate of S6K1. In growth factor-deprived or rapamycin-treated cells, URI forms stable complexes with protein phosphatase (PP)1gamma at mitochondria, thereby inhibiting the activity of the bound enzyme. Growth factor stimulation induces disassembly of URI/PP1gamma complexes through S6K1-mediated phosphorylation of URI at serine 371.

SIGNOR-262943

P18846

P68400

0

phosphorylation

up-regulates

0.296

Camk ii phosphorylates only ser63 (corresponding to ser133 of creb), which is essential for the activation, and not ser72 (corresponding to ser142 of creb), which is a negative regulation site

SIGNOR-42565

P19525

P04637

1

phosphorylation

up-regulates

0.571

The double-stranded rna activated protein kinase pkr physically associates with the tumor suppressor p53 protein and phosphorylates human p53 on serine 392 in vitro.

SIGNOR-68033

P21731-2

P17252

0

phosphorylation

down-regulates activity

0.521

These data suggest a model whereby agonist-induced PKC phosphorylation of Ser(145) partially impairs TPbeta signalling while GRK2/3 phosphorylation at both Ser(239) and Ser(357) within its IC(3) and C-tail domains, respectively, sterically inhibits G-protein coupling, profoundly desensitizing signalling, and promotes beta-arrestin association and, in turn, facilitates TPbeta internalization.

SIGNOR-274092

P68400

P55010

1

phosphorylation

up-regulates

0.394

We find that eif5 is associated with ck2 when the kinase activity is at the highest level in vivo, and is phosphorylated at ser389 and ser390 by ck2.

SIGNOR-141159

Q12888

Q16539

0

phosphorylation

down-regulates activity

0.28

Here we show that 53BP1 is phosphorylated during mitosis on two residues, T1609 and S1618, located in its well-conserved ubiquitination-dependent recruitment (UDR) motif.|Dephosphorylation enables the recruitment of 53BP1 to double-strand DNA breaks |phosphorylation of T1609 is likely to be mediated by p38 MAPK

SIGNOR-264446

Q92570

P04637

0

transcriptional regulation

up-regulates quantity by expression

0.264

We showed that p53 directly bound the promoter of NR4A3 gene and induced its transcription. p53 transactivates the NR4A3 promoter in H1299 cells.

SIGNOR-256200

Q15759

Q06413

1

phosphorylation

up-regulates activity

0.538

In this study, we demonstrate that among the different Mitogen-activated protein kinases, the MADS-box transcription factors MEF2A and MEF2C are preferentially phosphorylated and activated by the p38 subfamily members p38alpha and p38beta2.

SIGNOR-280025

P31749

O75376

1

phosphorylation

down-regulates

0.424

Akt-induced phosphorylation of n-cor at serine 1450 contributes to its misfolded conformational dependent loss (mcdl) in acute myeloid leukemia of the m5 subtype.

SIGNOR-198913

P06493

P40337

1

phosphorylation

up-regulates activity

0.2

Mechanistically, CDK1 directly phosphorylates pVHL at Ser80, which primes the recognition of pVHL by PIN1.|PIN1 and CDK1 cooperatively modulate the protein turnover of pVHL, thereby conferring tumor growth, chemotherapeutic resistance and metastasis both in vitro and in vivo.

SIGNOR-280207

Q12913

P35968

1

dephosphorylation

down-regulates

0.699

The autoactivation residues y1054 and y1059 are targeted by dep-1 and this results in the inhibition of kinase activity and the consequent general dephosphorylation of vegfr2.

SIGNOR-181672

P03372

P04626

0

phosphorylation

up-regulates

0.572

The results presented here show for the first time that er redistribution to the cytoplasm and its interaction with her2 are important downstream effects of her2 overexpression, that erk1/2 is important for er cytoplasmic localization, and that subcellular localization of er may play a mechanistic role in determining the responsiveness of breast cancer cells to tamoxifen.

SIGNOR-124962

P35580

Q06413

0

transcriptional regulation

up-regulates quantity by expression

0.345

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-238769

P02671

P39900

0

cleavage

down-regulates quantity by destabilization

0.2

Matrix metalloproteinases collagenase-2, macrophage elastase, collagenase-3, and membrane type 1-matrix metalloproteinase impair clotting by degradation of fibrinogen and factor XII| We have now investigated the role of collagenase-2 (MMP-8), macrophage elastase (MMP-12), collagenase-3 (MMP-13), and membrane type 1-matrix metalloproteinase (MT1-MMP, MMP-14) in the degradation of fibrinogen and Factor XII of the plasma clotting system. |Fibrinogen was subjected to MMP-cleavage, and the resulting fragments were isolated. The amino acid sequences were determined by automated Edman degradation.|MMP-12 20ADSGEGD a-chain| 540FVSETESRG a-chain|433LVTSKGDK a-chain

SIGNOR-263622

Q13627

P46527

1

phosphorylation

up-regulates activity

0.332

DYRK1A phosphorylates p27 Kip1 at Ser10 in primary neurons and in vivo.|Thus, our results identify DYRK1A as the predominant kinase that phosphorylates and stabilizes p27Kip1 during neuronal differentiation.

SIGNOR-278250

O14733

O43318

0

phosphorylation

up-regulates activity

0.645

Upon TNFα stimulation, MEKK1, ASK1, and TAK1 phosphorylate and activate MKK7, which in turn activates JNK

SIGNOR-274146

Q16512

P36871

1

phosphorylation

up-regulates

0.2

Pak1-mediated phosphorylation of pgm selectively on threonine 466 significantly increased pgm enzymatic activity

SIGNOR-128722

P51817

O43541

1

phosphorylation

up-regulates activity

0.431

In vitro phosphorylation assays demonstrated that PrKX phosphorylates Smad6 at a serine residue.

SIGNOR-279270

O95278

Q9UQK1

1

dephosphorylation

up-regulates quantity by stabilization

0.749

We have recently described that the activity of R5/PTG is down-regulated by the laforin-malin complex, composed of a dual specificity phosphatase (laforin) and an E3-ubiquitin ligase (malin). We now demonstrate that phosphorylation of R5/PTG at Ser-8 by AMPK accelerates its laforin/malin-dependent ubiquitination and subsequent proteasomal degradation, which results in a decrease of its glycogenic activity.

SIGNOR-276239

O14786

Q04741

0

transcriptional regulation

up-regulates quantity by expression

0.2

EMX1 activates the transcription of Nrp1 in vitro.

SIGNOR-261593

P43405

P29353

1

phosphorylation

up-regulates

0.762

The syk-family kinases (syk and zap-70) were able to phosphorylate the y239 and y240 sites, and less efficiently the y317 site on sch1 (iso2).

SIGNOR-59635

P45983

Q14934

1

phosphorylation

up-regulates activity

0.467

Here, we showed that the nuclear factor of activated T3 (NFAT3) is phosphorylated by JNK1 or JNK2 at Ser(213) and Ser(217), which are located in the conserved SP motif.|Moreover, a 3xNFAT-luc reporter gene assay indicated that NFAT3 transcriptional activity was increased in a dose dependent manner by JNK1 or JNK2.

SIGNOR-280033

P61586

Q14192

1

relocalization

up-regulates

0.348

Here, we show that stimulation of the rho pathway induces translocation of the transcriptional lim-only coactivator fhl2 to the nucleus and subsequent activation of fhl2- and androgen receptor-dependent genes.

SIGNOR-114071

Q9NRC8

P84243

1

deacetylation

up-regulates activity

0.2

SIRT7 links H3K18 deacetylation to maintenance of oncogenic transformation.|Genome-wide binding studies reveal that SIRT7 binds to promoters of a specific set of gene targets, where it deacetylates H3K18Ac and promotes transcriptional repression.

SIGNOR-275872

Q13480

P08581

0

phosphorylation

up-regulates activity

0.674

Gab-1 is phosphorylated on the same residues by HGF and EGF receptors. Among 16 peptides only nine were phosphorylated by the EGF and HGF receptors, namely peptides containing the tyrosine residues 285, 307, 373, 407, 448, 473, 590, 628 and 660. we show that in the response to HGF or EGF, Gab1 is phosphorylated in vivo on the same residues. However, a sustained activation of signaling pathways downstream to Gab1 (as a result of its sustained phosphorylation) is achieved only in response to HGF.

SIGNOR-250290

P16220

P51812

0

phosphorylation

up-regulates activity

0.726

MAPK activates CREB kinase, which in turn phosphorylates and activates CREB. Purification, sequencing, and biochemical characterization of CREB kinase revealed that it is identical to a member of the pp90(RSK) family, RSK2. RSK2 was shown to mediate growth factor induction of CREB serine-133 phosphorylation both in vitro and in vivo. These findings identify a cellular function for RSK2 and define a mechanism whereby growth factor signals mediated by RAS and MAPK are transmitted to the nucleus to activate gene expression

SIGNOR-248951

P27361

Q9HBH9

1

phosphorylation

up-regulates

0.517

Erk and p38 phosphorylate mnk1 and mnk2, which stimulates their in vitro kinase activity.

SIGNOR-48355

Q92630

Q13315

0

phosphorylation

up-regulates quantity by stabilization

0.558

ATM augments nuclear stabilization of DYRK2 by inhibiting MDM2 in the apoptotic response to DNA damage|Upon exposure to genotoxic stress, ATM phosphorylates DYRK2 at Thr-33 and Ser-369, which enables DYRK2 to escape from degradation by dissociation from MDM2 and to induce the kinase activity toward p53 at Ser-46 in the nucleus.

SIGNOR-275577

P63000

O75962

0

guanine nucleotide exchange factor

up-regulates activity

0.692

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-260579

Q5VT25

P10916

1

phosphorylation

up-regulates activity

0.65

These approximately 190-kDa myotonic dystrophy kinase-related Cdc42-binding kinases (MRCKs) preferentially phosphorylate nonmuscle myosin light chain at serine 19, which is known to be crucial for activating actin-myosin contractility.

SIGNOR-250723

P06493

Q99459

1

phosphorylation

up-regulates activity

0.624

Cdc5-dependent Net1 phosphorylation and Cdc14 release from the nucleolus require prior Cdc5 activation by Cdk1 and active separase to promote Cdc14 activation.|Cdk1 initially phosphorylates Cdc5, mostly at T242 and T238 (T242 phosphorylation is especially relevant based on our results), and phosphorylation activates its kinase activity, which is essential for anaphase progression.

SIGNOR-279597

Q16625

Q02156

0

phosphorylation

up-regulates

0.2

Thr403, thr404, thr424 and thr438 in the occludin c-terminal domain are the predominant sites of pkc_-dependent phosphorylation . The present study demonstrates that pkc_ phosphorylates occludin on specific threonine residues and promotes assembly of epithelial tight junctions.

SIGNOR-173643

P35637

P78352

1

post transcriptional regulation

up-regulates quantity

0.27

These results point toward a novel mechanism by which FUS targets neuronal mRNA and given that these PSD-95 and Shank1 3'-UTR G quadruplex structures are also targeted by the fragile X mental retardation protein (FMRP), they raise the possibility that FUS and FMRP might work together to regulate the translation of these neuronal mRNA targets.|As seen in Figure 7 (top panel), both PSD-95 Q1-Q2 and Shank1a GQ probes pulled down endogenous FUS, whereas their M2 mutants did not, indicating that the GQ structure is sufficient for recognition.

SIGNOR-262103

P68400

P0DP23

1

phosphorylation

down-regulates activity

0.422

Phosphorylation of CaM at four sites by CK2 was found to follow a sequential order, with Ser81 as the first, Thr79 as the second, and Ser101 or Thr117 as the third.

SIGNOR-266355

Q92626

P53420

1

catalytic activity

up-regulates quantity by stabilization

0.256

Peroxidasin (PXDN), an ECM protein with peroxidase activity, is integral to basement membrane consolidation through catalysis of sulfilimine bonds in collagen IV. PXDN has been shown to form dityrosine crosslinks and also catalyses sulfilimine bonds, in the presence of hypohalous acids, to connect collagen IV protomers, which are an integral component of the basement membrane

SIGNOR-265250

Q9Y4P1

Q99942

0

ubiquitination

down-regulates quantity by destabilization

0.405

These results substantiate the notion that RNF5 negatively regulates ATG4B availability with concomitant effect on LC3 processing and autophagy under normal growth conditions.|These results suggest that RNF5 directly induces ATG4B ubiquitination.

SIGNOR-278664

Q9UHD2

P35813

0

dephosphorylation

down-regulates activity

0.41

Furthermore, PPM1A, but not PPM1B, serves as an efficient phosphatase to dephosphorylate Ser 172 residue of both TBK1 and IKKepsilon kinases, which is critical for their kinase activities.|In a similar in vitro phosphatase assay, incubation of PPM1A also eliminated TBK1 and IKKepsilon phosphorylation at Ser 172 residue, evidenced by phospho-S172 immunoblotting (XREF_FIG, F and G).|These observations suggest that PPM1A may block kinase activities of TBK1 and IKKepsilon.

SIGNOR-276966

P08254

Q99075

1

cleavage

up-regulates

0.517

It was concluded that mmp-3 cleaves hb-egf at a specific site in the jm domain and that this enzyme might regulate the conversion of hb-egf from being a juxtacrine to a paracrine/autocrine growth factor.

SIGNOR-83339

Q8WU20

P22681

0

ubiquitination

down-regulates

0.576

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

SIGNOR-87166

P46527

Q00535

0

phosphorylation

down-regulates activity

0.643

CDK5 knockdown in HEY cells significantly prolonged the half-life of TP53 and p27 Kip1 proteins (XREF_FIG).|During neural stem cell differentiation, CDK5 can phosphorylate p27 at Thr187 and at Ser10, promoting neurite outgrowth as neurons differentiate .

SIGNOR-279681

O14746

P06493

0

phosphorylation

up-regulates activity

0.324

Here we report that hTERT is phosphorylated at threonine 249 during mitosis by the serine/threonine kinase CDK1.These observations indicate that phosphorylation at threonine 249 regulates hTERT RdRP and contributes to cancer progression in a telomere independent manner.

SIGNOR-277517

Q15717

O14672

1

post transcriptional regulation

up-regulates quantity

0.2

Neuronal ELAV (nELAV) proteins are RNA-binding proteins which play a physiological role in controlling gene expression in memory formation, and their alteration may contribute to cognitive impairment associated with neurodegenerative pathologies such as Alzheimer's disease (AD). The experiments show for the first time that ADAM10mRNA represents a nELAV target and that these RNA-binding proteins can play a role in the post-transcriptional regulation of ADAM10 expression. nELAV proteins specifically bind the ADAM10 mRNA and this binding is disrupted following Aβ exposure

SIGNOR-266862

P17252

P28329

1

phosphorylation

up-regulates

0.383

We show that chat is differentially phosphorylated by protein kinase c (pkc) isoforms on four serines (ser-440, ser-346, ser-347, and ser-476) and one threonine (thr-255). This phosphorylation is hierarchical, with phosphorylation at ser-476 required for phosphorylation at other serines. Phosphorylation at some, but not all, sites regulates basal catalysis and activation.

SIGNOR-129264

P36508

P17987

1

transcriptional regulation

up-regulates quantity by expression

0.347

The transcription from the minimalCcta promoter was up-regulated 3-fold by ZNF143 and 6-fold by ZNF76 when full-length proteins were co-expressed, indicating that both ZNF143 and ZNF76 can enhance Ccta transcription.

SIGNOR-266221

Q14114

P06241

0

phosphorylation

up-regulates quantity

0.635

Fyn phosphorylates ApoER2.|Together these data demonstrate that Fyn activity is necessary for its effects increasing ApoER2 levels.

SIGNOR-278197

P49841

O95863

1

phosphorylation

down-regulates

0.557

Snail is a well-known zn-finger transcription factor that promotes emt by repressing e-cadherin expression. It is known that snail is phosphorylated by gsk3beta and degraded by beta-trcp-mediated ubiquitination. A variant of snail (snail-6sa), which abolishes these phosphorylations, is much more stable and resides exclusively in the nucleus to induce emt

SIGNOR-129402

P63279

P59595

1

sumoylation

up-regulates activity

0.2

In this study, we identified Ubc9 as a host protein that interacts specifically with SARS-CoV N protein. This interaction was verified both in vivo and in vitro. Furthermore, we showed that, in addition to phosphorylation, the N protein was modified by covalent attachment of SUMO to its lysine 62 residue. Evidence provided demonstrated that sumoylation may promote homo-oligomerization of the protein.

SIGNOR-260263

Q9Y2X7

P12931

0

phosphorylation

up-regulates activity

0.542

Tyrosines 246 and 293 are required to hold GIT1 in a closed conformation.Hyperphosphorylation of GIT1-N by Src and pervanadate does not affect its binding in vitro to full length GIT1 proteins. Mutations Y246E and Y293E of GIT1 enhance binding to paxillin.

SIGNOR-276627

O14757

P84243

1

phosphorylation

down-regulates activity

0.2

We identify chk1 as the kinase responsible for h3-t11 phosphorylation. H3-t11 phosphorylation occurs throughout the cell cycle and is chk1 dependent in vivo.Phosphorylation at thr-12 (h3t11ph) by pkn1 is a specific tag for epigenetic transcriptional activation that promotes demethylation of lys-10 (h3k9me) by kdm4c/jmjd2c.

SIGNOR-160557

P50542

Q13315

0

phosphorylation

up-regulates activity

0.497

Specificity for autophagy of peroxisomes (pexophagy) is provided by ATM phosphorylation of PEX5 at Ser 141, which promotes PEX5 monoubiquitylation at Lys 209, and recognition of ubiquitylated PEX5 by the autophagy adaptor protein p62, directing the autophagosome to peroxisomes to induce pexophagy.

SIGNOR-262792

Q9UBN7

P00533

0

phosphorylation

down-regulates

0.44

A negative feedback loop consisting of egfr-mediated phosphorylation of hdac6 tyr(570) resulted in reduced deacetylase activity and increased acetylation of alpha-tubulin.

SIGNOR-162431

P35222

Q9P289

0

phosphorylation

up-regulates quantity by stabilization

0.2

In response to Wnt3a stimulation, the kinase MST4 directly phosphorylates \u03b2-catenin at Thr40 to block its Ser33 phosphorylation by GSK3\u03b2.

SIGNOR-280141

P25445

Q9NP71

0

transcriptional regulation

up-regulates quantity by expression

0.2

The present study provides evidence for a direct and dominant role of ChREBP in the glucose regulation of two key liver lipogenic enzymes, acetyl-CoA carboxylase (ACC) and fatty acid synthase (FAS)

SIGNOR-267947

O15524

O60674

1

ubiquitination

down-regulates quantity by destabilization

0.795

Shp-2 regulates socs-1-mediated janus kinase-2 ubiquitination/degradation downstream of the prolactin receptor

SIGNOR-118407

P68431

Q7LBC6

0

demethylation

down-regulates activity

0.2

We have purified a JmjC domain-containing protein, JHDM2A, which specifically demethylates mono- and dimethyl-H3K9. JHDM2A exhibits hormone-dependent recruitment to androgen-receptor target genes, resulting in H3K9 demethylation and transcriptional activation. Thus, our work identifies a histone demethylase and links its function to hormone-dependent transcriptional activation.

SIGNOR-266634

P49841

Q99250

1

phosphorylation

down-regulates activity

0.2

Glycogen synthase kinase 3β (GSK3beta) phosphorylates the Nav1.2C-terminal tail at T1966, suppressing Na+ currents and channel trafficking to the plasma membrane

SIGNOR-275748

O15033

O43236

1

ubiquitination

down-regulates quantity by destabilization

0.2

Furthermore, the ubiquitination and degradation of SMAC, HtrA2, and ARTS were significantly enhanced in AREL1-expressing cells following apoptotic stimulation, indicating that AREL1 binds to and ubiquitinates cytosolic but not mitochondria-associated forms of IAP antagonists

SIGNOR-267670

P61586

O60890

0

gtpase-activating protein

up-regulates activity

0.636

OPHN-1 colocalized with the actin cytoskeleton in neuronal and glial cells. We have previously shown that OPHN1 stimulates GTPases activity of RhoA, Cdc42, and Rac1 in vitro

SIGNOR-268397

P60953

A1L390

0

guanine nucleotide exchange factor

up-regulates activity

0.354

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-260585

P46937

P48730

0

phosphorylation

down-regulates

0.421

LATS1/2-mediated phosphorylation of a conserved serine in this region (Ser311 in human TAZ; Ser397 in human YAP) primes for further phosphorylation by CK1_/_ kinases (Ser314 on human TAZ; Ser400/403 in human YAP)

SIGNOR-230738

P68400

O95863

1

phosphorylation

up-regulates quantity by stabilization

0.348

Serines 11 and 92 participate in the control of snail1 stability and positively regulate snail1 repressive function and its interaction with msin3a corepressor. Furthermore, serines 11 and 92 are required for snail1-mediated emt and cell viability, respectively. Pka and ck2 have been characterized as the main kinases responsible for in vitro snail1 phosphorylation at serine 11 and 92, respectively.

SIGNOR-161771

Q8IVP5

P68400

0

phosphorylation

down-regulates activity

0.427

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

SIGNOR-273622

Q9NP58

Q16236

0

transcriptional regulation

up-regulates quantity by expression

0.2

NFE2L2 is stabilized and translocates to the nucleus, where it dimerizes with sMAF proteins. This complex binds to AREs to mediate the transcription of genes involved in iron metabolism, GSH metabolism, and ROS detoxification.Two critical enzymes in this pathway, ATP binding cassette subfamily B member 6 (ABCB6) and ferrochelatase (FECH), are regulated by the transcription factor NFE2L2 and play significant roles in inhibiting ferroptosis when upregulated.

SIGNOR-279864

P67775

P19429

1

dephosphorylation

down-regulates

0.401

The major phosphatase thought to dephosphorylate ctni and phospholamban is type 2a protein phosphatase (pp2a) [61]. Activation of pp2a and ensuing dephosphorylation of regulatory proteins is involved in the anti-adrenergic effects of adenosine and muscarinic receptor activation see also fig2.

SIGNOR-134601

Q16584

P45985

1

phosphorylation

up-regulates

0.625

These data suggest that mlk-3 phosphorylates sek1 directly and that it does so specifically on those residues known to activate sek1 in vivo.

SIGNOR-75836

P53355

O95786

1

phosphorylation

down-regulates activity

0.33

DAPK1 also phosphorylates the N-terminal serine at position 8 (S8) of RIG-I, which is also reported to undergo phosphorylation by PKC-\u03b1/\u03b2 to suppress TRIM25-mediated RIG-I ubiquitination, thereby negatively regulating RIG-I activity (84).

SIGNOR-279519

O15273

Q9UKT6

0

ubiquitination

down-regulates quantity by destabilization

0.2

FBXL21 is a clock-controlled E3 ligase modulating circadian periodicity via subcellular-specific CRYPTOCHROME degradation. How FBXL21 regulates tissue-specific circadian physiology and what mechanism operates upstream is poorly understood. Here we report the sarcomere component TCAP as a cytoplasmic substrate of FBXL21.

SIGNOR-264853