GleghornLab/Signor_processed · Datasets at Hugging Face

IdA stringlengths 6 21	IdB stringlengths 6 21	mechanism stringclasses 40 values	effect stringclasses 10 values	score float64 0.1 0.99 ⌀	sentence stringlengths 10 1.63k ⌀	signor_id stringlengths 12 14
P08237	O60502	deglycosylation	up-regulates activity	0.2	Our previous investigation on O-GlcNAcylation of PFK1 has demonstrated that O-GlcNAcylation inhibits PFK1 enzyme activity\|In cells, a single set of antagonistic enzymes-O-GlcNAc transferase (OGT) and O-GlcNAc hydrolase are responsible for the addition and removal of GlcNAc moiety, respectively.	SIGNOR-267607
O60260	P62987	binding	up-regulates activity	0.2	The phosphorylation-dependent interaction between ubiquitin and parkin suggests that phosphorylated ubiquitin unlocks autoinhibition of the catalytic cysteine. Our results show that PINK1-dependent phosphorylation of both parkin and ubiquitin is sufficient for full activation of parkin E3 activity. These findings demonstrate that phosphorylated ubiquitin is a parkin activator.	SIGNOR-270344
Q4ZG55	Q14686	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
Q9NPD5	P53567	transcriptional regulation	up-regulates quantity by expression	0.2	Taken together, these findings suggest that the LPS-induced down-regulation of Oatp4 is likely due to reduction in the binding of HNF1alpha, C/EBP, HNF3, and RXR:RAR to the Oatp4 promoter.	SIGNOR-268986
Q9UKV5	Q92890	binding	up-regulates activity	0.2	Here we show that Ufd1 directly interacts with gp78 and functions as a cofactor. Ufd1 enhances the E3 activity of gp78, accelerates the ubiquitination and degradation of reductase, and eventually promotes receptor-mediated uptake of low-density lipoprotein.	SIGNOR-252425
Q99828	Q9UNE7	ubiquitination	down-regulates quantity	0.2	All those were suggesting that CHIP promotes CIB1 ubiquitination via the Lys 48 residue of ubiquitin.\|K10 and K65 were the Lysine (K) residues for CHIP mediated CIB1 degradation.	SIGNOR-278721
P42263	Q9BYB0	binding	up-regulates quantity	0.2	SHANK proteins are ‘master’ scaffolding proteins that tether and organize intermediate scaffolding proteins. They are located at excitatory synapses, where they are crucial for proper synaptic development and function. SAPAP proteins subsequently bind to the PDZ domain of members of the SHANK protein family. SHANK proteins then bind to the actin cytoskeleton and to Homer protein, which in turn interacts with mGluRs. Through these extended links, PSD95, SAPAP, SHANK and Homer proteins form a quaternary complex that brings together mGluR and NMDAR complexes in the PSD (FIG. 3).	SIGNOR-264603
O75385	P14373	ubiquitination	down-regulates quantity	0.2	STK38L ubiquitination promotes its activation and phosphorylation of ULK1 at Ser495, rendering ULK1 in a permissive state for TRIM27-mediated hyper-ubiquitination	SIGNOR-270349
Q9BZI1	P27361	phosphorylation	up-regulates activity	0.2	To identify the phosphorylated residue, we introduced a serine-to-alanine substitution at residues 294 and 326 and a threonine-to-alanine substitution at residue 331 in Irx2(291–356). Erk1 phosphorylated S294A and T331A, but not S326A (Fig. 4b), indicating that Ser326 is the bona fide MAP kinase target.	SIGNOR-263061
Q9NPD5	P42229	transcriptional regulation	up-regulates quantity by expression	0.2	PRL enhanced the binding of Stat5a to the OATP1B3 promoter and DNA-protein binding was inhibited in competition assays by excess OATP1B3 and Stat5 consensus oligomers but not by mutant Stat5 oligomers.\|PRL and GH induction of Oatp1b2 and OATP1B3 promoter activity required cotransfection of Stat5a and PRLRL or GHR.	SIGNOR-268990
Q86YD1	Q96BR1	phosphorylation	down-regulates quantity by destabilization	0.2	In this study, we find that the understudied serum and glucocorticoid-induced kinase-2 (SGK2) phosphorylates PTOV1 at S36.	SIGNOR-279283
E9PAV3	P49841	phosphorylation	down-regulates	0.2	Gsk3 beta-dependent phosphorylation of the alpha nac coactivator regulates its nuclear translocation and proteasome-mediated degradation.	SIGNOR-123262
Q8IYW5	P0C0S8	binding	up-regulates	0.2	Rnf168 is recruited to sites of dna damage by binding to ubiquitylated histone h2a.	SIGNOR-183890
Q01105	Q9UBY8	binding	down-regulates activity	0.2	CLN8 interacts with ceramide binding proteins PP2A and I2PP2A. We showed that the phosphorylation levels of several substrates of PP2A, namely Akt, S6 kinase, and GSK3β, were decreased in CLN8 disease patient fibroblasts. This reduction can be reversed by inhibiting PP2A phosphatase activity with cantharidin, suggesting a higher PP2A activity in CLN8-deficient cells. The phosphorylation levels of PP2A substrates are decreased in the absence of CLN8.	SIGNOR-265584
Q16695	Q9Y4C1	demethylation	up-regulates activity	0.2	Using a biochemical assay coupled with chromatography, we have purified a JmjC domain-containing protein, JHDM2A, which specifically demethylates mono- and dimethyl-H3K9.	SIGNOR-276846
Q16611	P54829	dephosphorylation	up-regulates activity	0.2	In this study, we report that on apoptotic stimulation Bak undergoes dephosphorylation at tyrosine residue 108 (Y108), a critical event that is necessary but not sufficient for Bak activation, but is required both for early exposure of the occluded N-terminal domain and multimerisation.	SIGNOR-248542
Q9NRM7	P17612	phosphorylation	up-regulates	0.2	Here, we show that cyclic amp (camp)-dependent protein kinase (pka) phosphorylates lats and thereby enhances its activity sufficiently to phosphorylate yap on ser381.	SIGNOR-236994
O00560	P59637	relocalization	up-regulates activity	0.2	Overall, these results support the hypothesis that the interaction of E protein PBM with syntenin facilitates the recruitment of syntenin in the cytosol and leads to p38 MAPK activation.	SIGNOR-260752
O14558	P17612	phosphorylation	down-regulates	0.2	Hosphorylation of hsp20 at ser16 is not only associated with cyclic nucleotide-dependent vasorelaxation but also inhibits agonist-induced contractile responses.	SIGNOR-66493
Q8TDY4	P00533	phosphorylation	up-regulates activity	0.2	How ACAP4 regulates membrane dynamics and curvature in response to EGF stimulation is unknown. Here, we show that phosphorylation of the N-terminal region of ACAP4, named the Bin, Amphiphysin, and RSV161/167 (BAR) domain, at Tyr34 is necessary for EGF-elicited membrane remodeling. \|EGF stimulation of cells causes phosphorylation of ACAP4 at Tyr34, which subsequently promotes ACAP4 homodimer curvature.	SIGNOR-272234
Q9UQ26	O95153	binding	down-regulates activity	0.2	SH3 domains of RBPs interact with RIMs. The enhancement of depolarization-induced secretion in PC12 cells by fusion proteins that suppress the associations of RBPs with RIMs and α1 suggests that RBPs may repress RIMs, either directly or through associated proteins.	SIGNOR-264368
O14950	Q12852	phosphorylation	up-regulates	0.2	Zip kinase (hzipk) phosphorylated the regulatory light chain of myosin ii (mrlc) at both ser19 and thr18 in vitro. In this study, we demonstrate that hzipk also induces the diphosphorylation of mrlc in nonmuscle cells.	SIGNOR-113664
P31751	P24666	dephosphorylation	down-regulates activity	0.2	Reduction in the levels of both LMW-PTP isoforms in vitro and in vivo increased tyrosine phosphorylation of IR and AktSer473 and increased IRS-1- and IRS-2-associated PI3-K activities in both liver and fat.\|Activated PI3-K stimulates Akt (or protein kinase B) that in turn phosphorylates and inactivates glycogen synthase kinase-3	SIGNOR-248456
P69905	P17509	transcriptional regulation	down-regulates quantity by repression	0.2	HOXB6 protein represses globin transcript levels in stably transfected K562 cells in a DNA-binding dependent fashion.	SIGNOR-261637
Q9NQA5	P17252	phosphorylation	up-regulates activity	0.2	A cell permeable analog of DAG increased TRPV5 activity within 30 min via protein kinase C activation of the channel since mutation of TRPV5 at the putative PKC phosphorylation sites S299 and S654 prevented the stimulatory effect of TK.	SIGNOR-149948
Q8TB45	P43405	phosphorylation	down-regulates activity	0.2	We found that tyrosine (Tyr) 289 phosphorylation of DEPTOR impairs its interaction with mTOR, leading to increased mTOR activation. Using proximity biotinylation assays, we identified SYK (spleen tyrosine kinase) as a kinase involved in DEPTOR Tyr 289 phosphorylation in an ephrin (erythropoietin-producing hepatocellular carcinoma) receptor-dependent manner.	SIGNOR-277572
P11908	Q13131	phosphorylation	down-regulates activity	0.2	We demonstrate here that glucose deprivation or hypoxia results in the AMPK-mediated phosphorylation of phosphoribosyl pyrophosphate synthetase 1 (PRPS1) S180 and PRPS2 S183, leading to conversion of PRPS hexamers to monomers and thereby inhibiting PRPS1/2 activity, nucleotide synthesis, and nicotinamide adenine dinucleotide (NAD) production.	SIGNOR-265731
Q9NYY3	Q9P253	ubiquitination	down-regulates quantity by destabilization	0.2	VPS18 Ubiquitylates SNK in Vitro and in Vivo. The ubiquitylation of proteins by hVPS18 was selectively mediated by UbcH4.	SIGNOR-271550
P11413	Q05655	phosphorylation	up-regulates	0.2	A pkc activator, significantly increased g6pd phosphorylation and activity, whereas single (s210a, t266a) and double (s210a/t266a) mutations at sites flanking the g6pd active site significantly inhibited phosphorylation, shifted the isoelectric point, and reduced enzyme activity.	SIGNOR-167053
Q99523	Q13177	phosphorylation	down-regulates activity	0.2	PAKs specifically phosphorylate Ser15 of the sortilin-cd and alter its trafficking. It can be concluded that PAK1-3 may indeed instigate the phosphorylation of sortilin and that they target a single serine residue (Ser15) located in the kinase domain-binding site of the sortilin-cd. Full-length sortilins with the serine at position 793 (residue 15 in the cytoplasmic domain) (for the sequence, see Fig. 2). Phosphorylation (Ser15) downregulates the sortilin–AP-1 interaction.	SIGNOR-273717
Q9H2X6	P54646	phosphorylation	down-regulates activity	0.2	AMPKalpha2-mediated inhibition of WIP1 phosphorylation by HIPK2\|Site-directed mutagenesis of Thr112 and Ser114 in the N terminus, and Thr1107 in the C terminus markedly reduced HIPK2 phosphorylation by AMPKalpha2 in vitro	SIGNOR-275485
Q32MZ4	P43405	phosphorylation	up-regulates activity	0.2	However, this inhibitory activity TRIP can be reversed by the co-expression of Syk, which might inhibit the activity of cytoplasmic TRIP, sequester TRIP from important nucleolar targets or even counter TRIP 's inhibitory effects on TRAF and TNF signaling by regulating the activity of alternative components of the pathway.\|Syk induces phosphorylation of TRIP on tyrosine.	SIGNOR-279297
Q15375	P56915	transcriptional regulation	down-regulates quantity by repression	0.2	We demonstrate that Goosecoid can act as a repressor of its own promoter activity in transient co-transfection experiments in mouse P19 cells and in Xenopus embryos. Autorepression depends on the presence of the homeodomain and is mediated through the prd element more proximal to the transcriptional start site.	SIGNOR-261613
P04234	O60858	polyubiquitination	down-regulates quantity by destabilization	0.2	RFP2, a gene frequently lost in various malignancies, encodes a protein with RING finger, B-box, and coiled-coil domains that belongs to the RBCC/TRIM family of proteins.Rfp2 Regulates the Stability of the ERAD Substrate CD3-δ. In summary, these experiments demonstrate that Rfp2 functions as a RING-dependent ERAD E3 ubiquitin ligase and regulates the degradation of the ER substrate, CD3-δ.	SIGNOR-271644
P48050	P17252	phosphorylation	down-regulates activity	0.2	These results therefore indicate that Kir2.3 is directly modulated by PKC phosphorylation of its channel protein and threonine 53 is the PKC phosphorylation site in Kir2.3.	SIGNOR-275965
P10412	Q96GD4	phosphorylation	up-regulates quantity by stabilization	0.2	we showed previously that phosphorylation of S27 in human histone H1.4 (H1.4S27-P), prevents binding of heterochromatin protein 1 (HP1) family members (officially known as chromobox protein homologs) to the neighboring dimethylated K26. Here, we present the first functional characterization of H1.4S27-P in vivo and in vitro. We show that H1.4S27 phosphorylation is cell-cycle-regulated and its levels peak on metaphase chromosomes. We identify further Aurora B as the kinase phosphorylating H1.4S27.	SIGNOR-262658
P07195	Q9NXA8	deacetylation	up-regulates activity	0.2	In colorectal cancer, SIRT5 binds to lactate dehydrogenase B (LDHB) to deacetylate it at Lysine 329, thereby increasing its enzymatic activity.	SIGNOR-267645
P04406	Q5XX13	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
O75962	Q00535	phosphorylation	up-regulates activity	0.2	Roscovitine inhibits the ability of Trio to activate Rac, and peptides corresponding to the Cdk5 consensus sites in Trio are phosphorylated by Cdk5.\|Together, these data suggest that control of the cortical actin cytoskeleton, long known to modulate hormone exocytosis and subsequent endocytosis, involves Cdk5 mediated activation of Trio.	SIGNOR-280220
P47989	Q00535	phosphorylation	up-regulates activity	0.2	Finally, threonine 222 of XOR is the critical target site for CDK5 dependent activation of XOR.\|Once we determined CDK5 was necessary for hypoxia induced hyperactivation of XOR, we tested whether CDK5 was sufficient to phosphorylate XOR and induce increased enzymatic activity in a cell free system.	SIGNOR-280221
Q9HAU4	Q13315	phosphorylation	up-regulates activity	0.2	Using biochemical approaches and MS analysis, we show that upon the onset of the DNA-damage response, SMURF2 becomes phosphorylated at Ser384 by ataxia telangiectasia mutated (ATM) serine/threonine kinase, and this phosphorylation is required for its interaction with RNF20.	SIGNOR-277534
P11908	Q9UHD2	phosphorylation	up-regulates activity	0.2	Here, we show that ionizing radiation results in TBK1-mediated phosphorylation of phosphoribosyl pyrophosphate synthetase (PRPS)1/2 at T228, thereby enhancing PRPS1/2 catalytic activity and promoting deoxyribonucleotide synthesis.	SIGNOR-277317
P68431	O15054	demethylation	down-regulates activity	0.2	Ubiquitously Transcribed Tetratricopeptide Repeat on chromosome X (UTX) and Jumonji D3 (JMJD3) as novel histone demethylases that catalyze the removal of di- and trimethyl groups on histone H3 lysine 27, thereby promoting target gene activation.	SIGNOR-260018
P11308	P48730	phosphorylation	down-regulates activity	0.2	Interestingly, only CKId, but not other CKI isoforms or CKII could promote ERG degradation under ectopic expression conditions (XREF_FIG).\|These results indicate that phosphorylation of ERG by CKIdelta within the SPOP-recognition degron triggers its interaction with SPOP to promote ERG destruction .	SIGNOR-280234
P09471	P47900	binding	up-regulates activity	0.2	Here we systematically quantified ligand-induced interactions between 148 GPCRs and all 11 unique G alpha subunit C-termini. For each receptor, we probed chimeric G alpha subunit activation via a transforming growth factor-alpha (TGF alpha) shedding response in HEK293 cells lacking endogenous Gq/11- and G12/13- signaling. \| We defined positive coupling if any member of the subfamily scored LogRAi ≥ -1 and negative coupling if all of the members scored LogRAi < -1 (Figure 3A-B). ROC analysis gives AUC = 0.78 (Figure S4A) when considering high-confidence known coupling data and suggested a threshold of LogRAi ≥ -1.0 for defining true couplings. \| The score associated to this interaction has a LogRAi ≥ -1.0.	SIGNOR-257185
Q9BXF6	Q15208	phosphorylation	up-regulates activity	0.2	We identified 5 potential NDR1 substrates in the mouse brain and chose two for functional validation. We show that one NDR1 substrate is another kinase, AP-2 associated kinase-1 (AAK1) which regulates dendritic branching as a result of NDR1 phosphorylation. Another substrate is the Rab8 guanine nucleotide exchange factor (GEF) Rabin8 (a Sec2p homolog) which we find is involved in spine synapse formation.	SIGNOR-263035
Q9Y458	P14921	transcriptional regulation	up-regulates quantity by expression	0.2	TBX22 is an X-linked gene, which encodes a T-box-containing transcription factor. Loss-of-function mutation in the X-linked TBX22 promoter disrupts an ETS-1 binding site and leads to cleft palate. We first link the transcription factor ETS-1 to TBX22 pathway during embryonic palatogenesis.	SIGNOR-265565
P53350	Q9BTA9	binding	up-regulates activity	0.2	Here, we report that the activation of Plk1 requires WAC, a WW domain-containing adaptor protein with a coiled-coil region that predominantly localizes to the nucleus in interphase. Cyclin-dependent kinase 1 (Cdk1) phosphorylates WAC, priming its direct interaction with the polo-box domain of Plk1.	SIGNOR-265036
P07948	Q9HCP0	phosphorylation	up-regulates quantity by stabilization	0.2	Although there have been more than 40 reports of mass spectrometric studies on phosphorylation at Lyn-S13, the kinase responsible remained unclear. We succeeded in identifying casein kinase 1γ (CK1γ) as the kinase responsible for phosphorylation of Lyn-S13. In HEK293 cells co-expressing Lyn and CK1γ, the phosphorylation level of Lyn-S13 increased significantly. we concluded that S-palmitoylated CK1γ encounters N-myristoylated Lyn and specifically phosphorylates the Ser-13 residue at the Golgi during intracellular protein traffic, as shown schematically in Fig. 8. Phosphorylated dual-lipid-modified Lyn and S-palmitoylated CK1γ are then transported from the Golgi to the plasma membrane.	SIGNOR-275396
P54274	Q8NA31	relocalization	up-regulates activity	0.2	The shelterin complex has six proteins, containing TRF1, TRF2, POT1, RAP1, TIN2, and TPP1. The shelterin complex is localized to the chromosome end and protects telomeric DNA (Palm and de Lange, 2008). The TTM complex acts as a “linker” and bridges the LINC and shelterin complexes together. The connection between TTM and shelterin complexes is well-known, which is mediated by TERB1 and TRF1	SIGNOR-263315
Q4G163	Q13555	phosphorylation	down-regulates activity	0.2	Activated CaMKII and polo-like kinase simultaneously phosphorylate and inactivate Emi2 [ xref , xref , xref , xref , xref ]).	SIGNOR-280200
P13498	P17252	phosphorylation	up-regulates	0.2	Phosphorylation of p22phox on threonine 147 enhances NADPH oxidase activity by promoting p47phox binding. \| Threonine 147 of p22phox Is Phosphorylated by PKC-α and PKC-δ in Vitro	SIGNOR-260891
P40337	P06493	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
O43172	P21127	phosphorylation	up-regulates activity	0.2	Furthermore, hPRP4 interacted directly with Clk1 on its COOH terminus, and the arginine and serine rich domain of hPRP4 was phosphorylated by Clk1 in vitro.\|Overexpression of Clk1 caused redistribution of hPRP4, from the speckled to the diffuse pattern in nucleoplasm, whereas inactive mutant of Clk1 caused no change of hPRP4 localization.	SIGNOR-280208
Q13131	P05771	phosphorylation	down-regulates activity	0.2	Purified PKC and Akt both phosphorylated AMPKα1 Ser487 in vitro with similar efficiency. PKC activation was associated with reduced AMPK activity, as inhibition of PKC increased AMPK activity and phorbol esters inhibited AMPK, an effect lost in cells expressing mutant AMPKα1 Ser487Ala. Consistent with a pathophysiological role for this modification, AMPKα1 Ser487 phosphorylation was inversely correlated with insulin sensitivity in human muscle.	SIGNOR-276460
Q8N257	Q14493	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-265388
Q96PX8	P68400	phosphorylation	up-regulates activity	0.2	In our studies, SICD was phosphorylated by PKA, PKC, and CK2, and association of SLITRK1 with 14-3-3 was regulated by phosphorylation at Ser695. Co-precipitation experiments demonstrated much greater recovery of 14-3-3 in SLITRK1 precipitates when wild-type or S695E was used, as compared with S695A, consistent with the results with purified peptides.	SIGNOR-273633
P09622	Q9Y572	phosphorylation	up-regulates activity	0.2	Here, we show that RIP3 activates the pyruvate dehydrogenase complex (PDC, also known as PDH), the rate-limiting enzyme linking glycolysis to aerobic respiration, by directly phosphorylating the PDC E3 subunit (PDC-E3) on T135.	SIGNOR-266372
Q99576	Q53ET0	transcriptional regulation	up-regulates quantity	0.2	CRTC2 knockdown attenuates glucocorticoid-responsive GILZ mRNA expression in HeLa cells	SIGNOR-256109
P46531	O60684	relocalization	up-regulates	0.2	Nicd binds via one of its four potential nuclear localization signals to importins alfa3, alfa4, and alfa7. importins alpha3, alpha4 (and to a lesser extent, alpha7) mediate nuclear import of nicd and thus are directly involved in notch signaling.	SIGNOR-165343
Q15796	Q9H4A3	phosphorylation	up-regulates quantity	0.2	In addition, WNK1 and WNK4 can phosphorylate Smad2, and silencing of WNK1 reduces Smad2 protein levels in HeLa cells, suggesting that WNKs have complex effects on TGFbeta signaling, which itself can promote cancer or act in a tumor suppressing manner.	SIGNOR-280164
Q13433	P43403	phosphorylation	up-regulates activity	0.2	To summarize, upon TCR triggering Zap70 activates Zip6, which is localized to the IS, through phosphorylation of tyrosine residues likely located in the long cytoplasmic loop.\|Zip6 Is Phosphorylated by Zap70 in Response to TCR Stimulation.	SIGNOR-280165
P78337	P00519	phosphorylation	up-regulates activity	0.2	Notably, c-Abl controls augmentation of Pitx1 at the post-transcriptional level.\|Overexpression of c-Abl induces tyrosine phosphorylation of Pitx1, either directly or indirectly.	SIGNOR-280171
Q13263	P12931	phosphorylation	down-regulates activity	0.2	Among SFKs, Src strongly induces tyrosine phosphorylation of KAP1.\|Immunostaining and chromatin fractionation show that Src and Lyn decrease the association of KAP1 with heterochromatin in a kinase activity-dependent manner.	SIGNOR-280137
Q7L7X3	Q9Y6E0	phosphorylation	up-regulates activity	0.2	Thus, MST3 phosphorylates TAO1 and TAO2, enabling their association with Myosin Va.	SIGNOR-280140
P35222	Q9P289	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
P10275	Q13043	phosphorylation	down-regulates activity	0.2	Here we showed that MST1 is an androgen receptor kinase and phosphorylates androgen receptor at Ser-650 ( ).\|Mst1 plays a critical role in the regulation of programmed cell death and it has been implicated in PCa development. Interestingly, MST1 has been detected in AR-chromatin complexes, and forced expression of MST1 reduces AR binding to androgen-responsive elements along the PSA promoter.	SIGNOR-280143
Q12948	Q16539	phosphorylation	up-regulates quantity by stabilization	0.2	P38 interacts with and phosphorylates the Ser241 and ser272 sites of FOXC1 to maintain its stability by inhibiting ubiquitination and degradation.	SIGNOR-275913
Q8NER1	P29350	dephosphorylation	down-regulates activity	0.2	Shp-1 dephosphorylates TRPV1 in dorsal root ganglion neurons and alleviates CFA-induced inflammatory pain in rats.\|These results suggested that Shp-1 dephosphorylated and inhibited TRPV1 in DRG neurons, contributing to maintain thermal nociceptive thresholds in normal rats, and as a compensatory mechanism, Shp-1 increased in DRGs of rats with CFA-induced inflammatory pain, which was involved in protecting against excessive thermal hyperalgesia.	SIGNOR-277129
P21589	P33981	phosphorylation	up-regulates activity	0.2	Intermolecular NTE phosphorylation by Mps1 requires a topology in which sites proximal to the NTE interact with the active Mps1 in order to promote phosphorylation.	SIGNOR-280157
Q66PJ3	Q96BR1	phosphorylation	down-regulates activity	0.2	AIP4 is phosphorylated by CISK in vitro on WW domain residues, which may impact its ability to interact with and ubiquitinate substrate proteins.\|Expression of a constitutively active CISK inhibits CXCR4 degradation, possibly by attenuating CXCR4 binding to and ubiquitination by AIP4 and/or modulating the action of AIP4 on a protein involved in CXCR4 endosomal sorting .	SIGNOR-280124
P41161	Q9H2G2	phosphorylation	up-regulates activity	0.2	Here, we report that the direct activation of the three mammalian ERMs by the Ste20-like kinase (SLK) is crucial for guiding the mitotic spindle toward the expected orientation in two mammalian models of oriented cell division: micropatterned cells and apical progenitors of the mouse neocortex.\|SLK directly phosphorylates mammalian ERMs and controls their cortical activation in mitosis.	SIGNOR-280126
Q14114	Q05519	post transcriptional regulation	up-regulates quantity by stabilization	0.2	We demonstrate that SFRS11 directly binds to the 3' UTR of LRP8 mRNA, as well as to the third exon of apoE mRNA, resulting in stabilization of these mRNAs, eventually deactivating JNK signaling.	SIGNOR-269670
P29350	Q04759	phosphorylation	down-regulates activity	0.2	SHP-1 phosphorylation is mediated through PKC-θ. Here, we show that phosphorylation of SHP-1 in NK cells on the S591 residue by PKC-θ promotes the inhibited SHP-1 'folded' state. Silencing PKC-θ maintains SHP-1 in the active conformation, reduces NK cell activation and cytotoxicity, and promotes tumor progression in vivo.	SIGNOR-277590
Q9UBR4	O75116	phosphorylation	up-regulates activity	0.2	Rok-\u03b1 phosphorylates and activates LIM kinase, which in turn phosphorylates and inactivates cofilin.	SIGNOR-280110
P09874	Q05655	phosphorylation	down-regulates activity	0.2	Interestingly, comparable experiments with the Ca 2+ -independent PKC\u03b4 isoform revealed that PKC\u03b4 phosphorylates ARTD1 at the N-terminus (amino acids 1\u2013214) and phosphorylation of ARTD1 by PKC\u03b4 inhibited DNA-induced PAR formation by ARTD1 in vitro (Supplementary Figure S6A and S6B), suggesting that the observed stimulatory effect of the PKCi on PAR formation might be due to inhibition of ARTD1 by PKC\u03b4.	SIGNOR-280085
Q6ZMZ3	Q9H3D4	transcriptional regulation	up-regulates quantity by expression	0.2	Here we show that in the developing skin, epidermal progenitor cells of mice lacking p63 transcription factor display alterations in the nuclear shape accompanied by a marked decrease in expression of several nuclear envelope-associated components (Lamin B1, Lamin A/C, Sun1, Nesprin-3, Plectin) compared with controls. Furthermore, chromatin immunoprecipitation-quantitative PCR assay showed enrichment of p63 on Sun1, Syne3, and Plec promoters, suggesting them as p63 targets.	SIGNOR-263280
P42574	Q9UBF6	ubiquitination	down-regulates activity	0.2	SAG (Sensitive to Apoptosis Gene), also known as RBX2 (RING box protein 2), ROC2 (Regulator of Cullins 2), or RNF7 (RING Finger Protein 7), was originally cloned in our laboratory as a redox inducible antioxidant protein and later characterized as the second member of the RBX/ROC RING component of the SCF (SKP1-CUL-F-box Proteins) E3 ubiquitin ligase. by forming a complex with other components of the SCF E3 ligase, SAG promotes ubiquitination and degradation of a number of protein substrates, including c-JUN, DEPTOR, HIF-1α, IκBα, NF1, NOXA, p27, and procaspase-3, thus regulating various signaling pathways and biological processes.	SIGNOR-271448
Q9BYF1	P0DTC2	binding	down-regulates activity	0.2	SARS-CoV and likely SARS-CoV-2 lead to downregulation of the ACE2 receptor, but not ACE, through binding of the spike protein with ACE2. This leads to viral entry and replication, as well as severe lung injury.	SIGNOR-260742
Q9BYF1	P59594	binding	down-regulates activity	0.2	Cell entry of severe acute respiratory syndrome coronavirus (SARS-CoV) is mediated by the viral spike (S) protein. Amino acids 319-510 on the S protein have been mapped as the receptor-binding domain (RBD), which mediates binding to the SARS-CoV receptor angiotensin converting enzyme 2 (ACE2) on SARS-CoV susceptible cells. Here, we demonstrate that the RBD spike protein alone can be internalized together with ACE2. We propose that after binding to ACE2, the RBD spike protein activates the ACE2 mediated cellular endocytosis signal pathway, by which SARS-CoV enters the susceptible cells.	SIGNOR-260283
O14713	O96013	phosphorylation	down-regulates activity	0.2	We further demonstrate that p21 activated kinase 4 (PAK4) can phosphorylate ICAP1 at Ser 10 both in vitro and in cultured cells, and that active PAK4 inhibits ICAP1 nuclear accumulation in a Ser-10-dependent manner.\|We further demonstrate that p21-activated kinase 4 (PAK4) can phosphorylate ICAP1 at Ser-10 both in vitro and in cultured cells, and that active PAK4 inhibits ICAP1 nuclear accumulation in a Ser-10-dependent manner.	SIGNOR-280056
P08134	Q9NQU5	phosphorylation	down-regulates activity	0.2	It is possible that Pak6 may directly phosphorylate RhoC to regulate its activity.\|Nevertheless, our results clearly show that the kinase activity of Pak6 is required to inhibit RhoC induced cell contraction.	SIGNOR-280059
P48431	Q9NQU5	phosphorylation	up-regulates quantity	0.2	PAK5 promotes the cell stemness ability by phosphorylating SOX2 in lung squamous cell carcinomas.\|The absence of PAK5 abolishes self-renewal ability of LUSC cells by decreasing the expression and phosphorylation of SOX2 in vitro and in vivo.	SIGNOR-280060
Q969V6	Q16512	phosphorylation	down-regulates activity	0.2	Although RHOA mediated actin polymerization accelerated MRTFA induced gene transcription, PKN1 and PKN2 inhibited the interaction of MRTFA with G-actin by phosphorylating MRTFA, causing increased serum response factor (SRF)-mediated expression of cardiac hypertrophy- and fibrosis associated genes.\|Further, we identified MRTFA as a novel substrate of PKN1 and PKN2 and found that MRTFA phosphorylation by PKN was considerably more effective than that by ROCK in vitro .	SIGNOR-280067
P16104	Q9H4B4	phosphorylation	up-regulates activity	0.2	Phosphorylation of H2AX at serine 139 was catalyzed by hyperosmotic stress-induced activation of Plk3.\|Osmotic stress induced phosphorylation of H2AX by polo like kinase 3 affects cell cycle progression in human corneal epithelial cells.\|Our results for the first time reveal that hyperosmotic stress-activated Plk3 elicited \u03b3H2AX.	SIGNOR-280073
Q99878	Q9Y4B6	phosphorylation	up-regulates activity	0.2	Here we report that VprBP possesses an intrinsic protein kinase activity and is capable of phosphorylating histone H2A on threonine 120 (H2AT120p) in a nucleosomal context. Functional studies reveal that H2AT120p by VprBP is sufficient to repress chromatin transcription.	SIGNOR-279884
P30305	P17612	phosphorylation	up-regulates activity	0.2	Overall, PRKACA may directly phosphorylate CDC25B on Ser321 to control cell cycle progression in mouse-fertilized eggs [ xref ].\|PRKACA phosphorylates and activates CDC25B in fertilized eggs of mice [ xref ].	SIGNOR-280077
O15511	P17252	phosphorylation	up-regulates activity	0.2	PKC\u03b1 phosphorylates and activates ARPC5, which organizes the actin net dorsolateral of nucleus.	SIGNOR-280078
P29474	P41743	phosphorylation	down-regulates activity	0.2	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-251635
Q9Y6M1	P42345	phosphorylation	up-regulates activity	0.2	IGF2BP2 can be activated by mTOR and promotes its binding to IGF2 mRNA of IGF2 thereby leading to diabetes mellitus [ xref , xref ].\|In addition, phosphorylation of IGF2BP2 in the linker region between RRM2 and KH1 by mTOR promotes its binding to the IGF leader 3 mRNA 5\u2032-UTR, enhancing the initiation of IGF2 translation through eIF-4E- and 5\u2032 cap-independent internal ribosomal entry [ xref ].	SIGNOR-280046
O43561	Q9H093	phosphorylation	down-regulates activity	0.2	Analysis by an in vitro kinase assay revealed that NUAK2 could phosphorylate immunoprecipitated LATS and that this phosphorylation was lost in the LATS double mutant (DM), T246A/S613A (Fig.\u00a0 xref ).\|We showed that phosphorylation of Ser613, located upstream of the KD, adjacent to the MOB binding site and to a lesser extent the N-terminal localized T246, are required for NUAK2 to inhibit LATS.	SIGNOR-280052
P23975	Q13153	phosphorylation	down-regulates activity	0.2	PAK1 negatively regulates the activity of the Rho exchange factor NET1.\|Specifically, PAK1 phosphorylates NET1 on three sites in vitro : serines 152, 153, and 538.	SIGNOR-280054
P17676	O96013	phosphorylation	up-regulates activity	0.2	Importantly, we found that PAK4 enhanced CEBPB phosphorylation on Thr 235.\|In summary, we showed that PAK4 mediated CEBPB activation upregulated CLDN4 expression to promote breast cancer cell migration and invasion.	SIGNOR-280055
Q13501	Q9UK99	binding	down-regulates quantity by destabilization	0.2	F-box protein Fbxo3 targets Smurf1 ubiquitin ligase for ubiquitination and degradation. Here we show that another F-box protein Fbxo3, belonging to the FBXO type protein family, also interacts with and targets Smurf1 for poly-ubiquitination and proteasomal degradation. The SCF complex is composed of F-box protein, Skp1, Cullin1 (Cul1) and ROC1. Fbxo3, whose substrates are few, forms SCF Fbxo3 ubiquitin ligase and regulates the degradations of Fbxl2, p62, HIPK2 and p300 through the ubiquitin-proteasome pathway.	SIGNOR-272444
Q9UBK2	P49760	phosphorylation	down-regulates activity	0.2	Clk2 could also repress PGC-1alpha activation of Foxo1 on the IRS response element , as well as repress the Pepck promoter .\|Clk2 phosphorylates and represses PGC-1\u03b1.	SIGNOR-278228
Q9NS28	P17612	phosphorylation	up-regulates activity	0.2	Cyclic AMP- and cyclic GMP-dependent kinases (PKA, PKG) inhibit the interaction of RGS18 and 14-3-3 by phosphorylating S216.	SIGNOR-273786
O43426	Q9P286	phosphorylation	up-regulates activity	0.2	We identified two novel Pak5 substrates, Pacsin1 and Synaptojanin1, proteins that directly interact with one another to regulate synaptic vesicle endocytosis and recycling. Pacsin1 and Synaptojanin1 were phosphorylated by Pak5 and the other group II Paks in vitro, and Pak5 phosphorylation promoted Pacsin1-Synaptojanin1 binding both in vitro and in vivo.	SIGNOR-263026
Q2M3R5	Q8IXL6	phosphorylation	up-regulates activity	0.2	Notably, phosphorylation of Stim1 by Fam20C enhances Stim1 activation and store-operated Ca 2+ entry.\|We feel that the western blot shows an appropriate range of contrast to support the conclusion that Stim1 can be activated by Fam20C under high calcium conditions.	SIGNOR-280012
Q9H300	Q15119	phosphorylation	up-regulates activity	0.2	As expected, knocking down PDK2 in HEK293 cells that overexpress PARL resulted in a significant increase in beta cleavage in comparison to the control cells.\|Furthermore, we show that PDK2, a key regulator in metabolic plasticity, phosphorylates PARL and regulates \u03b2 cleavage.	SIGNOR-280018
P30281	Q15759	phosphorylation	down-regulates quantity by destabilization	0.2	P38SAPK2 phosphorylates cyclin D3 at Thr-283 and targets it for proteasomal degradation.	SIGNOR-280023

P08237

O60502

0

deglycosylation

up-regulates activity

0.2

Our previous investigation on O-GlcNAcylation of PFK1 has demonstrated that O-GlcNAcylation inhibits PFK1 enzyme activity|In cells, a single set of antagonistic enzymes-O-GlcNAc transferase (OGT) and O-GlcNAc hydrolase are responsible for the addition and removal of GlcNAc moiety, respectively.

SIGNOR-267607

O60260

P62987

0

binding

up-regulates activity

0.2

The phosphorylation-dependent interaction between ubiquitin and parkin suggests that phosphorylated ubiquitin unlocks autoinhibition of the catalytic cysteine. Our results show that PINK1-dependent phosphorylation of both parkin and ubiquitin is sufficient for full activation of parkin E3 activity. These findings demonstrate that phosphorylated ubiquitin is a parkin activator.

SIGNOR-270344

Q4ZG55

Q14686

0

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

Q9NPD5

P53567

0

transcriptional regulation

up-regulates quantity by expression

0.2

Taken together, these findings suggest that the LPS-induced down-regulation of Oatp4 is likely due to reduction in the binding of HNF1alpha, C/EBP, HNF3, and RXR:RAR to the Oatp4 promoter.

SIGNOR-268986

Q9UKV5

Q92890

0

binding

up-regulates activity

0.2

Here we show that Ufd1 directly interacts with gp78 and functions as a cofactor. Ufd1 enhances the E3 activity of gp78, accelerates the ubiquitination and degradation of reductase, and eventually promotes receptor-mediated uptake of low-density lipoprotein.

SIGNOR-252425

Q99828

Q9UNE7

0

ubiquitination

down-regulates quantity

0.2

All those were suggesting that CHIP promotes CIB1 ubiquitination via the Lys 48 residue of ubiquitin.|K10 and K65 were the Lysine (K) residues for CHIP mediated CIB1 degradation.

SIGNOR-278721

P42263

Q9BYB0

0

binding

up-regulates quantity

0.2

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

SIGNOR-264603

O75385

P14373

0

ubiquitination

down-regulates quantity

0.2

STK38L ubiquitination promotes its activation and phosphorylation of ULK1 at Ser495, rendering ULK1 in a permissive state for TRIM27-mediated hyper-ubiquitination

SIGNOR-270349

Q9BZI1

P27361

0

phosphorylation

up-regulates activity

0.2

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

SIGNOR-263061

Q9NPD5

P42229

0

transcriptional regulation

up-regulates quantity by expression

0.2

PRL enhanced the binding of Stat5a to the OATP1B3 promoter and DNA-protein binding was inhibited in competition assays by excess OATP1B3 and Stat5 consensus oligomers but not by mutant Stat5 oligomers.|PRL and GH induction of Oatp1b2 and OATP1B3 promoter activity required cotransfection of Stat5a and PRLRL or GHR.

SIGNOR-268990

Q86YD1

Q96BR1

0

phosphorylation

down-regulates quantity by destabilization

0.2

In this study, we find that the understudied serum and glucocorticoid-induced kinase-2 (SGK2) phosphorylates PTOV1 at S36.

SIGNOR-279283

E9PAV3

P49841

0

phosphorylation

down-regulates

0.2

Gsk3 beta-dependent phosphorylation of the alpha nac coactivator regulates its nuclear translocation and proteasome-mediated degradation.

SIGNOR-123262

Q8IYW5

P0C0S8

0

binding

up-regulates

0.2

Rnf168 is recruited to sites of dna damage by binding to ubiquitylated histone h2a.

SIGNOR-183890

Q01105

Q9UBY8

0

binding

down-regulates activity

0.2

CLN8 interacts with ceramide binding proteins PP2A and I2PP2A. We showed that the phosphorylation levels of several substrates of PP2A, namely Akt, S6 kinase, and GSK3β, were decreased in CLN8 disease patient fibroblasts. This reduction can be reversed by inhibiting PP2A phosphatase activity with cantharidin, suggesting a higher PP2A activity in CLN8-deficient cells. The phosphorylation levels of PP2A substrates are decreased in the absence of CLN8.

SIGNOR-265584

Q16695

Q9Y4C1

0

demethylation

up-regulates activity

0.2

Using a biochemical assay coupled with chromatography, we have purified a JmjC domain-containing protein, JHDM2A, which specifically demethylates mono- and dimethyl-H3K9.

SIGNOR-276846

Q16611

P54829

0

dephosphorylation

up-regulates activity

0.2

In this study, we report that on apoptotic stimulation Bak undergoes dephosphorylation at tyrosine residue 108 (Y108), a critical event that is necessary but not sufficient for Bak activation, but is required both for early exposure of the occluded N-terminal domain and multimerisation.

SIGNOR-248542

Q9NRM7

P17612

0

phosphorylation

up-regulates

0.2

Here, we show that cyclic amp (camp)-dependent protein kinase (pka) phosphorylates lats and thereby enhances its activity sufficiently to phosphorylate yap on ser381.

SIGNOR-236994

O00560

P59637

0

relocalization

up-regulates activity

0.2

Overall, these results support the hypothesis that the interaction of E protein PBM with syntenin facilitates the recruitment of syntenin in the cytosol and leads to p38 MAPK activation.

SIGNOR-260752

O14558

P17612

0

phosphorylation

down-regulates

0.2

Hosphorylation of hsp20 at ser16 is not only associated with cyclic nucleotide-dependent vasorelaxation but also inhibits agonist-induced contractile responses.

SIGNOR-66493

Q8TDY4

P00533

0

phosphorylation

up-regulates activity

0.2

How ACAP4 regulates membrane dynamics and curvature in response to EGF stimulation is unknown. Here, we show that phosphorylation of the N-terminal region of ACAP4, named the Bin, Amphiphysin, and RSV161/167 (BAR) domain, at Tyr34 is necessary for EGF-elicited membrane remodeling. |EGF stimulation of cells causes phosphorylation of ACAP4 at Tyr34, which subsequently promotes ACAP4 homodimer curvature.

SIGNOR-272234

Q9UQ26

O95153

0

binding

down-regulates activity

0.2

SH3 domains of RBPs interact with RIMs. The enhancement of depolarization-induced secretion in PC12 cells by fusion proteins that suppress the associations of RBPs with RIMs and α1 suggests that RBPs may repress RIMs, either directly or through associated proteins.

SIGNOR-264368

O14950

Q12852

0

phosphorylation

up-regulates

0.2

Zip kinase (hzipk) phosphorylated the regulatory light chain of myosin ii (mrlc) at both ser19 and thr18 in vitro. In this study, we demonstrate that hzipk also induces the diphosphorylation of mrlc in nonmuscle cells.

SIGNOR-113664

P31751

P24666

0

dephosphorylation

down-regulates activity

0.2

Reduction in the levels of both LMW-PTP isoforms in vitro and in vivo increased tyrosine phosphorylation of IR and AktSer473 and increased IRS-1- and IRS-2-associated PI3-K activities in both liver and fat.|Activated PI3-K stimulates Akt (or protein kinase B) that in turn phosphorylates and inactivates glycogen synthase kinase-3

SIGNOR-248456

P69905

P17509

0

transcriptional regulation

down-regulates quantity by repression

0.2

HOXB6 protein represses globin transcript levels in stably transfected K562 cells in a DNA-binding dependent fashion.

SIGNOR-261637

Q9NQA5

P17252

0

phosphorylation

up-regulates activity

0.2

A cell permeable analog of DAG increased TRPV5 activity within 30 min via protein kinase C activation of the channel since mutation of TRPV5 at the putative PKC phosphorylation sites S299 and S654 prevented the stimulatory effect of TK.

SIGNOR-149948

Q8TB45

P43405

0

phosphorylation

down-regulates activity

0.2

We found that tyrosine (Tyr) 289 phosphorylation of DEPTOR impairs its interaction with mTOR, leading to increased mTOR activation. Using proximity biotinylation assays, we identified SYK (spleen tyrosine kinase) as a kinase involved in DEPTOR Tyr 289 phosphorylation in an ephrin (erythropoietin-producing hepatocellular carcinoma) receptor-dependent manner.

SIGNOR-277572

P11908

Q13131

0

phosphorylation

down-regulates activity

0.2

We demonstrate here that glucose deprivation or hypoxia results in the AMPK-mediated phosphorylation of phosphoribosyl pyrophosphate synthetase 1 (PRPS1) S180 and PRPS2 S183, leading to conversion of PRPS hexamers to monomers and thereby inhibiting PRPS1/2 activity, nucleotide synthesis, and nicotinamide adenine dinucleotide (NAD) production.

SIGNOR-265731

Q9NYY3

Q9P253

0

ubiquitination

down-regulates quantity by destabilization

0.2

VPS18 Ubiquitylates SNK in Vitro and in Vivo. The ubiquitylation of proteins by hVPS18 was selectively mediated by UbcH4.

SIGNOR-271550

P11413

Q05655

0

phosphorylation

up-regulates

0.2

A pkc activator, significantly increased g6pd phosphorylation and activity, whereas single (s210a, t266a) and double (s210a/t266a) mutations at sites flanking the g6pd active site significantly inhibited phosphorylation, shifted the isoelectric point, and reduced enzyme activity.

SIGNOR-167053

Q99523

Q13177

0

phosphorylation

down-regulates activity

0.2

PAKs specifically phosphorylate Ser15 of the sortilin-cd and alter its trafficking. It can be concluded that PAK1-3 may indeed instigate the phosphorylation of sortilin and that they target a single serine residue (Ser15) located in the kinase domain-binding site of the sortilin-cd. Full-length sortilins with the serine at position 793 (residue 15 in the cytoplasmic domain) (for the sequence, see Fig. 2). Phosphorylation (Ser15) downregulates the sortilin–AP-1 interaction.

SIGNOR-273717

Q9H2X6

P54646

0

phosphorylation

down-regulates activity

0.2

AMPKalpha2-mediated inhibition of WIP1 phosphorylation by HIPK2|Site-directed mutagenesis of Thr112 and Ser114 in the N terminus, and Thr1107 in the C terminus markedly reduced HIPK2 phosphorylation by AMPKalpha2 in vitro

SIGNOR-275485

Q32MZ4

P43405

0

phosphorylation

up-regulates activity

0.2

However, this inhibitory activity TRIP can be reversed by the co-expression of Syk, which might inhibit the activity of cytoplasmic TRIP, sequester TRIP from important nucleolar targets or even counter TRIP 's inhibitory effects on TRAF and TNF signaling by regulating the activity of alternative components of the pathway.|Syk induces phosphorylation of TRIP on tyrosine.

SIGNOR-279297

Q15375

P56915

0

transcriptional regulation

down-regulates quantity by repression

0.2

We demonstrate that Goosecoid can act as a repressor of its own promoter activity in transient co-transfection experiments in mouse P19 cells and in Xenopus embryos. Autorepression depends on the presence of the homeodomain and is mediated through the prd element more proximal to the transcriptional start site.

SIGNOR-261613

P04234

O60858

0

polyubiquitination

down-regulates quantity by destabilization

0.2

RFP2, a gene frequently lost in various malignancies, encodes a protein with RING finger, B-box, and coiled-coil domains that belongs to the RBCC/TRIM family of proteins.Rfp2 Regulates the Stability of the ERAD Substrate CD3-δ. In summary, these experiments demonstrate that Rfp2 functions as a RING-dependent ERAD E3 ubiquitin ligase and regulates the degradation of the ER substrate, CD3-δ.

SIGNOR-271644

P48050

P17252

0

phosphorylation

down-regulates activity

0.2

These results therefore indicate that Kir2.3 is directly modulated by PKC phosphorylation of its channel protein and threonine 53 is the PKC phosphorylation site in Kir2.3.

SIGNOR-275965

P10412

Q96GD4

0

phosphorylation

up-regulates quantity by stabilization

0.2

we showed previously that phosphorylation of S27 in human histone H1.4 (H1.4S27-P), prevents binding of heterochromatin protein 1 (HP1) family members (officially known as chromobox protein homologs) to the neighboring dimethylated K26. Here, we present the first functional characterization of H1.4S27-P in vivo and in vitro. We show that H1.4S27 phosphorylation is cell-cycle-regulated and its levels peak on metaphase chromosomes. We identify further Aurora B as the kinase phosphorylating H1.4S27.

SIGNOR-262658

P07195

Q9NXA8

0

deacetylation

up-regulates activity

0.2

In colorectal cancer, SIRT5 binds to lactate dehydrogenase B (LDHB) to deacetylate it at Lysine 329, thereby increasing its enzymatic activity.

SIGNOR-267645

P04406

Q5XX13

0

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

O75962

Q00535

0

phosphorylation

up-regulates activity

0.2

Roscovitine inhibits the ability of Trio to activate Rac, and peptides corresponding to the Cdk5 consensus sites in Trio are phosphorylated by Cdk5.|Together, these data suggest that control of the cortical actin cytoskeleton, long known to modulate hormone exocytosis and subsequent endocytosis, involves Cdk5 mediated activation of Trio.

SIGNOR-280220

P47989

Q00535

0

phosphorylation

up-regulates activity

0.2

Finally, threonine 222 of XOR is the critical target site for CDK5 dependent activation of XOR.|Once we determined CDK5 was necessary for hypoxia induced hyperactivation of XOR, we tested whether CDK5 was sufficient to phosphorylate XOR and induce increased enzymatic activity in a cell free system.

SIGNOR-280221

Q9HAU4

Q13315

0

phosphorylation

up-regulates activity

0.2

Using biochemical approaches and MS analysis, we show that upon the onset of the DNA-damage response, SMURF2 becomes phosphorylated at Ser384 by ataxia telangiectasia mutated (ATM) serine/threonine kinase, and this phosphorylation is required for its interaction with RNF20.

SIGNOR-277534

P11908

Q9UHD2

0

phosphorylation

up-regulates activity

0.2

Here, we show that ionizing radiation results in TBK1-mediated phosphorylation of phosphoribosyl pyrophosphate synthetase (PRPS)1/2 at T228, thereby enhancing PRPS1/2 catalytic activity and promoting deoxyribonucleotide synthesis.

SIGNOR-277317

P68431

O15054

0

demethylation

down-regulates activity

0.2

Ubiquitously Transcribed Tetratricopeptide Repeat on chromosome X (UTX) and Jumonji D3 (JMJD3) as novel histone demethylases that catalyze the removal of di- and trimethyl groups on histone H3 lysine 27, thereby promoting target gene activation.

SIGNOR-260018

P11308

P48730

0

phosphorylation

down-regulates activity

0.2

Interestingly, only CKId, but not other CKI isoforms or CKII could promote ERG degradation under ectopic expression conditions (XREF_FIG).|These results indicate that phosphorylation of ERG by CKIdelta within the SPOP-recognition degron triggers its interaction with SPOP to promote ERG destruction .

SIGNOR-280234

P09471

P47900

0

binding

up-regulates activity

0.2

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

SIGNOR-257185

Q9BXF6

Q15208

0

phosphorylation

up-regulates activity

0.2

We identified 5 potential NDR1 substrates in the mouse brain and chose two for functional validation. We show that one NDR1 substrate is another kinase, AP-2 associated kinase-1 (AAK1) which regulates dendritic branching as a result of NDR1 phosphorylation. Another substrate is the Rab8 guanine nucleotide exchange factor (GEF) Rabin8 (a Sec2p homolog) which we find is involved in spine synapse formation.

SIGNOR-263035

Q9Y458

P14921

0

transcriptional regulation

up-regulates quantity by expression

0.2

TBX22 is an X-linked gene, which encodes a T-box-containing transcription factor. Loss-of-function mutation in the X-linked TBX22 promoter disrupts an ETS-1 binding site and leads to cleft palate. We first link the transcription factor ETS-1 to TBX22 pathway during embryonic palatogenesis.

SIGNOR-265565

P53350

Q9BTA9

0

binding

up-regulates activity

0.2

Here, we report that the activation of Plk1 requires WAC, a WW domain-containing adaptor protein with a coiled-coil region that predominantly localizes to the nucleus in interphase. Cyclin-dependent kinase 1 (Cdk1) phosphorylates WAC, priming its direct interaction with the polo-box domain of Plk1.

SIGNOR-265036

P07948

Q9HCP0

0

phosphorylation

up-regulates quantity by stabilization

0.2

Although there have been more than 40 reports of mass spectrometric studies on phosphorylation at Lyn-S13, the kinase responsible remained unclear. We succeeded in identifying casein kinase 1γ (CK1γ) as the kinase responsible for phosphorylation of Lyn-S13. In HEK293 cells co-expressing Lyn and CK1γ, the phosphorylation level of Lyn-S13 increased significantly. we concluded that S-palmitoylated CK1γ encounters N-myristoylated Lyn and specifically phosphorylates the Ser-13 residue at the Golgi during intracellular protein traffic, as shown schematically in Fig. 8. Phosphorylated dual-lipid-modified Lyn and S-palmitoylated CK1γ are then transported from the Golgi to the plasma membrane.

SIGNOR-275396

P54274

Q8NA31

0

relocalization

up-regulates activity

0.2

The shelterin complex has six proteins, containing TRF1, TRF2, POT1, RAP1, TIN2, and TPP1. The shelterin complex is localized to the chromosome end and protects telomeric DNA (Palm and de Lange, 2008). The TTM complex acts as a “linker” and bridges the LINC and shelterin complexes together. The connection between TTM and shelterin complexes is well-known, which is mediated by TERB1 and TRF1

SIGNOR-263315

Q4G163

Q13555

0

phosphorylation

down-regulates activity

0.2

Activated CaMKII and polo-like kinase simultaneously phosphorylate and inactivate Emi2 [ xref , xref , xref , xref , xref ]).

SIGNOR-280200

P13498

P17252

0

phosphorylation

up-regulates

0.2

Phosphorylation of p22phox on threonine 147 enhances NADPH oxidase activity by promoting p47phox binding. | Threonine 147 of p22phox Is Phosphorylated by PKC-α and PKC-δ in Vitro

SIGNOR-260891

P40337

P06493

0

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

O43172

P21127

0

phosphorylation

up-regulates activity

0.2

Furthermore, hPRP4 interacted directly with Clk1 on its COOH terminus, and the arginine and serine rich domain of hPRP4 was phosphorylated by Clk1 in vitro.|Overexpression of Clk1 caused redistribution of hPRP4, from the speckled to the diffuse pattern in nucleoplasm, whereas inactive mutant of Clk1 caused no change of hPRP4 localization.

SIGNOR-280208

Q13131

P05771

0

phosphorylation

down-regulates activity

0.2

Purified PKC and Akt both phosphorylated AMPKα1 Ser487 in vitro with similar efficiency. PKC activation was associated with reduced AMPK activity, as inhibition of PKC increased AMPK activity and phorbol esters inhibited AMPK, an effect lost in cells expressing mutant AMPKα1 Ser487Ala. Consistent with a pathophysiological role for this modification, AMPKα1 Ser487 phosphorylation was inversely correlated with insulin sensitivity in human muscle.

SIGNOR-276460

Q8N257

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-265388

Q96PX8

P68400

0

phosphorylation

up-regulates activity

0.2

In our studies, SICD was phosphorylated by PKA, PKC, and CK2, and association of SLITRK1 with 14-3-3 was regulated by phosphorylation at Ser695. Co-precipitation experiments demonstrated much greater recovery of 14-3-3 in SLITRK1 precipitates when wild-type or S695E was used, as compared with S695A, consistent with the results with purified peptides.

SIGNOR-273633

P09622

Q9Y572

0

phosphorylation

up-regulates activity

0.2

Here, we show that RIP3 activates the pyruvate dehydrogenase complex (PDC, also known as PDH), the rate-limiting enzyme linking glycolysis to aerobic respiration, by directly phosphorylating the PDC E3 subunit (PDC-E3) on T135.

SIGNOR-266372

Q99576

Q53ET0

0

transcriptional regulation

up-regulates quantity

0.2

CRTC2 knockdown attenuates glucocorticoid-responsive GILZ mRNA expression in HeLa cells

SIGNOR-256109

P46531

O60684

0

relocalization

up-regulates

0.2

Nicd binds via one of its four potential nuclear localization signals to importins alfa3, alfa4, and alfa7. importins alpha3, alpha4 (and to a lesser extent, alpha7) mediate nuclear import of nicd and thus are directly involved in notch signaling.

SIGNOR-165343

Q15796

Q9H4A3

0

phosphorylation

up-regulates quantity

0.2

In addition, WNK1 and WNK4 can phosphorylate Smad2, and silencing of WNK1 reduces Smad2 protein levels in HeLa cells, suggesting that WNKs have complex effects on TGFbeta signaling, which itself can promote cancer or act in a tumor suppressing manner.

SIGNOR-280164

Q13433

P43403

0

phosphorylation

up-regulates activity

0.2

To summarize, upon TCR triggering Zap70 activates Zip6, which is localized to the IS, through phosphorylation of tyrosine residues likely located in the long cytoplasmic loop.|Zip6 Is Phosphorylated by Zap70 in Response to TCR Stimulation.

SIGNOR-280165

P78337

P00519

0

phosphorylation

up-regulates activity

0.2

Notably, c-Abl controls augmentation of Pitx1 at the post-transcriptional level.|Overexpression of c-Abl induces tyrosine phosphorylation of Pitx1, either directly or indirectly.

SIGNOR-280171

Q13263

P12931

0

phosphorylation

down-regulates activity

0.2

Among SFKs, Src strongly induces tyrosine phosphorylation of KAP1.|Immunostaining and chromatin fractionation show that Src and Lyn decrease the association of KAP1 with heterochromatin in a kinase activity-dependent manner.

SIGNOR-280137

Q7L7X3

Q9Y6E0

0

phosphorylation

up-regulates activity

0.2

Thus, MST3 phosphorylates TAO1 and TAO2, enabling their association with Myosin Va.

SIGNOR-280140

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

P10275

Q13043

0

phosphorylation

down-regulates activity

0.2

Here we showed that MST1 is an androgen receptor kinase and phosphorylates androgen receptor at Ser-650 ( ).|Mst1 plays a critical role in the regulation of programmed cell death and it has been implicated in PCa development. Interestingly, MST1 has been detected in AR-chromatin complexes, and forced expression of MST1 reduces AR binding to androgen-responsive elements along the PSA promoter.

SIGNOR-280143

Q12948

Q16539

0

phosphorylation

up-regulates quantity by stabilization

0.2

P38 interacts with and phosphorylates the Ser241 and ser272 sites of FOXC1 to maintain its stability by inhibiting ubiquitination and degradation.

SIGNOR-275913

Q8NER1

P29350

0

dephosphorylation

down-regulates activity

0.2

Shp-1 dephosphorylates TRPV1 in dorsal root ganglion neurons and alleviates CFA-induced inflammatory pain in rats.|These results suggested that Shp-1 dephosphorylated and inhibited TRPV1 in DRG neurons, contributing to maintain thermal nociceptive thresholds in normal rats, and as a compensatory mechanism, Shp-1 increased in DRGs of rats with CFA-induced inflammatory pain, which was involved in protecting against excessive thermal hyperalgesia.

SIGNOR-277129

P21589

P33981

0

phosphorylation

up-regulates activity

0.2

Intermolecular NTE phosphorylation by Mps1 requires a topology in which sites proximal to the NTE interact with the active Mps1 in order to promote phosphorylation.

SIGNOR-280157

Q66PJ3

Q96BR1

0

phosphorylation

down-regulates activity

0.2

AIP4 is phosphorylated by CISK in vitro on WW domain residues, which may impact its ability to interact with and ubiquitinate substrate proteins.|Expression of a constitutively active CISK inhibits CXCR4 degradation, possibly by attenuating CXCR4 binding to and ubiquitination by AIP4 and/or modulating the action of AIP4 on a protein involved in CXCR4 endosomal sorting .

SIGNOR-280124

P41161

Q9H2G2

0

phosphorylation

up-regulates activity

0.2

Here, we report that the direct activation of the three mammalian ERMs by the Ste20-like kinase (SLK) is crucial for guiding the mitotic spindle toward the expected orientation in two mammalian models of oriented cell division: micropatterned cells and apical progenitors of the mouse neocortex.|SLK directly phosphorylates mammalian ERMs and controls their cortical activation in mitosis.

SIGNOR-280126

Q14114

Q05519

0

post transcriptional regulation

up-regulates quantity by stabilization

0.2

We demonstrate that SFRS11 directly binds to the 3' UTR of LRP8 mRNA, as well as to the third exon of apoE mRNA, resulting in stabilization of these mRNAs, eventually deactivating JNK signaling.

SIGNOR-269670

P29350

Q04759

0

phosphorylation

down-regulates activity

0.2

SHP-1 phosphorylation is mediated through PKC-θ. Here, we show that phosphorylation of SHP-1 in NK cells on the S591 residue by PKC-θ promotes the inhibited SHP-1 'folded' state. Silencing PKC-θ maintains SHP-1 in the active conformation, reduces NK cell activation and cytotoxicity, and promotes tumor progression in vivo.

SIGNOR-277590

Q9UBR4

O75116

0

phosphorylation

up-regulates activity

0.2

Rok-\u03b1 phosphorylates and activates LIM kinase, which in turn phosphorylates and inactivates cofilin.

SIGNOR-280110

P09874

Q05655

0

phosphorylation

down-regulates activity

0.2

Interestingly, comparable experiments with the Ca 2+ -independent PKC\u03b4 isoform revealed that PKC\u03b4 phosphorylates ARTD1 at the N-terminus (amino acids 1\u2013214) and phosphorylation of ARTD1 by PKC\u03b4 inhibited DNA-induced PAR formation by ARTD1 in vitro (Supplementary Figure S6A and S6B), suggesting that the observed stimulatory effect of the PKCi on PAR formation might be due to inhibition of ARTD1 by PKC\u03b4.

SIGNOR-280085

Q6ZMZ3

Q9H3D4

0

transcriptional regulation

up-regulates quantity by expression

0.2

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

SIGNOR-263280

P42574

Q9UBF6

0

ubiquitination

down-regulates activity

0.2

SAG (Sensitive to Apoptosis Gene), also known as RBX2 (RING box protein 2), ROC2 (Regulator of Cullins 2), or RNF7 (RING Finger Protein 7), was originally cloned in our laboratory as a redox inducible antioxidant protein and later characterized as the second member of the RBX/ROC RING component of the SCF (SKP1-CUL-F-box Proteins) E3 ubiquitin ligase. by forming a complex with other components of the SCF E3 ligase, SAG promotes ubiquitination and degradation of a number of protein substrates, including c-JUN, DEPTOR, HIF-1α, IκBα, NF1, NOXA, p27, and procaspase-3, thus regulating various signaling pathways and biological processes.

SIGNOR-271448

Q9BYF1

P0DTC2

0

binding

down-regulates activity

0.2

SARS-CoV and likely SARS-CoV-2 lead to downregulation of the ACE2 receptor, but not ACE, through binding of the spike protein with ACE2. This leads to viral entry and replication, as well as severe lung injury.

SIGNOR-260742

Q9BYF1

P59594

0

binding

down-regulates activity

0.2

Cell entry of severe acute respiratory syndrome coronavirus (SARS-CoV) is mediated by the viral spike (S) protein. Amino acids 319-510 on the S protein have been mapped as the receptor-binding domain (RBD), which mediates binding to the SARS-CoV receptor angiotensin converting enzyme 2 (ACE2) on SARS-CoV susceptible cells. Here, we demonstrate that the RBD spike protein alone can be internalized together with ACE2. We propose that after binding to ACE2, the RBD spike protein activates the ACE2 mediated cellular endocytosis signal pathway, by which SARS-CoV enters the susceptible cells.

SIGNOR-260283

O14713

O96013

0

phosphorylation

down-regulates activity

0.2

We further demonstrate that p21 activated kinase 4 (PAK4) can phosphorylate ICAP1 at Ser 10 both in vitro and in cultured cells, and that active PAK4 inhibits ICAP1 nuclear accumulation in a Ser-10-dependent manner.|We further demonstrate that p21-activated kinase 4 (PAK4) can phosphorylate ICAP1 at Ser-10 both in vitro and in cultured cells, and that active PAK4 inhibits ICAP1 nuclear accumulation in a Ser-10-dependent manner.

SIGNOR-280056

P08134

Q9NQU5

0

phosphorylation

down-regulates activity

0.2

It is possible that Pak6 may directly phosphorylate RhoC to regulate its activity.|Nevertheless, our results clearly show that the kinase activity of Pak6 is required to inhibit RhoC induced cell contraction.

SIGNOR-280059

P48431

Q9NQU5

0

phosphorylation

up-regulates quantity

0.2

PAK5 promotes the cell stemness ability by phosphorylating SOX2 in lung squamous cell carcinomas.|The absence of PAK5 abolishes self-renewal ability of LUSC cells by decreasing the expression and phosphorylation of SOX2 in vitro and in vivo.

SIGNOR-280060

Q969V6

Q16512

0

phosphorylation

down-regulates activity

0.2

Although RHOA mediated actin polymerization accelerated MRTFA induced gene transcription, PKN1 and PKN2 inhibited the interaction of MRTFA with G-actin by phosphorylating MRTFA, causing increased serum response factor (SRF)-mediated expression of cardiac hypertrophy- and fibrosis associated genes.|Further, we identified MRTFA as a novel substrate of PKN1 and PKN2 and found that MRTFA phosphorylation by PKN was considerably more effective than that by ROCK in vitro .

SIGNOR-280067

P16104

Q9H4B4

0

phosphorylation

up-regulates activity

0.2

Phosphorylation of H2AX at serine 139 was catalyzed by hyperosmotic stress-induced activation of Plk3.|Osmotic stress induced phosphorylation of H2AX by polo like kinase 3 affects cell cycle progression in human corneal epithelial cells.|Our results for the first time reveal that hyperosmotic stress-activated Plk3 elicited \u03b3H2AX.

SIGNOR-280073

Q99878

Q9Y4B6

0

phosphorylation

up-regulates activity

0.2

Here we report that VprBP possesses an intrinsic protein kinase activity and is capable of phosphorylating histone H2A on threonine 120 (H2AT120p) in a nucleosomal context. Functional studies reveal that H2AT120p by VprBP is sufficient to repress chromatin transcription.

SIGNOR-279884

P30305

P17612

0

phosphorylation

up-regulates activity

0.2

Overall, PRKACA may directly phosphorylate CDC25B on Ser321 to control cell cycle progression in mouse-fertilized eggs [ xref ].|PRKACA phosphorylates and activates CDC25B in fertilized eggs of mice [ xref ].

SIGNOR-280077

O15511

P17252

0

phosphorylation

up-regulates activity

0.2

PKC\u03b1 phosphorylates and activates ARPC5, which organizes the actin net dorsolateral of nucleus.

SIGNOR-280078

P29474

P41743

0

phosphorylation

down-regulates activity

0.2

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-251635

Q9Y6M1

P42345

0

phosphorylation

up-regulates activity

0.2

IGF2BP2 can be activated by mTOR and promotes its binding to IGF2 mRNA of IGF2 thereby leading to diabetes mellitus [ xref , xref ].|In addition, phosphorylation of IGF2BP2 in the linker region between RRM2 and KH1 by mTOR promotes its binding to the IGF leader 3 mRNA 5\u2032-UTR, enhancing the initiation of IGF2 translation through eIF-4E- and 5\u2032 cap-independent internal ribosomal entry [ xref ].

SIGNOR-280046

O43561

Q9H093

0

phosphorylation

down-regulates activity

0.2

Analysis by an in vitro kinase assay revealed that NUAK2 could phosphorylate immunoprecipitated LATS and that this phosphorylation was lost in the LATS double mutant (DM), T246A/S613A (Fig.\u00a0 xref ).|We showed that phosphorylation of Ser613, located upstream of the KD, adjacent to the MOB binding site and to a lesser extent the N-terminal localized T246, are required for NUAK2 to inhibit LATS.

SIGNOR-280052

P23975

Q13153

0

phosphorylation

down-regulates activity

0.2

PAK1 negatively regulates the activity of the Rho exchange factor NET1.|Specifically, PAK1 phosphorylates NET1 on three sites in vitro : serines 152, 153, and 538.

SIGNOR-280054

P17676

O96013

0

phosphorylation

up-regulates activity

0.2

Importantly, we found that PAK4 enhanced CEBPB phosphorylation on Thr 235.|In summary, we showed that PAK4 mediated CEBPB activation upregulated CLDN4 expression to promote breast cancer cell migration and invasion.

SIGNOR-280055

Q13501

Q9UK99

0

binding

down-regulates quantity by destabilization

0.2

F-box protein Fbxo3 targets Smurf1 ubiquitin ligase for ubiquitination and degradation. Here we show that another F-box protein Fbxo3, belonging to the FBXO type protein family, also interacts with and targets Smurf1 for poly-ubiquitination and proteasomal degradation. The SCF complex is composed of F-box protein, Skp1, Cullin1 (Cul1) and ROC1. Fbxo3, whose substrates are few, forms SCF Fbxo3 ubiquitin ligase and regulates the degradations of Fbxl2, p62, HIPK2 and p300 through the ubiquitin-proteasome pathway.

SIGNOR-272444

Q9UBK2

P49760

0

phosphorylation

down-regulates activity

0.2

Clk2 could also repress PGC-1alpha activation of Foxo1 on the IRS response element , as well as repress the Pepck promoter .|Clk2 phosphorylates and represses PGC-1\u03b1.

SIGNOR-278228

Q9NS28

P17612

0

phosphorylation

up-regulates activity

0.2

Cyclic AMP- and cyclic GMP-dependent kinases (PKA, PKG) inhibit the interaction of RGS18 and 14-3-3 by phosphorylating S216.

SIGNOR-273786

O43426

Q9P286

0

phosphorylation

up-regulates activity

0.2

We identified two novel Pak5 substrates, Pacsin1 and Synaptojanin1, proteins that directly interact with one another to regulate synaptic vesicle endocytosis and recycling. Pacsin1 and Synaptojanin1 were phosphorylated by Pak5 and the other group II Paks in vitro, and Pak5 phosphorylation promoted Pacsin1-Synaptojanin1 binding both in vitro and in vivo.

SIGNOR-263026

Q2M3R5

Q8IXL6

0

phosphorylation

up-regulates activity

0.2

Notably, phosphorylation of Stim1 by Fam20C enhances Stim1 activation and store-operated Ca 2+ entry.|We feel that the western blot shows an appropriate range of contrast to support the conclusion that Stim1 can be activated by Fam20C under high calcium conditions.

SIGNOR-280012

Q9H300

Q15119

0

phosphorylation

up-regulates activity

0.2

As expected, knocking down PDK2 in HEK293 cells that overexpress PARL resulted in a significant increase in beta cleavage in comparison to the control cells.|Furthermore, we show that PDK2, a key regulator in metabolic plasticity, phosphorylates PARL and regulates \u03b2 cleavage.

SIGNOR-280018

P30281

Q15759

0

phosphorylation

down-regulates quantity by destabilization

0.2

P38SAPK2 phosphorylates cyclin D3 at Thr-283 and targets it for proteasomal degradation.

SIGNOR-280023