GleghornLab/Signor_2class · Datasets at Hugging Face

IdA string	IdB string	labels int64	mechanism string	effect string	score float64	sentence string	signor_id string
Q15569	Q9Y281	1	phosphorylation	down-regulates activity	0.321	Like TESK1, TESK2 phosphorylated cofilin specifically at Ser-3 and induced formation of actin stress fibers and focal adhesionsExpression of cofilin or S3A-cofilin into HeLa cells induced marked decreases in rhodamine-phalloidin staining due to the actin binding and -depolymerizing activity of cofilin	SIGNOR-246719
Q8ND76	P06493	0	phosphorylation	down-regulates activity	0.595	Therefore, CDK1 may trigger CFP1 degradation through some indirect mechanisms rather than CFP1 phosphorylation.\|This result suggests that, although CDK1 triggers both phosphorylation and degradation of CFP1 protein, phosphorylation of CFP1 by CDK1 is not a prerequisite for its degradation during cell division.	SIGNOR-279012
Q9UK17	P06241	0	phosphorylation	up-regulates activity	0.2	These results indicate that Y108 (for Src-family kinases) and Y136 (for EGFR kinase) are involved in the tyrosine phosphorylation of hKv4.3 channels.	SIGNOR-276396
P38398	P42685	0	phosphorylation	up-regulates quantity by stabilization	0.2	Herein, we demonstrate that Fyn-related kinase (Frk)/Rak plays an important role in maintaining genomic stability, possibly in part through positively regulating BRCA1 protein stability and function via tyrosine phosphorylation on BRCA1 Tyr1552. Rak-mediated tyrosine phosphorylation of BRCA1 is essential for its stability and function	SIGNOR-275454
Q13188	P17252	1	phosphorylation	up-regulates activity	0.2	Thus, the phosphorylation of PKCα at Ser226 and Thr228 by Mst1 and Mst2 is required for the optimal activation of PKCα.	SIGNOR-277176
P05412	Q99986	0	phosphorylation	up-regulates	0.512	Vrk1 phosphorylates c-jun in ser63 and ser73 in vitro...VRK1 Activates c-jun dependent transcription	SIGNOR-127073
P06241	O75962	1	phosphorylation	up-regulates activity	0.2	Here, we demonstrate that Trio is phosphorylated by Src family kinases in the embryonic rat cortex in response to netrin-1. In vitro, Trio was predominantly phosphorylated at Tyr(2622) by the Src kinase Fyn.	SIGNOR-273855
P19484	Q00534	0	phosphorylation	up-regulates activity	0.2	CDK4 and CDK6 phosphorylate TFEB and TFE3.	SIGNOR-279454
Q05655	Q09472	1	phosphorylation	down-regulates	0.366	Inhibition of histone acetyltransferase function of p300 by pkcdeltawe found that pkcdelta but not classical pkc, specifically phosphorylates p300 at serine 89 in vitro and in vivo. This phosphorylation causes inhibition of p300 intrinsic hat activity.	SIGNOR-94263
Q9UBB4	P53350	0	phosphorylation	down-regulates	0.353	Phosphorylation of ataxin-10 by polo-like kinase 1 is required for cytokinesis. Plk1 phosphorylates ataxin-10 at s77 and t82 in vitro. we found that ataxin-10 is ubiquitinated, and is subject to proteasome-dependent degradation, which is delayed in the 2a mutant. We propose a model in which plk1 phosphorylation of ataxin-10 influences its degradation and cytokinesis	SIGNOR-176122
P07947	Q04760	1	phosphorylation	up-regulates activity	0.2	We show that Glo1 activity is promoted by phosphorylation on Tyrosine 136 via multiple kinases. Glo1 Y136 is phosphorylated by multiple different kinases including all members of the Src family. Depletion of multiple different kinases led to a partial reduction in Glo1(Y136) phosphorylation. These included members of the Src family (Src, Yes1, FGR, and the related Abl1), and of the FAK, EPHA, FGFR, and VEGFR families (Figure 2B), suggesting phosphorylation of Glo1 on Y136 by multiple different kinases. In vitro kinase assays revealed that all the members of the Src family, as well as Epha5 and VEGFR3, can efficiently phosphorylate recombinant Glo1 on Y136 (Figure 2C–D).	SIGNOR-276185
Q9NZV8	P42658	0	relocalization	up-regulates activity	0.548	DPPX-S reduced energy barriers of the voltage-dependent transitions; therefore, this auxiliary subunit may exert a catalytic effect on voltage-dependent gating of Kv4.2 channels. DPPX-S may also accelerate coupled inactivation indirectly	SIGNOR-269005
Q15831	P38936	1	phosphorylation	down-regulates activity	0.488	Mass spectrometry analysis of the phosphorylated CDKN1A identified Thr80 as the residue phosphorylated by LKB1 in vitro (Figure 4A and S5A).\|UVB induced phosphorylation of LKB1 T366 mediates CDKN1A degradation.	SIGNOR-278253
P09211	Q02156	0	phosphorylation	up-regulates activity	0.2	Peptide phosphorylation analyses and both phosphorylation and enzyme kinetic studies with GSTP1 proteins mutated at candidate amino acid residues established Ser-42 and Ser-184 as putative phospho-acceptor residues for both kinases in the GSTP1 protein. Together, these findings show PKA- and PKC-dependent phosphorylation as a significant post-translational mechanism of regulation of GSTP1 function. Together, these results further support S42 and S184 as major phosphor-acceptor residues for PKA and PKC and suggest that the increased activity of the phospho-GSTP1 was not simply a consequence of the negative charge introduced in the GSTP1 protein by the phosphate group.All eight PKC isoforms, PKC-α, PKC-βI, PKC-βII, PKC-ε, PKC-γ, PKC-η, and PKC-ζ phosphorylated the GSTP1 protein efficiently	SIGNOR-276021
Q13535	Q99708	1	phosphorylation	up-regulates	0.615	Characterization of this site using phospho-specific antibodies and mutational analysis reveals that it is phosphorylated by atr and is required for binding of ctip to chromatin and subsequent processive resection.	SIGNOR-200245
P68400	P04637	1	phosphorylation	up-regulates activity	0.668	Furthermore, we demonstrate that anisomycin- and tumor necrosis factor-alpha-induced phosphorylation of p53 at Ser-392, which is important for the transcriptional activity of this growth suppressor protein, requires p38 MAP kinase and CK2 activities.	SIGNOR-250967
Q7L804	Q7KZI7	0	phosphorylation	up-regulates	0.42	We identified the kinase that phosphorylated rab11-fip2 as mark2/emk1/par-1balpha (mark2), and recombinant mark2 phosphorylated rab11-fip2 only on serine 227. In calcium switch assays, cells expressing rab11-fip2(s227a) showed a defect in the timely reestablishment of p120-containing junctional complexes.	SIGNOR-147118
O96013	P18084	1	phosphorylation	up-regulates	0.451	Pak4 specifically phosphorylated the integrin beta5 subunit at ser-759 and ser-762 within the beta5-sers-motif. Point mutation of these two serine residues abolished the pak4-induced cell migration, indicating a functional role for these phosphorylations in migration.	SIGNOR-165702
Q92985	P03209	0	transcriptional regulation	down-regulates quantity by repression	0.2	EBV Rta selectively down-regulates the expression of IRF3 and IRF7, the main regulators of the Type I IFNs.	SIGNOR-266645
P53350	P40763	0	transcriptional regulation	up-regulates quantity by expression	0.306	Stat3 directly activated transcription of PLK1 in esophageal cancer cells and mouse embryonic fibroblast cell NIH3T3.	SIGNOR-271690
P00519	P17676	1	phosphorylation	up-regulates	0.399	The y79 amino acid residue of c/ebpbeta was phosphorylated by c-abl or arg. The phosphorylation of c/ebpbeta resulted in an increased c/ebpbeta stability and a potentiation of c/ebpbeta transcription activation activity in cells	SIGNOR-186423
P24941	Q96PX1	1	phosphorylation	up-regulates activity	0.287	CDK2 promotes phosphorylation of RNF157 at the same Ser 660-663 residues that become phosphorylated downstream of combined PI3K and MAPK pathway activity.	SIGNOR-279016
Q9H2X9	Q9BYP7	0	phosphorylation	down-regulates activity	0.46	We have shown that with-no-lysine kinase 3 (WNK3) possesses several properties that suggest it could be the Cl−/volume-sensitive regulatory kinase that, in association with protein phosphatases, reciprocally modifies the phosphorylation/dephosphorylation states of the SLC12 proteins and thus their activities\|WNK3 activates NKCC1/2 and NCC and inhibits the KCCs	SIGNOR-264628
P42345	P51397	1	phosphorylation	down-regulates activity	0.395	A critical step in autophagy induction comprises the inactivation of a key negative regulator of the process, the Ser/Thr kinase mammalian target of rapamycin (mTOR). Here we identify death-associated protein 1 (DAP1) as a novel substrate of mTOR that negatively regulates autophagy. Mapping of the phosphorylation sites and analysis of phosphorylation mutants indicated that DAP1 is functionally silenced in growing cells through mTOR-dependent phosphorylations on Ser3 and Ser51.	SIGNOR-259812
Q13535	Q8IUH4	1	phosphorylation	up-regulates activity	0.2	Collectively these results suggest that ZDHHC13 phosphorylation by ATR following UVB irradiation promotes its interaction with MC1R to stimulate MC1R palmitoylation.	SIGNOR-273517
P42229	P36888	0	phosphorylation	up-regulates activity	0.605	FLT3-ITDs induced a strong activation of STAT5. FLT3-ITD mutants induce an autophosphorylation of the receptor, interleukin 3-independent growth in Ba/F3 cells, and a strong STAT5 and mitogen-activated protein kinase (MAPK) activation.	SIGNOR-261516
P06493	Q92574	1	phosphorylation	down-regulates	0.489	Cell cycle-regulated phosphorylation of hamartin, the product of the tuberous sclerosis complex 1 gene, by cyclin-dependent kinase 1/cyclin b.Cyclin-dependent kinase 1 phosphorylates hamartin at three sites, one of which (thr417) is in the hamartin-tuberin interaction domain. Tuberin interacts with phosphohamartin, and tuberin expression attenuates the phosphorylation of exogenous hamartin. Hamartin with alanine mutations in the three cyclin-dependent kinase 1 phosphorylation sites increased the inhibition of p70s6 kinase by the hamartin-tuberin complex	SIGNOR-118584
Q12809	P17612	0	phosphorylation	up-regulates	0.307	Deletion of protein kinase a phosphorylation sites in the herg potassium channel inhibits activation shift by protein kinase afour consensus pka phosphorylation sites (s283a, s890a, t895a, s1137a)	SIGNOR-70726
P18031	P29320	1	dephosphorylation	down-regulates activity	0.417	Nevertheless, the finding that phosphorylation of the activation loop tyrosine (EphA3-Y779), a recently identified PTP1B substrate (Mertins et al., 2008), is essential for ligand-induced endocytosis (Janes et al., 2009)	SIGNOR-248426
Q13233	Q92918	0	phosphorylation	up-regulates	0.455	Hpk1 binds and phosphorylates mekk1 directly,	SIGNOR-43996
P05771	P04049	1	phosphorylation	up-regulates	0.445	Pkc can effectively phosphorylate raf-1, this is a direct effect of activated pkc and not the result of raf-1 autophosphorylation. the sites of pkc-mediated raf-1 phosphorylation are deduced to be ser497 and ser619.	SIGNOR-37474
O00401	Q07912	0	phosphorylation	up-regulates activity	0.307	Because TNK2 phosphorylation of WASL increases its actin nucleation activity ( xref ), we reasoned that it might be possible to complement the TNK2 deficiency by overexpression of WASL.\|For NCK1, based on its reported binding to WASL and TNK2, we hypothesized that its function is to recruit WASL to TNK2, which could then activate WASL via phosphorylation ( xref ; xref ).	SIGNOR-280155
Q13107	O43395	1	deubiquitination	down-regulates activity	0.487	Prp3 is deubiquitinated by Usp4 and its substrate targeting factor, the U4/U6 recycling protein Sart3, which likely facilitates ejection of U4 proteins from the spliceosome during maturation of its active site.	SIGNOR-271975
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
Q13164	Q15256	0	dephosphorylation	down-regulates activity	0.45	In this study we concentrated on whether and how PTP-SL, a kinase-interacting motif-containing PTP, might be involved in the down-regulation of the ERK5 signal\|Whereas inactivation of ERK5 by PTP-SL monitored in vitro is most probably simply due to the dephosphorylation of tyrosine 220 in the activating TEY motif	SIGNOR-248721
Q13233	P40763	1	phosphorylation	up-regulates activity	0.291	Phosphorylation of s727 induces pin1 binding which increases transcription. Pin1 binding increases stat3 interaction with p300 and dna.	SIGNOR-236346
Q96L34	Q15831	0	phosphorylation	up-regulates	0.535	Lkb1 is a master kinase that activates 13 kinases of the ampk subfamily, including mark/par-1we recently demonstrated that the lkb1 tumour suppressor kinase, in complex with the pseudokinase strad and the scaffolding protein mo25, phosphorylates and activates amp-activated protein kinase (ampk). A total of 12 human kinases (nuak1, nuak2, brsk1, brsk2, qik, qsk, sik, mark1, mark2, mark3, mark4 and melk) are related to ampk. Here we demonstrate that lkb1 can phosphorylate the t-loop of all the members of this subfamily, apart from melk, increasing their activity >50-fold	SIGNOR-122682
P02545	P55212	0	cleavage	down-regulates	0.662	Lamin a breakdown is largely mediated by caspase-6 during the execution phase of apoptosis.	SIGNOR-83611
P29122	P04275	1	cleavage	up-regulates activity	0.293	Like PACE,PACE4 was able to process pro-vWF to its mature form, and efficient cleavage required both the P4 arginine and the P2 lysine	SIGNOR-260367
O95425	P53350	0	phosphorylation	up-regulates activity	0.2	PLK1 phosphorylates Ser238 of SVIL, which can promote the localization of SVIL to the central spindle and association with PRC1. Expression of a PLK1 phosphorylation site mutant, S238A-SVIL, inhibited myosin II activation at the equatorial cortex and induced aberrant furrowing.	SIGNOR-273729
Q12778	Q96J02	0	ubiquitination	down-regulates quantity by destabilization	0.258	Mechanistically, Itch ubiquitinates Foxo1 for proteasomal degradation.	SIGNOR-278698
P31749	Q969V5	0	ubiquitination	down-regulates quantity by destabilization	0.475	The results of the functional studies suggest that the degradation of Akt by MULAN suppresses cell proliferation and viability.	SIGNOR-252437
O43524	Q9Y243	0	phosphorylation	down-regulates quantity by destabilization	0.708	AKT phosphorylates FOXO3a at three conserved sites (Thr32, Ser253 and Ser315), therefore creating binding sites for the 14-3-3 chaperone proteins and leading to the active export of FOXO3a to the cytoplasm where it is targeted for proteasomal degradation.	SIGNOR-249644
Q01543	Q9UPS8	1	transcriptional regulation	down-regulates quantity by repression	0.284	In healthy individual, RUNX1/FLI1 complex negatively regulates ANKRD26 gene expression in MKs.	SIGNOR-266070
Q9H257	Q9BVG3	0	ubiquitination	up-regulates activity	0.51	Importantly, using in vitro ubiquitination assays with purified proteins, we verified that CARD9 is directly ubiquitinated by TRIM62 at residue K125; this ubiquitination is dependent on the ligase activity of TRIM62 and does not occur in CARD9 Delta11 (XREF_FIG).	SIGNOR-278552
Q05516	P49841	0	phosphorylation	up-regulates activity	0.2	Taken together, we conclude that S184 and T282 of ZBTB16 may be phosphorylated by GSK3beta in cells under serum starvation condition.	SIGNOR-279618
Q9HC16	P17612	0	phosphorylation	up-regulates	0.324	Here we show that pka binds and specifically phosphorylates a3g at thr32 in vitro and in vivo. This phosphorylation event reduces the binding of a3g to vif and its subsequent ubiquitination and degradation, and thus promotes a3g antiviral activity.	SIGNOR-181526
Q9UNE7	Q86WG3	1	polyubiquitination	down-regulates quantity by destabilization	0.378	CHIP e.g. was found to efficiently polyubiquitinate caytaxin in vitro, suggesting that it might influence caytaxin degradation in vivo.	SIGNOR-272651
P04798	P35869	0	transcriptional regulation	up-regulates quantity by expression	0.684	Kaempferol proved to be capable of inhibiting binding of agonist and agonist-induced formation of the AHR/ARNT DNA-binding complex and upregulation of the AHR target gene, CYP1A1.	SIGNOR-259909
P18850	Q16549	0	phosphorylation	up-regulates	0.2	We discovered that azc, an agent that causes the formation of abnormal proteins, stimulates the stress-activated kinase p38 mapk, which phosphorylates atf6	SIGNOR-89813
Q13043	Q9H8S9	1	phosphorylation	up-regulates	0.9	Mob1, when phosphorylated by MST1/2, binds to the autoinhibitory motif in Lats1/2, which in turn leads to the phosphorylation of the Lats activation loop (Lats1 S909 and Lats2 S872) and thereby an increase of their kinase activity	SIGNOR-201306
P63000	Q96N67	0	guanine nucleotide exchange factor	up-regulates activity	0.545	As a GEF, Dock7 exchanges GDP for GTP on Cdc42 and Rac1, causing their activation, followed by activation of downstream effectors, including the dephosphorylation (activation) of cofilin, a key regulator of actin turnover.	SIGNOR-261887
P10415	Q5S007	0	phosphorylation	up-regulates activity	0.329	Thus, we propose that Thr56 phosphorylation of Bcl-2 by LRRK2 G2019S might be a crucial step of mitochondrial disorder, which initiates the subsequent cellular damage in the context of PD relevant to G2019S.\|We found that LRRK2 G2019S induced loss of the MMP was recovered in both GFP-Bcl-2 and GFP-M-Bcl-2 stable cells (XREF_FIG -lower panel).	SIGNOR-279531
Q13950	P06493	0	phosphorylation	up-regulates	0.479	In vitro kinase assays using recombinant cdc2 kinase showed that runx2 was phosphorylated at ser(451) the cdc2 inhibitor roscovitine dose dependently inhibited in vivo runx2 dna-binding activity during mitosis and the runx2 mutant s451a exhibited lower dna-binding activity and reduced stimulation of anchorage-independent growth relative to wild type runx2.	SIGNOR-143586
O14974	O75116	0	phosphorylation	down-regulates activity	0.785	Rho kinase is known to control smooth muscle contractility by phosphorylating the 110 kDa myosin-targetting subunit (MYPT1) of the myosin-associated form of protein phosphatase 1 (PP1M). Phosphorylation of MYPT1 at Thr695 has previously been reported to inhibit the catalytic activity of PP1. Here, we show that the phosphorylation of Thr850 by Rho kinase dissociates PP1M from myosin, providing a second mechanism by which myosin phosphatase activity is inhibited.	SIGNOR-249164
O14672	P46531	1	cleavage	up-regulates activity	0.782	ADAM10-mediated Notch1 cleavage is the rate limiting-step for release of the NICD and subsequent activation of Notch1 signaling. In T cells ADAM10-mediated Notch1 shedding controls T cell development	SIGNOR-259838
Q13315	Q13541	1	phosphorylation	down-regulates	0.512	Here we report that atm... phosphorylates 4e-bp1 at ser 111cells lacking atm kinase activity exhibit a significant decrease in the insulin-induced dissociation of 4e-bp1 from eif-4e.	SIGNOR-85619
P24844	Q05397	0	phosphorylation	up-regulates activity	0.286	It indicates that FAK positively regulates the phosphorylation of MLC2.	SIGNOR-280098
Q13144	P19784	0	phosphorylation	up-regulates activity	0.37	Two conserved sites (Ser712/713) are phosphorylated by casein kinase 2. They lie at the extreme C-terminus and are required for the interaction of eIF2Bepsilon with its substrate, eIF2, in vivo and for eIF2B activity in vitro.	SIGNOR-250990
P40426	P55075	1	transcriptional regulation	down-regulates quantity by repression	0.2	Our results in ES cells suggest that Engrailed inhibits Fgf8 expression in the absence of Pbx1. We identified single Engrailed- and Pbx-binding sites in the Fgf8 intron that inhibit expression of Fgf8 in mouse ES cells, but that together can allow full Fgf8 expression. Our data support the model that Engrailed heterodimerized with Pbx might activate transcription, while Engrailed or Pbx proteins alone might repress transcription	SIGNOR-265779
O14672	P16070	1	cleavage	up-regulates activity	0.346	The ADAM proteases are best known for their role in shedding the extracellular domain of transmembrane proteins. Among the transmembrane proteins shed by ADAM10 are notch, HER2, E-cadherin, CD44, L1 and the EGFR ligands, EGF and betacellulin.	SIGNOR-259847
O60260	Q13501	1	ubiquitination	down-regulates quantity by destabilization	0.2	Once activated, parkin interacts with and subsequently ubiquitinates p62 at the K13 residue, resulting in the degradation of p62 via the proteasomal dependent pathway.	SIGNOR-278524
P10636	Q7KZI7	0	phosphorylation	down-regulates activity	0.707	We have studied the relationship between the phosphorylation oftau by several kinases (MARK, PKA, MAPK, GSK3) and its assembly into PHFs. By contrast, MARK and PKA phosphorylate several sites within the repeats (notably theKXGS motifs including Ser262, Ser324, and Ser356, plus Ser320); in addition PKA phosphorylates somesites in the flanking domains, notably Ser214. This type of phosphorylation strongly reduces tau’s affinityfor microtubules, and at the same time inhibits tau’s assembly into PHFs.	SIGNOR-275436
Q00535	O14490	1	phosphorylation	down-regulates quantity by destabilization	0.408	Taken together, these sets of data suggest that Abeta triggers the phosphorylation of GKAP by cdk5 at the serine residues S77 and S111 that in turn are crucial for GKAP degradation.	SIGNOR-279153
P06493	Q8WVD3	1	phosphorylation	up-regulates activity	0.2	Altogether, our results suggest RNF138 is phosphorylated at position T27 in a CDK1- and CDK2-dependent manner.Altogether, our results suggest RNF138 is phosphorylated at position T27 in a CDK1- and CDK2-dependent manner.	SIGNOR-277832
P48730	P11308	1	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
P12036	P28482	0	phosphorylation	up-regulates activity	0.368	The fraction containing Erk2, as well as bacterially expressed Erk1 and Erk2, phosphorylated all types of KSP motifs in peptides (KSPXK, KSPXXK, KSPXXXK, and KSPXXXXK) derived from NF-M and NF-H. They also phosphorylated an expressed 24 KSPXXXK repeat NF-H polypeptide, an expressed NF-H as well as dephosphorylated native rat NF-H, and NF-M proteins with accompanying decreases in their respective electrophoretic mobilities. \|Our data on primary hippocampal cells also showed an inhibition of neurite outgrowth by the drug that was accompanied by inhibition of MAP, NF-H, and NF-M phosphorylation.	SIGNOR-249424
O43561	P45983	0	phosphorylation	down-regulates	0.308	Lat, an adapter protein essential for t-cell signaling, is phosphorylated at its thr 155 by erk in response to t-cell receptor stimulation. Thr 155 phosphorylation reduces the ability of lat to recruit plcgamma1 and slp76, leading to attenuation of subsequent downstream events such as [ca2+]i mobilization and activation of the erk pathway.Mutational analysis revealed that t155 but not t94 or t140 is the site of jnk-mediated phosphorylation (figure 2b). Erk also phosphorylated lat at t155 (figure 2c), whereas p38, which was able to phosphorylate atf2, failed to induce threonine phosphorylation of lat (figure 2d). These results indicate that lat is directly phosphorylated by erk and jnk at the same site, t155.	SIGNOR-125774
Q02763	P35590	1	phosphorylation	up-regulates activity	0.348	Thus, Tie2 was able to induce Tie1 phosphorylation.\|When cotransfected, Tie2 formed heteromeric complexes with Tie1, enhanced Tie1 activation, and induced phosphorylation of a kinase-inactive Tie1 in a ligand-dependent manner.	SIGNOR-279769
Q04759	P35568	1	phosphorylation	down-regulates activity	0.567	Protein kinase C Theta inhibits insulin signaling by phosphorylating IRS1 at Ser(1101).	SIGNOR-260906
P12931	Q01973	0	phosphorylation	up-regulates	0.318	Ror1 binds to and phosphorylates c-src / ror1 kinase-dependent c-src activation	SIGNOR-196751
Q13571	P46934	0	ubiquitination	up-regulates activity	0.476	These results suggest that LAPTM5 ubiquitination is mediated by Nedd4.\|Thus, Nedd4 promotes the recruitment of GGA3 to LAPTM5, allowing LAPTM5 translocation from the Golgi to the lysosome with the aid of GGA3.	SIGNOR-278768
P36894	Q9HAU4	0	ubiquitination	down-regulates	0.552	Smurf1 and smurf2 are e3 ubiquitin ligases known to suppress tgf-beta signaling through degra-dation of smads and receptors for tgf-beta and bmps	SIGNOR-192898
O43248	P04271	1	transcriptional regulation	up-regulates quantity by expression	0.252	HOXC6 and HOXC11 increase transcription of S100beta gene in BrdU-induced in vitro differentiation of GOTO neuroblastoma cells into Schwannian cells.	SIGNOR-261647
P06493	O00399	1	phosphorylation	up-regulates activity	0.307	Here, we show that the p27/p25 heterodimer undergoes mitotic phosphorylation by cyclin‐dependent kinase 1 (Cdk1) at a single site, p27 Thr186, to generate an anchoring site for polo‐like kinase 1 (Plk1) at kinetochores.	SIGNOR-264777
Q96EB6	Q9Y618	1	null	up-regulates	0.494	In differentiated adipocyte cell lines, SIRT1 inhibits adipogenesis and enhances fat mobilization through lipolysis by suppressing the activity of PPARγ. SIRT1 achieves this by promoting the assembly of a corepressor complex, involving NCoR1 and SMRT, on the promoters of PPARγ target genes to repress their transcription.	SIGNOR-253506
Q8WVD3	P24941	0	phosphorylation	up-regulates activity	0.2	Altogether, our results suggest RNF138 is phosphorylated at position T27 in a CDK1- and CDK2-dependent manner.Altogether, our results suggest RNF138 is phosphorylated at position T27 in a CDK1- and CDK2-dependent manner.	SIGNOR-277831
P61006	Q9Y6E0	0	phosphorylation	up-regulates activity	0.275	In a screen for Rab8A kinases we identify TAK1 and MST3 kinases that can efficiently phosphorylate the Switch II residue Threonine72 (Thr72) in a similar manner as LRRK2 in vitro. \|Overall our data suggests that the phosphorylation of Rab8A at Ser111 may influence Switch II-binding by regulators, thus disrupting interactions with its cognate GEF and moderately impairs its interaction with GAPs.\|The antagonistic interplay between Ser111 phosphorylation and Thr72 phosphorylation is genetically concordant with how respective mutations in PINK1 and LRRK2 cause Parkinson’s disease	SIGNOR-260265
Q16539	P35813	0	dephosphorylation	down-regulates activity	0.408	Moreover, when expressed in mammalian cells, pp2ca inhibited the activation of the p38 and jnk cascades induced by environmental stresses. Both in vivo and in vitro observations indicated that pp2ca dephosphorylated and inactivated mapkks (mkk6 and sek1) and a mapk (p38) in the stress-responsive mapk cascades. Furthermore, a direct interaction of pp2ca and p38 was demonstrated by a co-immunoprecipitation assay	SIGNOR-59618
P15927	Q13315	0	phosphorylation	up-regulates	0.809	Replication protein a (rpa) is a single-stranded dna (ssdna) binding protein involved in various processes, including nucleotide excision repair and dna replication. The 32 kda subunit of rpa (rpa32) is phosphorylated in response to various dna-damaging agents, and two protein kinases, ataxia-telangiectasia mutated (atm) and the dna-dependent protein kinase (dna-pk) have been implicated in dna damage-induced phosphorylation of rpa32we show that both dna-pk and atm phosphorylate rpa32 on thr21 in vitro.	SIGNOR-121861
Q12979	P63000	1	gtpase-activating protein	down-regulates activity	0.504	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-260525
Q15418	P67809	1	phosphorylation	up-regulates	0.543	We therefore conclude that rsk1/rsk2 are novel activators of yb-1, able to phosphorylate the serine 102 residue.	SIGNOR-182497
P68400	Q01534	1	phosphorylation	up-regulates activity	0.2	CK2-dependent C-terminal phosphorylation at T300 directs the nuclear transport of TSPY protein	SIGNOR-250969
P68400	P55087	1	phosphorylation	down-regulates activity	0.416	We found that the stress-induced kinase casein kinase (CK)II phosphorylates the Ser276 immediately preceding the tyrosine motif, increasing AQP4-mu 3A interaction and enhancing AQP4-lysosomal targeting and degradation. AQP4 phosphorylation by CKII may thus provide a mechanism that regulates AQP4 cell surface expression. \| To determine whether Ser276 is an actual CKII substrate, we used GST–AQP4-Cter proteins in which only one out of the three C-terminal CKII consensus sites was sequentially conserved (Ser276, Ser285 and Ser315, respectively). Figure 7B (right panel) shows that the three serine residues, including Ser276, were indeed efficiently phosphorylated by CKII.	SIGNOR-250827
P12931	P60174	1	phosphorylation	up-regulates quantity by stabilization	0.2	As shown in xref , Tim was phosphorylated by both Hck and c-Src, and to a lesser extent by Fyn and c-Yes.\|In the case of Hck and Fyn, co-expression led to enhanced Tim turnover, while c-Src and c-Yes promoted Tim stability.	SIGNOR-280136
P00441	O96017	0	phosphorylation	up-regulates activity	0.376	ROS signaling is mediated by Mec1/ATM and its effector Dun1/Cds1 kinase, through Dun1 interaction with Sod1 and regulation of Sod1 by phosphorylation at S60, 99. In the nucleus, Sod1 binds to the promoters and regulates the expression of oxidative resistance and repair genes.	SIGNOR-262794
P12931	P50402	1	phosphorylation	down-regulates	0.451	Src phosphorylated emerin specifically at y59, y74 and y95; interestingly y-to-f substitutions at identified src sites reduced recombinant emerin binding to endogenous baf	SIGNOR-188308
Q15691	P48730	0	phosphorylation	up-regulates activity	0.505	We further show that casein kinase 1\u03b4 binds and phosphorylates EB1 and promotes microtubule growth.	SIGNOR-279165
P19525	P52564	1	phosphorylation	up-regulates activity	0.2	Consistent with this observation, PKR was capable of activating MKK6 as assessed in a coupled kinase assay containing the components of the p38 MAPK pathway.\|In vitro kinase assays revealed that MKK6 was efficiently phosphorylated by PKR, and this could be inhibited by 2-aminopurine.	SIGNOR-279707
Q13131	P46527	1	phosphorylation	up-regulates quantity by stabilization	0.267	P27Kip1-Mediated Cell Survival Is Dependent on AMPK-Specific Thr198 Phosphorylation\|AMPK-dependent phosphorylation of p27Kip1 on Thr198 promotes p27Kip1 protein stability, resulting in more autophagy and less apoptosis.	SIGNOR-259859
Q9BWW4	P06239	0	phosphorylation	up-regulates activity	0.2	The Src tyrosine kinase inhibitor PP2 blocked the nuclear translocation of Ssdp1. Western blot analysis showed that co-expression of Ssdp1 and Lck in 293T cells induces Ssdp1 phosphorylation. Mutation of the Ssdp1 N terminal tyrosine residues 23 and 25 markedly reduced both the phosphorylation and the nuclear localization of Ssdp1. Lck enhanced the transcriptional activity of Ssdp1 in the context of known components of a LIM-homeodomain (LIM-HD)/cofactor complex.	SIGNOR-273648
P10275	P12931	0	phosphorylation	up-regulates activity	0.76	In addition to the ability of Src to promotes castration resistant progression and AR activation, Src is involved in regulating prostate cancer cell migration, invasion, and metastasis and affects bone remodeling.\|These data suggest that downstream of cell surface receptors, Ack1 mediates AR tyrosine phosphorylation at Tyr 267 and Src mediates AR tyrosine phosphorylation at Tyr 534.	SIGNOR-278168
P22681	O00459	1	ubiquitination	down-regulates	0.606	Cbl-b, a ring-type e3 ubiquitin protein ligase, is implicated in setting the threshold of t lymphocyte activation. The p85 regulatory subunit of phosphatidylinositol 3 kinase (pi3k) was identified as a substrate for cbl-b. We have shown that cbl-b negatively regulated p85 in a proteolysis-independent manner.	SIGNOR-110063
P17612	P35367	1	phosphorylation	down-regulates	0.2	Two amino acid residues (ser396, ser398) on hr1 were determined to be pkc phosphorylation sites by in vitro phosphorylation studies.Site-directed mutagenesis studies suggests that the ser398 residue was primarily involved in pkc-mediated desensitization. Possibly, phosphorylation of the residues is required for receptor transport from endosomes to lysosomes.	SIGNOR-128411
Q9UHD2	P08631	0	phosphorylation	down-regulates activity	0.2	The Src family kinases (SFKs) Lck, Hck, and Fgr directly phosphorylate TBK1 at Tyr354/394, to prevent TBK1 dimerization and activation.	SIGNOR-276727
Q9NR97	Q9NWF9	0	polyubiquitination	down-regulates quantity by destabilization	0.257	E3 ligase RNF216 (ring finger protein 216) targets TLR8 for ubiquitination and degradation.	SIGNOR-272257
P00519	O15269	1	phosphorylation	down-regulates	0.2	We demonstrated that the er-resident human protein serine palmitoyltransferase long chain-1 (sptlc1), which is the first enzyme of sphingolipid biosynthesis, is phosphorylated at tyr(164) by the tyrosine kinase abl. this occurred through the specific abl-mediated phosphorylation of sptlc1 on tyr164, leading to the attenuation of its activity.	SIGNOR-202003
P04637	Q6PCD5	0	ubiquitination	up-regulates quantity by stabilization	0.361	RFWD3 is a positive regulator of p53 abundance and regulates the G1 checkpoint in response to IR. We found that an E3 ubiquitin ligase RFWD3 (RNF201/FLJ10520) forms a complex with Mdm2 and p53 to synergistically ubiquitinate p53 and is required to stabilize p53 in the late response to DNA damage.	SIGNOR-271944
Q96AC1	Q8IWT3	0	ubiquitination	down-regulates quantity by destabilization	0.2	M-phase-specific CDK1–cyclin B1 complex directly binds KIND1 and KIND2 and phosphorylates a conserved proline-directed CDK1 consensus motif in the flexible and intrinsically disordered loop of the F1 domain. This then results in the recruitment of the CUL9–FBXL10 complex, modification with K48-linked polyubiquitin chains and proteasomal degradation of KIND1 and KIND2.	SIGNOR-276717
Q96PY6	Q9UKI8	0	phosphorylation	up-regulates activity	0.29	TLK1 phosphorylated NEK1 at T141, which lies in the kinase domain, and caused an increase in its activity.	SIGNOR-275840

Q15569

Q9Y281

1

phosphorylation

down-regulates activity

0.321

Like TESK1, TESK2 phosphorylated cofilin specifically at Ser-3 and induced formation of actin stress fibers and focal adhesionsExpression of cofilin or S3A-cofilin into HeLa cells induced marked decreases in rhodamine-phalloidin staining due to the actin binding and -depolymerizing activity of cofilin

SIGNOR-246719

Q8ND76

P06493

0

phosphorylation

down-regulates activity

0.595

Therefore, CDK1 may trigger CFP1 degradation through some indirect mechanisms rather than CFP1 phosphorylation.|This result suggests that, although CDK1 triggers both phosphorylation and degradation of CFP1 protein, phosphorylation of CFP1 by CDK1 is not a prerequisite for its degradation during cell division.

SIGNOR-279012

Q9UK17

P06241

0

phosphorylation

up-regulates activity

0.2

These results indicate that Y108 (for Src-family kinases) and Y136 (for EGFR kinase) are involved in the tyrosine phosphorylation of hKv4.3 channels.

SIGNOR-276396

P38398

P42685

0

phosphorylation

up-regulates quantity by stabilization

0.2

Herein, we demonstrate that Fyn-related kinase (Frk)/Rak plays an important role in maintaining genomic stability, possibly in part through positively regulating BRCA1 protein stability and function via tyrosine phosphorylation on BRCA1 Tyr1552. Rak-mediated tyrosine phosphorylation of BRCA1 is essential for its stability and function

SIGNOR-275454

Q13188

P17252

1

phosphorylation

up-regulates activity

0.2

Thus, the phosphorylation of PKCα at Ser226 and Thr228 by Mst1 and Mst2 is required for the optimal activation of PKCα.

SIGNOR-277176

P05412

Q99986

0

phosphorylation

up-regulates

0.512

Vrk1 phosphorylates c-jun in ser63 and ser73 in vitro...VRK1 Activates c-jun dependent transcription

SIGNOR-127073

P06241

O75962

1

phosphorylation

up-regulates activity

0.2

Here, we demonstrate that Trio is phosphorylated by Src family kinases in the embryonic rat cortex in response to netrin-1. In vitro, Trio was predominantly phosphorylated at Tyr(2622) by the Src kinase Fyn.

SIGNOR-273855

P19484

Q00534

0

phosphorylation

up-regulates activity

0.2

CDK4 and CDK6 phosphorylate TFEB and TFE3.

SIGNOR-279454

Q05655

Q09472

1

phosphorylation

down-regulates

0.366

Inhibition of histone acetyltransferase function of p300 by pkcdeltawe found that pkcdelta but not classical pkc, specifically phosphorylates p300 at serine 89 in vitro and in vivo. This phosphorylation causes inhibition of p300 intrinsic hat activity.

SIGNOR-94263

Q9UBB4

P53350

0

phosphorylation

down-regulates

0.353

Phosphorylation of ataxin-10 by polo-like kinase 1 is required for cytokinesis. Plk1 phosphorylates ataxin-10 at s77 and t82 in vitro. we found that ataxin-10 is ubiquitinated, and is subject to proteasome-dependent degradation, which is delayed in the 2a mutant. We propose a model in which plk1 phosphorylation of ataxin-10 influences its degradation and cytokinesis

SIGNOR-176122

P07947

Q04760

1

phosphorylation

up-regulates activity

0.2

We show that Glo1 activity is promoted by phosphorylation on Tyrosine 136 via multiple kinases. Glo1 Y136 is phosphorylated by multiple different kinases including all members of the Src family. Depletion of multiple different kinases led to a partial reduction in Glo1(Y136) phosphorylation. These included members of the Src family (Src, Yes1, FGR, and the related Abl1), and of the FAK, EPHA, FGFR, and VEGFR families (Figure 2B), suggesting phosphorylation of Glo1 on Y136 by multiple different kinases. In vitro kinase assays revealed that all the members of the Src family, as well as Epha5 and VEGFR3, can efficiently phosphorylate recombinant Glo1 on Y136 (Figure 2C–D).

SIGNOR-276185

Q9NZV8

P42658

0

relocalization

up-regulates activity

0.548

DPPX-S reduced energy barriers of the voltage-dependent transitions; therefore, this auxiliary subunit may exert a catalytic effect on voltage-dependent gating of Kv4.2 channels. DPPX-S may also accelerate coupled inactivation indirectly

SIGNOR-269005

Q15831

P38936

1

phosphorylation

down-regulates activity

0.488

Mass spectrometry analysis of the phosphorylated CDKN1A identified Thr80 as the residue phosphorylated by LKB1 in vitro (Figure 4A and S5A).|UVB induced phosphorylation of LKB1 T366 mediates CDKN1A degradation.

SIGNOR-278253

P09211

Q02156

0

phosphorylation

up-regulates activity

0.2

Peptide phosphorylation analyses and both phosphorylation and enzyme kinetic studies with GSTP1 proteins mutated at candidate amino acid residues established Ser-42 and Ser-184 as putative phospho-acceptor residues for both kinases in the GSTP1 protein. Together, these findings show PKA- and PKC-dependent phosphorylation as a significant post-translational mechanism of regulation of GSTP1 function. Together, these results further support S42 and S184 as major phosphor-acceptor residues for PKA and PKC and suggest that the increased activity of the phospho-GSTP1 was not simply a consequence of the negative charge introduced in the GSTP1 protein by the phosphate group.All eight PKC isoforms, PKC-α, PKC-βI, PKC-βII, PKC-ε, PKC-γ, PKC-η, and PKC-ζ phosphorylated the GSTP1 protein efficiently

SIGNOR-276021

Q13535

Q99708

1

phosphorylation

up-regulates

0.615

Characterization of this site using phospho-specific antibodies and mutational analysis reveals that it is phosphorylated by atr and is required for binding of ctip to chromatin and subsequent processive resection.

SIGNOR-200245

P68400

P04637

1

phosphorylation

up-regulates activity

0.668

Furthermore, we demonstrate that anisomycin- and tumor necrosis factor-alpha-induced phosphorylation of p53 at Ser-392, which is important for the transcriptional activity of this growth suppressor protein, requires p38 MAP kinase and CK2 activities.

SIGNOR-250967

Q7L804

Q7KZI7

0

phosphorylation

up-regulates

0.42

We identified the kinase that phosphorylated rab11-fip2 as mark2/emk1/par-1balpha (mark2), and recombinant mark2 phosphorylated rab11-fip2 only on serine 227. In calcium switch assays, cells expressing rab11-fip2(s227a) showed a defect in the timely reestablishment of p120-containing junctional complexes.

SIGNOR-147118

O96013

P18084

1

phosphorylation

up-regulates

0.451

Pak4 specifically phosphorylated the integrin beta5 subunit at ser-759 and ser-762 within the beta5-sers-motif. Point mutation of these two serine residues abolished the pak4-induced cell migration, indicating a functional role for these phosphorylations in migration.

SIGNOR-165702

Q92985

P03209

0

transcriptional regulation

down-regulates quantity by repression

0.2

EBV Rta selectively down-regulates the expression of IRF3 and IRF7, the main regulators of the Type I IFNs.

SIGNOR-266645

P53350

P40763

0

transcriptional regulation

up-regulates quantity by expression

0.306

Stat3 directly activated transcription of PLK1 in esophageal cancer cells and mouse embryonic fibroblast cell NIH3T3.

SIGNOR-271690

P00519

P17676

1

phosphorylation

up-regulates

0.399

The y79 amino acid residue of c/ebpbeta was phosphorylated by c-abl or arg. The phosphorylation of c/ebpbeta resulted in an increased c/ebpbeta stability and a potentiation of c/ebpbeta transcription activation activity in cells

SIGNOR-186423

P24941

Q96PX1

1

phosphorylation

up-regulates activity

0.287

CDK2 promotes phosphorylation of RNF157 at the same Ser 660-663 residues that become phosphorylated downstream of combined PI3K and MAPK pathway activity.

SIGNOR-279016

Q9H2X9

Q9BYP7

0

phosphorylation

down-regulates activity

0.46

We have shown that with-no-lysine kinase 3 (WNK3) possesses several properties that suggest it could be the Cl−/volume-sensitive regulatory kinase that, in association with protein phosphatases, reciprocally modifies the phosphorylation/dephosphorylation states of the SLC12 proteins and thus their activities|WNK3 activates NKCC1/2 and NCC and inhibits the KCCs

SIGNOR-264628

P42345

P51397

1

phosphorylation

down-regulates activity

0.395

A critical step in autophagy induction comprises the inactivation of a key negative regulator of the process, the Ser/Thr kinase mammalian target of rapamycin (mTOR). Here we identify death-associated protein 1 (DAP1) as a novel substrate of mTOR that negatively regulates autophagy. Mapping of the phosphorylation sites and analysis of phosphorylation mutants indicated that DAP1 is functionally silenced in growing cells through mTOR-dependent phosphorylations on Ser3 and Ser51.

SIGNOR-259812

Q13535

Q8IUH4

1

phosphorylation

up-regulates activity

0.2

Collectively these results suggest that ZDHHC13 phosphorylation by ATR following UVB irradiation promotes its interaction with MC1R to stimulate MC1R palmitoylation.

SIGNOR-273517

P42229

P36888

0

phosphorylation

up-regulates activity

0.605

FLT3-ITDs induced a strong activation of STAT5. FLT3-ITD mutants induce an autophosphorylation of the receptor, interleukin 3-independent growth in Ba/F3 cells, and a strong STAT5 and mitogen-activated protein kinase (MAPK) activation.

SIGNOR-261516

P06493

Q92574

1

phosphorylation

down-regulates

0.489

Cell cycle-regulated phosphorylation of hamartin, the product of the tuberous sclerosis complex 1 gene, by cyclin-dependent kinase 1/cyclin b.Cyclin-dependent kinase 1 phosphorylates hamartin at three sites, one of which (thr417) is in the hamartin-tuberin interaction domain. Tuberin interacts with phosphohamartin, and tuberin expression attenuates the phosphorylation of exogenous hamartin. Hamartin with alanine mutations in the three cyclin-dependent kinase 1 phosphorylation sites increased the inhibition of p70s6 kinase by the hamartin-tuberin complex

SIGNOR-118584

Q12809

P17612

0

phosphorylation

up-regulates

0.307

Deletion of protein kinase a phosphorylation sites in the herg potassium channel inhibits activation shift by protein kinase afour consensus pka phosphorylation sites (s283a, s890a, t895a, s1137a)

SIGNOR-70726

P18031

P29320

1

dephosphorylation

down-regulates activity

0.417

Nevertheless, the finding that phosphorylation of the activation loop tyrosine (EphA3-Y779), a recently identified PTP1B substrate (Mertins et al., 2008), is essential for ligand-induced endocytosis (Janes et al., 2009)

SIGNOR-248426

Q13233

Q92918

0

phosphorylation

up-regulates

0.455

Hpk1 binds and phosphorylates mekk1 directly,

SIGNOR-43996

P05771

P04049

1

phosphorylation

up-regulates

0.445

Pkc can effectively phosphorylate raf-1, this is a direct effect of activated pkc and not the result of raf-1 autophosphorylation. the sites of pkc-mediated raf-1 phosphorylation are deduced to be ser497 and ser619.

SIGNOR-37474

O00401

Q07912

0

phosphorylation

up-regulates activity

0.307

Because TNK2 phosphorylation of WASL increases its actin nucleation activity ( xref ), we reasoned that it might be possible to complement the TNK2 deficiency by overexpression of WASL.|For NCK1, based on its reported binding to WASL and TNK2, we hypothesized that its function is to recruit WASL to TNK2, which could then activate WASL via phosphorylation ( xref ; xref ).

SIGNOR-280155

Q13107

O43395

1

deubiquitination

down-regulates activity

0.487

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

SIGNOR-271975

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

Q13164

Q15256

0

dephosphorylation

down-regulates activity

0.45

In this study we concentrated on whether and how PTP-SL, a kinase-interacting motif-containing PTP, might be involved in the down-regulation of the ERK5 signal|Whereas inactivation of ERK5 by PTP-SL monitored in vitro is most probably simply due to the dephosphorylation of tyrosine 220 in the activating TEY motif

SIGNOR-248721

Q13233

P40763

1

phosphorylation

up-regulates activity

0.291

Phosphorylation of s727 induces pin1 binding which increases transcription. Pin1 binding increases stat3 interaction with p300 and dna.

SIGNOR-236346

Q96L34

Q15831

0

phosphorylation

up-regulates

0.535

Lkb1 is a master kinase that activates 13 kinases of the ampk subfamily, including mark/par-1we recently demonstrated that the lkb1 tumour suppressor kinase, in complex with the pseudokinase strad and the scaffolding protein mo25, phosphorylates and activates amp-activated protein kinase (ampk). A total of 12 human kinases (nuak1, nuak2, brsk1, brsk2, qik, qsk, sik, mark1, mark2, mark3, mark4 and melk) are related to ampk. Here we demonstrate that lkb1 can phosphorylate the t-loop of all the members of this subfamily, apart from melk, increasing their activity >50-fold

SIGNOR-122682

P02545

P55212

0

cleavage

down-regulates

0.662

Lamin a breakdown is largely mediated by caspase-6 during the execution phase of apoptosis.

SIGNOR-83611

P29122

P04275

1

cleavage

up-regulates activity

0.293

Like PACE,PACE4 was able to process pro-vWF to its mature form, and efficient cleavage required both the P4 arginine and the P2 lysine

SIGNOR-260367

O95425

P53350

0

phosphorylation

up-regulates activity

0.2

PLK1 phosphorylates Ser238 of SVIL, which can promote the localization of SVIL to the central spindle and association with PRC1. Expression of a PLK1 phosphorylation site mutant, S238A-SVIL, inhibited myosin II activation at the equatorial cortex and induced aberrant furrowing.

SIGNOR-273729

Q12778

Q96J02

0

ubiquitination

down-regulates quantity by destabilization

0.258

Mechanistically, Itch ubiquitinates Foxo1 for proteasomal degradation.

SIGNOR-278698

P31749

Q969V5

0

ubiquitination

down-regulates quantity by destabilization

0.475

The results of the functional studies suggest that the degradation of Akt by MULAN suppresses cell proliferation and viability.

SIGNOR-252437

O43524

Q9Y243

0

phosphorylation

down-regulates quantity by destabilization

0.708

AKT phosphorylates FOXO3a at three conserved sites (Thr32, Ser253 and Ser315), therefore creating binding sites for the 14-3-3 chaperone proteins and leading to the active export of FOXO3a to the cytoplasm where it is targeted for proteasomal degradation.

SIGNOR-249644

Q01543

Q9UPS8

1

transcriptional regulation

down-regulates quantity by repression

0.284

In healthy individual, RUNX1/FLI1 complex negatively regulates ANKRD26 gene expression in MKs.

SIGNOR-266070

Q9H257

Q9BVG3

0

ubiquitination

up-regulates activity

0.51

Importantly, using in vitro ubiquitination assays with purified proteins, we verified that CARD9 is directly ubiquitinated by TRIM62 at residue K125; this ubiquitination is dependent on the ligase activity of TRIM62 and does not occur in CARD9 Delta11 (XREF_FIG).

SIGNOR-278552

Q05516

P49841

0

phosphorylation

up-regulates activity

0.2

Taken together, we conclude that S184 and T282 of ZBTB16 may be phosphorylated by GSK3beta in cells under serum starvation condition.

SIGNOR-279618

Q9HC16

P17612

0

phosphorylation

up-regulates

0.324

Here we show that pka binds and specifically phosphorylates a3g at thr32 in vitro and in vivo. This phosphorylation event reduces the binding of a3g to vif and its subsequent ubiquitination and degradation, and thus promotes a3g antiviral activity.

SIGNOR-181526

Q9UNE7

Q86WG3

1

polyubiquitination

down-regulates quantity by destabilization

0.378

CHIP e.g. was found to efficiently polyubiquitinate caytaxin in vitro, suggesting that it might influence caytaxin degradation in vivo.

SIGNOR-272651

P04798

P35869

0

transcriptional regulation

up-regulates quantity by expression

0.684

Kaempferol proved to be capable of inhibiting binding of agonist and agonist-induced formation of the AHR/ARNT DNA-binding complex and upregulation of the AHR target gene, CYP1A1.

SIGNOR-259909

P18850

Q16549

0

phosphorylation

up-regulates

0.2

We discovered that azc, an agent that causes the formation of abnormal proteins, stimulates the stress-activated kinase p38 mapk, which phosphorylates atf6

SIGNOR-89813

Q13043

Q9H8S9

1

phosphorylation

up-regulates

0.9

Mob1, when phosphorylated by MST1/2, binds to the autoinhibitory motif in Lats1/2, which in turn leads to the phosphorylation of the Lats activation loop (Lats1 S909 and Lats2 S872) and thereby an increase of their kinase activity

SIGNOR-201306

P63000

Q96N67

0

guanine nucleotide exchange factor

up-regulates activity

0.545

As a GEF, Dock7 exchanges GDP for GTP on Cdc42 and Rac1, causing their activation, followed by activation of downstream effectors, including the dephosphorylation (activation) of cofilin, a key regulator of actin turnover.

SIGNOR-261887

P10415

Q5S007

0

phosphorylation

up-regulates activity

0.329

Thus, we propose that Thr56 phosphorylation of Bcl-2 by LRRK2 G2019S might be a crucial step of mitochondrial disorder, which initiates the subsequent cellular damage in the context of PD relevant to G2019S.|We found that LRRK2 G2019S induced loss of the MMP was recovered in both GFP-Bcl-2 and GFP-M-Bcl-2 stable cells (XREF_FIG -lower panel).

SIGNOR-279531

Q13950

P06493

0

phosphorylation

up-regulates

0.479

In vitro kinase assays using recombinant cdc2 kinase showed that runx2 was phosphorylated at ser(451) the cdc2 inhibitor roscovitine dose dependently inhibited in vivo runx2 dna-binding activity during mitosis and the runx2 mutant s451a exhibited lower dna-binding activity and reduced stimulation of anchorage-independent growth relative to wild type runx2.

SIGNOR-143586

O14974

O75116

0

phosphorylation

down-regulates activity

0.785

Rho kinase is known to control smooth muscle contractility by phosphorylating the 110 kDa myosin-targetting subunit (MYPT1) of the myosin-associated form of protein phosphatase 1 (PP1M). Phosphorylation of MYPT1 at Thr695 has previously been reported to inhibit the catalytic activity of PP1. Here, we show that the phosphorylation of Thr850 by Rho kinase dissociates PP1M from myosin, providing a second mechanism by which myosin phosphatase activity is inhibited.

SIGNOR-249164

O14672

P46531

1

cleavage

up-regulates activity

0.782

ADAM10-mediated Notch1 cleavage is the rate limiting-step for release of the NICD and subsequent activation of Notch1 signaling. In T cells ADAM10-mediated Notch1 shedding controls T cell development

SIGNOR-259838

Q13315

Q13541

1

phosphorylation

down-regulates

0.512

Here we report that atm... phosphorylates 4e-bp1 at ser 111cells lacking atm kinase activity exhibit a significant decrease in the insulin-induced dissociation of 4e-bp1 from eif-4e.

SIGNOR-85619

P24844

Q05397

0

phosphorylation

up-regulates activity

0.286

It indicates that FAK positively regulates the phosphorylation of MLC2.

SIGNOR-280098

Q13144

P19784

0

phosphorylation

up-regulates activity

0.37

Two conserved sites (Ser712/713) are phosphorylated by casein kinase 2. They lie at the extreme C-terminus and are required for the interaction of eIF2Bepsilon with its substrate, eIF2, in vivo and for eIF2B activity in vitro.

SIGNOR-250990

P40426

P55075

1

transcriptional regulation

down-regulates quantity by repression

0.2

Our results in ES cells suggest that Engrailed inhibits Fgf8 expression in the absence of Pbx1. We identified single Engrailed- and Pbx-binding sites in the Fgf8 intron that inhibit expression of Fgf8 in mouse ES cells, but that together can allow full Fgf8 expression. Our data support the model that Engrailed heterodimerized with Pbx might activate transcription, while Engrailed or Pbx proteins alone might repress transcription

SIGNOR-265779

O14672

P16070

1

cleavage

up-regulates activity

0.346

The ADAM proteases are best known for their role in shedding the extracellular domain of transmembrane proteins. Among the transmembrane proteins shed by ADAM10 are notch, HER2, E-cadherin, CD44, L1 and the EGFR ligands, EGF and betacellulin.

SIGNOR-259847

O60260

Q13501

1

ubiquitination

down-regulates quantity by destabilization

0.2

Once activated, parkin interacts with and subsequently ubiquitinates p62 at the K13 residue, resulting in the degradation of p62 via the proteasomal dependent pathway.

SIGNOR-278524

P10636

Q7KZI7

0

phosphorylation

down-regulates activity

0.707

We have studied the relationship between the phosphorylation oftau by several kinases (MARK, PKA, MAPK, GSK3) and its assembly into PHFs. By contrast, MARK and PKA phosphorylate several sites within the repeats (notably theKXGS motifs including Ser262, Ser324, and Ser356, plus Ser320); in addition PKA phosphorylates somesites in the flanking domains, notably Ser214. This type of phosphorylation strongly reduces tau’s affinityfor microtubules, and at the same time inhibits tau’s assembly into PHFs.

SIGNOR-275436

Q00535

O14490

1

phosphorylation

down-regulates quantity by destabilization

0.408

Taken together, these sets of data suggest that Abeta triggers the phosphorylation of GKAP by cdk5 at the serine residues S77 and S111 that in turn are crucial for GKAP degradation.

SIGNOR-279153

P06493

Q8WVD3

1

phosphorylation

up-regulates activity

0.2

Altogether, our results suggest RNF138 is phosphorylated at position T27 in a CDK1- and CDK2-dependent manner.Altogether, our results suggest RNF138 is phosphorylated at position T27 in a CDK1- and CDK2-dependent manner.

SIGNOR-277832

P48730

P11308

1

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

P12036

P28482

0

phosphorylation

up-regulates activity

0.368

The fraction containing Erk2, as well as bacterially expressed Erk1 and Erk2, phosphorylated all types of KSP motifs in peptides (KSPXK, KSPXXK, KSPXXXK, and KSPXXXXK) derived from NF-M and NF-H. They also phosphorylated an expressed 24 KSPXXXK repeat NF-H polypeptide, an expressed NF-H as well as dephosphorylated native rat NF-H, and NF-M proteins with accompanying decreases in their respective electrophoretic mobilities. |Our data on primary hippocampal cells also showed an inhibition of neurite outgrowth by the drug that was accompanied by inhibition of MAP, NF-H, and NF-M phosphorylation.

SIGNOR-249424

O43561

P45983

0

phosphorylation

down-regulates

0.308

Lat, an adapter protein essential for t-cell signaling, is phosphorylated at its thr 155 by erk in response to t-cell receptor stimulation. Thr 155 phosphorylation reduces the ability of lat to recruit plcgamma1 and slp76, leading to attenuation of subsequent downstream events such as [ca2+]i mobilization and activation of the erk pathway.Mutational analysis revealed that t155 but not t94 or t140 is the site of jnk-mediated phosphorylation (figure 2b). Erk also phosphorylated lat at t155 (figure 2c), whereas p38, which was able to phosphorylate atf2, failed to induce threonine phosphorylation of lat (figure 2d). These results indicate that lat is directly phosphorylated by erk and jnk at the same site, t155.

SIGNOR-125774

Q02763

P35590

1

phosphorylation

up-regulates activity

0.348

Thus, Tie2 was able to induce Tie1 phosphorylation.|When cotransfected, Tie2 formed heteromeric complexes with Tie1, enhanced Tie1 activation, and induced phosphorylation of a kinase-inactive Tie1 in a ligand-dependent manner.

SIGNOR-279769

Q04759

P35568

1

phosphorylation

down-regulates activity

0.567

Protein kinase C Theta inhibits insulin signaling by phosphorylating IRS1 at Ser(1101).

SIGNOR-260906

P12931

Q01973

0

phosphorylation

up-regulates

0.318

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

SIGNOR-196751

Q13571

P46934

0

ubiquitination

up-regulates activity

0.476

These results suggest that LAPTM5 ubiquitination is mediated by Nedd4.|Thus, Nedd4 promotes the recruitment of GGA3 to LAPTM5, allowing LAPTM5 translocation from the Golgi to the lysosome with the aid of GGA3.

SIGNOR-278768

P36894

Q9HAU4

0

ubiquitination

down-regulates

0.552

Smurf1 and smurf2 are e3 ubiquitin ligases known to suppress tgf-beta signaling through degra-dation of smads and receptors for tgf-beta and bmps

SIGNOR-192898

O43248

P04271

1

transcriptional regulation

up-regulates quantity by expression

0.252

HOXC6 and HOXC11 increase transcription of S100beta gene in BrdU-induced in vitro differentiation of GOTO neuroblastoma cells into Schwannian cells.

SIGNOR-261647

P06493

O00399

1

phosphorylation

up-regulates activity

0.307

Here, we show that the p27/p25 heterodimer undergoes mitotic phosphorylation by cyclin‐dependent kinase 1 (Cdk1) at a single site, p27 Thr186, to generate an anchoring site for polo‐like kinase 1 (Plk1) at kinetochores.

SIGNOR-264777

Q96EB6

Q9Y618

1

null

up-regulates

0.494

In differentiated adipocyte cell lines, SIRT1 inhibits adipogenesis and enhances fat mobilization through lipolysis by suppressing the activity of PPARγ. SIRT1 achieves this by promoting the assembly of a corepressor complex, involving NCoR1 and SMRT, on the promoters of PPARγ target genes to repress their transcription.

SIGNOR-253506

Q8WVD3

P24941

0

phosphorylation

up-regulates activity

0.2

Altogether, our results suggest RNF138 is phosphorylated at position T27 in a CDK1- and CDK2-dependent manner.Altogether, our results suggest RNF138 is phosphorylated at position T27 in a CDK1- and CDK2-dependent manner.

SIGNOR-277831

P61006

Q9Y6E0

0

phosphorylation

up-regulates activity

0.275

In a screen for Rab8A kinases we identify TAK1 and MST3 kinases that can efficiently phosphorylate the Switch II residue Threonine72 (Thr72) in a similar manner as LRRK2 in vitro. |Overall our data suggests that the phosphorylation of Rab8A at Ser111 may influence Switch II-binding by regulators, thus disrupting interactions with its cognate GEF and moderately impairs its interaction with GAPs.|The antagonistic interplay between Ser111 phosphorylation and Thr72 phosphorylation is genetically concordant with how respective mutations in PINK1 and LRRK2 cause Parkinson’s disease

SIGNOR-260265

Q16539

P35813

0

dephosphorylation

down-regulates activity

0.408

Moreover, when expressed in mammalian cells, pp2ca inhibited the activation of the p38 and jnk cascades induced by environmental stresses. Both in vivo and in vitro observations indicated that pp2ca dephosphorylated and inactivated mapkks (mkk6 and sek1) and a mapk (p38) in the stress-responsive mapk cascades. Furthermore, a direct interaction of pp2ca and p38 was demonstrated by a co-immunoprecipitation assay

SIGNOR-59618

P15927

Q13315

0

phosphorylation

up-regulates

0.809

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

SIGNOR-121861

Q12979

P63000

1

gtpase-activating protein

down-regulates activity

0.504

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-260525

Q15418

P67809

1

phosphorylation

up-regulates

0.543

We therefore conclude that rsk1/rsk2 are novel activators of yb-1, able to phosphorylate the serine 102 residue.

SIGNOR-182497

P68400

Q01534

1

phosphorylation

up-regulates activity

0.2

CK2-dependent C-terminal phosphorylation at T300 directs the nuclear transport of TSPY protein

SIGNOR-250969

P68400

P55087

1

phosphorylation

down-regulates activity

0.416

We found that the stress-induced kinase casein kinase (CK)II phosphorylates the Ser276 immediately preceding the tyrosine motif, increasing AQP4-mu 3A interaction and enhancing AQP4-lysosomal targeting and degradation. AQP4 phosphorylation by CKII may thus provide a mechanism that regulates AQP4 cell surface expression. | To determine whether Ser276 is an actual CKII substrate, we used GST–AQP4-Cter proteins in which only one out of the three C-terminal CKII consensus sites was sequentially conserved (Ser276, Ser285 and Ser315, respectively). Figure 7B (right panel) shows that the three serine residues, including Ser276, were indeed efficiently phosphorylated by CKII.

SIGNOR-250827

P12931

P60174

1

phosphorylation

up-regulates quantity by stabilization

0.2

As shown in xref , Tim was phosphorylated by both Hck and c-Src, and to a lesser extent by Fyn and c-Yes.|In the case of Hck and Fyn, co-expression led to enhanced Tim turnover, while c-Src and c-Yes promoted Tim stability.

SIGNOR-280136

P00441

O96017

0

phosphorylation

up-regulates activity

0.376

ROS signaling is mediated by Mec1/ATM and its effector Dun1/Cds1 kinase, through Dun1 interaction with Sod1 and regulation of Sod1 by phosphorylation at S60, 99. In the nucleus, Sod1 binds to the promoters and regulates the expression of oxidative resistance and repair genes.

SIGNOR-262794

P12931

P50402

1

phosphorylation

down-regulates

0.451

Src phosphorylated emerin specifically at y59, y74 and y95; interestingly y-to-f substitutions at identified src sites reduced recombinant emerin binding to endogenous baf

SIGNOR-188308

Q15691

P48730

0

phosphorylation

up-regulates activity

0.505

We further show that casein kinase 1\u03b4 binds and phosphorylates EB1 and promotes microtubule growth.

SIGNOR-279165

P19525

P52564

1

phosphorylation

up-regulates activity

0.2

Consistent with this observation, PKR was capable of activating MKK6 as assessed in a coupled kinase assay containing the components of the p38 MAPK pathway.|In vitro kinase assays revealed that MKK6 was efficiently phosphorylated by PKR, and this could be inhibited by 2-aminopurine.

SIGNOR-279707

Q13131

P46527

1

phosphorylation

up-regulates quantity by stabilization

0.267

P27Kip1-Mediated Cell Survival Is Dependent on AMPK-Specific Thr198 Phosphorylation|AMPK-dependent phosphorylation of p27Kip1 on Thr198 promotes p27Kip1 protein stability, resulting in more autophagy and less apoptosis.

SIGNOR-259859

Q9BWW4

P06239

0

phosphorylation

up-regulates activity

0.2

The Src tyrosine kinase inhibitor PP2 blocked the nuclear translocation of Ssdp1. Western blot analysis showed that co-expression of Ssdp1 and Lck in 293T cells induces Ssdp1 phosphorylation. Mutation of the Ssdp1 N terminal tyrosine residues 23 and 25 markedly reduced both the phosphorylation and the nuclear localization of Ssdp1. Lck enhanced the transcriptional activity of Ssdp1 in the context of known components of a LIM-homeodomain (LIM-HD)/cofactor complex.

SIGNOR-273648

P10275

P12931

0

phosphorylation

up-regulates activity

0.76

In addition to the ability of Src to promotes castration resistant progression and AR activation, Src is involved in regulating prostate cancer cell migration, invasion, and metastasis and affects bone remodeling.|These data suggest that downstream of cell surface receptors, Ack1 mediates AR tyrosine phosphorylation at Tyr 267 and Src mediates AR tyrosine phosphorylation at Tyr 534.

SIGNOR-278168

P22681

O00459

1

ubiquitination

down-regulates

0.606

Cbl-b, a ring-type e3 ubiquitin protein ligase, is implicated in setting the threshold of t lymphocyte activation. The p85 regulatory subunit of phosphatidylinositol 3 kinase (pi3k) was identified as a substrate for cbl-b. We have shown that cbl-b negatively regulated p85 in a proteolysis-independent manner.

SIGNOR-110063

P17612

P35367

1

phosphorylation

down-regulates

0.2

Two amino acid residues (ser396, ser398) on hr1 were determined to be pkc phosphorylation sites by in vitro phosphorylation studies.Site-directed mutagenesis studies suggests that the ser398 residue was primarily involved in pkc-mediated desensitization. Possibly, phosphorylation of the residues is required for receptor transport from endosomes to lysosomes.

SIGNOR-128411

Q9UHD2

P08631

0

phosphorylation

down-regulates activity

0.2

The Src family kinases (SFKs) Lck, Hck, and Fgr directly phosphorylate TBK1 at Tyr354/394, to prevent TBK1 dimerization and activation.

SIGNOR-276727

Q9NR97

Q9NWF9

0

polyubiquitination

down-regulates quantity by destabilization

0.257

E3 ligase RNF216 (ring finger protein 216) targets TLR8 for ubiquitination and degradation.

SIGNOR-272257

P00519

O15269

1

phosphorylation

down-regulates

0.2

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

SIGNOR-202003

P04637

Q6PCD5

0

ubiquitination

up-regulates quantity by stabilization

0.361

RFWD3 is a positive regulator of p53 abundance and regulates the G1 checkpoint in response to IR. We found that an E3 ubiquitin ligase RFWD3 (RNF201/FLJ10520) forms a complex with Mdm2 and p53 to synergistically ubiquitinate p53 and is required to stabilize p53 in the late response to DNA damage.

SIGNOR-271944

Q96AC1

Q8IWT3

0

ubiquitination

down-regulates quantity by destabilization

0.2

M-phase-specific CDK1–cyclin B1 complex directly binds KIND1 and KIND2 and phosphorylates a conserved proline-directed CDK1 consensus motif in the flexible and intrinsically disordered loop of the F1 domain. This then results in the recruitment of the CUL9–FBXL10 complex, modification with K48-linked polyubiquitin chains and proteasomal degradation of KIND1 and KIND2.

SIGNOR-276717

Q96PY6

Q9UKI8

0

phosphorylation

up-regulates activity

0.29

TLK1 phosphorylated NEK1 at T141, which lies in the kinase domain, and caused an increase in its activity.

SIGNOR-275840