GleghornLab/Signor_2class · Datasets at Hugging Face

IdA string	IdB string	labels int64	mechanism string	effect string	score float64	sentence string	signor_id string
P54253	O75582	0	phosphorylation	up-regulates quantity by stabilization	0.26	In summary, the data from the cell based screen, biochemical studies and genetic interactions strongly suggest that MSK1 phosphorylates ATXN1 and regulates its stability.	SIGNOR-279109
O14548	Q99683	0	phosphorylation	up-regulates activity	0.2	Phosphorylation of EB1 by ASK1 promotes the binding of EB1 to CLIP-170 and p150 glued.	SIGNOR-278341
Q9NWF9	Q9NR96	1	ubiquitination	down-regulates quantity by destabilization	0.406	Here we describe how a RING finger protein, Triad3A, acts as an E3 ubiquitin-protein ligase and enhances ubiquitination and proteolytic degradation of some TLRs. Triad3A overexpression promoted substantial degradation of TLR4 and TLR9 with a concomitant decrease in signaling, but did not affect TLR2 expression or signaling.	SIGNOR-271505
P17252	Q13769	1	phosphorylation	up-regulates	0.327	We conclude m-csf-mediated activation of pkcalpha can potentiate fmip action to initiate survival/differentiation signaling.	SIGNOR-126572
P28482	P16949	1	phosphorylation	down-regulates	0.452	Involved in the regulation of the microtubule (mt) filament system by destabilizing microtubules. Prevents assembly and promotes disassembly of microtubules. The kinases involved in phosphorylating stmn ser-16 and ser-63 include camp-dependent protein kinase (pka) and pak1, whereas stmn ser-25 and ser-38 have been shown to be targets for proline-directed serine/threonine kinases such as cyclin-dependent kinases, erk1/2, and members of the p38 mapk subfamily.	SIGNOR-166686
Q05513	P35222	1	phosphorylation	down-regulates quantity by destabilization	0.599	Yap and β-catenin are direct substrates of PKCζ. Similar MS/MS analysis to map the sites phosphorylated in β-catenin by PKCζ identified S45 and several sites of low abundance that included S552 and S675 (Figure S3C).	SIGNOR-276880
Q07820	Q7Z6Z7	0	ubiquitination	down-regulates quantity by destabilization	0.502	Mule was identified as Mcl-1 ubiquitin ligase E3 to promote Mcl-1 degradation via the proteasomal pathway [46]. We found that knockdown of Mule (Fig. 4C) but not β-TRCP or FBXW7 (data not shown) prevented Mcl-1 downregulation caused by PKCη depletion.	SIGNOR-261909
Q07820	Q13627	0	phosphorylation	up-regulates quantity	0.2	Furthermore, DYRK1A likely directly bound and phosphorylated Mcl-1, thereby enhancing Mcl-1 protein stability and contributing to the development of acquired resistance to Bcl-2 inhibitors.\|DYRK1A upregulates Mcl-1 expression in NSCLC cells.\|We demonstrated that DYRK1A suppression by siRNA or harmine decreased the phosphorylation of Mcl-1 at Ser159/Thr163.	SIGNOR-279704
P01112	P12931	0	phosphorylation	down-regulates activity	0.775	Src binds to and phosphorylates GTP-, but not GDP-, loaded Ras on a conserved Y32 residue within the switch I region in vitro and that in vivo, Ras-Y32 phosphorylation markedly reduces the binding to effector Raf and concomitantly increases binding to GTPase-activating proteins and the rate of GTP hydrolysis	SIGNOR-252093
Q66K74	Q13618	0	ubiquitination	down-regulates quantity	0.242	Gigaxonin is the substrate-specific adaptor for a new Cul3-E3-ubiquitin ligase family that promotes the proteasome dependent degradation of its partners MAP1B, MAP8 and tubulin cofactor B.	SIGNOR-268947
P17947	P49841	0	phosphorylation	down-regulates quantity by destabilization	0.2	We demonstrate that GSK3β phosphorylates PU.1 at Ser41 and Ser140 leading to its recognition and subsequent ubiquitin-mediated degradation by E3 ubiquitin ligase FBW7.	SIGNOR-277541
P43405	P29350	0	dephosphorylation	down-regulates	0.737	We propose that shp1 can dephosphorylate sites in zap-70 and syk that are involved in coupling these kinases to downstream signaling cascades, including erk2 and elements of the il-2 gene.	SIGNOR-70234
Q9H3R0	P68431	1	demethylation	down-regulates activity	0.2	As one member of the Jumonji-C histone demethylase family, JMJD2C has the ability to demethylate tri- or di-methylated histone 3 and 2 in either K9 (lysine residue 9) or K36 (lysine residue 36) sites by an oxidative reaction, thereby affecting heterochromatin formation, genomic imprinting, X-chromosome inactivation, and transcriptional regulation of genes.JMJD2C has been proved to be a demethylase for H3K9 methylation, in the manner of catalyzing the demethylation of H3K9me3/me2 (the known repressive markers of gene regulation), a histone mark found in heterochromatin associated with euchromatic transcriptional silencing and heterochromatin formation	SIGNOR-263864
Q96QZ7	Q15418	0	phosphorylation	up-regulates activity	0.286	We report herein that p90RSK associates with MAGI1 in ECs and executes 2 independently regulated PTMs of MAGI1: S741 phosphorylation and K931 deSUMOylation. MAGI1-S741 phosphorylation is vital for Rap1 activation.	SIGNOR-273837
P27361	P17655	1	phosphorylation	up-regulates	0.565	Epidermal growth factor activates m-calpain (calpain ii), at least in part, by extracellular signal-regulated kinase-mediated phosphorylation.We now show that erk directly phosphorylates and activates m-calpain both in vitro and in vivo. We identified serine 50 as required for epidermal growth factor (egf)-induced calpain activation in vitro and in vivo.	SIGNOR-123083
Q96A00	Q05513	0	phosphorylation	up-regulates activity	0.277	A major kinase for GPCR‐induced CPI‐17 phosphorylation is PKC which is activated by the PLCbeta‐produced signaling messenger diacylglycerol (DAG). It phosphorylates CPI‐17 at Thr38 residue that directly docks at the active site of MLCP, thereby inhibiting its activity and promoting an increase of phosphorylation of myosin and of other MLCP.	SIGNOR-249261
P42263	Q5JU85	0	relocalization	up-regulates quantity	0.2	BRAG1 increases the synaptic recycling pool of AMPARs.these data suggest that the BRAG1 enhancement of AMPAR transmission is mediated by the increased expression of the recycling pool of synaptic GluA2/3 receptors.	SIGNOR-264914
P48729	Q9UKV8	1	phosphorylation	down-regulates activity	0.369	Our experiments demonstrated that target engagement by AGO2 stimulates its hierarchical, multi-site phosphorylation by CSNK1A1 on a series of highly conserved residues (S824-S834).Although this impairs target binding, dephosphorylation by ANKRD52-PPP6C allows AGO2 to engage new targets. Inactivation of this cycle strongly inhibits global miRNA-mediated repression.	SIGNOR-276510
Q13887	P04150	0	transcriptional regulation	up-regulates quantity by expression	0.292	We show that in addition, DEX-bound GR directly promotes the expression of adipogenic TFs, including C/EBPβ, Klf5, Klf9, and C/EBPα	SIGNOR-256118
Q9NZQ7	Q8TCJ2	0	glycosylation	up-regulates quantity by stabilization	0.2	Together, these results support a notion that the two STT3 isoforms regulate EMT-mediated PD-L1 induction through PD-L1 protein N-glycosylation and stabilization.	SIGNOR-274976
P28482	Q7LDG7	1	phosphorylation	down-regulates activity	0.396	ERK2 phosphorylates RasGRP2 at Ser394 located in the linker region implicated in its autoinhibition.	SIGNOR-279537
P53350	O95425	1	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
P19174	Q96EB6	0	deacetylation	up-regulates activity	0.2	The histone acetyltransferase GCN5 (general control non-repressed protein 5) acetylates PGC-1alpha and suppresses its transcriptional activity, whereas sirtuin 1 deacetylates and activates PGC-1alpha.	SIGNOR-275499
P20823	O60656	1	transcriptional regulation	up-regulates quantity by expression	0.267	Using gel shift and functional assays, HNF1alpha was demonstrated to bind to and activate the UGT1A8, -1A9, and -1A10 promoters. In contrast, Cdx2 bound to and activated the UGT1A8 and -1A10 promoters but could not activate the UGT1A9 promoter.	SIGNOR-253973
Q16891	P17612	0	phosphorylation	down-regulates activity	0.2	PKA directly phosphorylated the Ser528 residue of MIC60. Phosphorylation of MIC60 Interrupts Parkin Recruitment and Formation of the MICOS Complex	SIGNOR-266302
Q96P20	O95376	0	ubiquitination	up-regulates activity	0.444	ARIH2 can ubiquitinate NLRP3 via the NACHT domain of NLRP3, and the RING2 domain of ARIH2 is required for NLRP3 ubiquitination 65.\|Overexpression of ARIH2 promotes NLRP3 ubiquitination and inhibits NLRP3 inflammasome activation 65.	SIGNOR-278686
P61586	Q9NR80	0	guanine nucleotide exchange factor	up-regulates activity	0.667	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-260531
Q8N6T7	P31749	0	phosphorylation	down-regulates activity	0.532	AKT1 interacts with and phosphorylates SIRT6 on Ser 338.\|Because AKT1 suppresses SIRT6 protein abundance by decreasing its stability, we investigated whether MDM2 is involved in this process.	SIGNOR-278465
O15084	Q13557	0	phosphorylation	down-regulates activity	0.2	We provide evidence for a dual kinase-mediated regulation of the PITK holoenzyme whereby PITK phosphorylation at S1017 is catalyzed by calcium/calmodulin-dependent kinase II-delta (CaMKIIdelta), promoting the subsequent phosphorylation of S1013 by glycogen synthase kinase-3 (GSK3) in vitro.\|the phosphorylation of PITK at these specific residues altered PP1 binding and subsequent PITK-directed dephosphorylation of hnRNP K	SIGNOR-264793
Q9UKW4	P12931	0	phosphorylation	up-regulates	0.325	Activation of rac1 and the exchange factor vav3 are involved in npm-alk signaling in anaplastic large cell lymphomas.	SIGNOR-159240
P31751	O60343	1	phosphorylation	down-regulates activity	0.642	AKT2 phosphorylation blocks AS160 function enhancing GLUT4 intracellular vesicular transport, and as such promotes glucose uptake following insulin release .\|Notable mechanisms promoting this involves AKT2 mediated phosphorylation of the Rab-GTPase-activating protein TBC1D4, also known as AS160.	SIGNOR-280179
Q8NHV4	P06493	0	phosphorylation	up-regulates activity	0.585	Here we report that the function of Nedd1 is regulated by Cdk1 and Plk1. During mitosis, Nedd1 is firstly phosphorylated at T550 by Cdk1, which creates a binding site for the polo-box domain of Plk1. Then, Nedd1 is further phosphorylated by Plk1 at four sites: T382, S397, S637 and S426. The sequential phosphorylation of Nedd1 by Cdk1 and Plk1 promotes its interaction with gamma-tubulin for targeting the gammaTuRC to the centrosome and is important for spindle formation.	SIGNOR-272973
P30304	P11802	1	dephosphorylation	up-regulates activity	0.705	Invalidation of CDK4 has no impact by itself on the cell proliferation, but invalidation of CDC25A prevents the dephosphorylation of CDK6 (Y24) and CDK4 (Y17) residues, and impedes their association with CCNDs.	SIGNOR-267568
O43318	Q9Y572	1	phosphorylation	up-regulates activity	0.2	Collectively, TAK1 activates RIPK3, RIPK3 activates TAK1, and RIPK1 activates RIPK3 and facilitates interaction between TAK1 and RIPK3.\|We found that prolonged and hyperactivation of TAK1 induced phosphorylation and activation of RIPK3, leading to necrosis without caspase activation.	SIGNOR-279634
Q16665	Q9H4B4	0	phosphorylation	down-regulates	0.348	Polo-like kinase 3 functions as a tumor suppressor and is a negative regulator of hypoxia-inducible factor-1 alpha under hypoxic conditionsplk3 can potentially inhibit hif-1_ by physical interaction and direct phosphorylation	SIGNOR-178743
Q86WV6	P35813	0	dephosphorylation	down-regulates activity	0.2	Collectively, our findings suggest that the overexpression of PPM1A antagonizes the STING- and TBK1-induced type I interferon signaling pathway.\|First, PPM1A directly dephosphorylated STING, likely via its S358 site (Figs.\|Moreover, our study demonstrates that while TBK1 enhances STING aggregation in a kinase activity-dependent manner, PPM1A suppresses STING aggregation by dephosphorylating both STING and TBK1.	SIGNOR-276958
Q14247	P11362	0	phosphorylation	down-regulates	0.313	Cortactin, which is an actin-binding protein that also plays a role in actin cytoskeleton dynamics (45), was phosphorylated on tyr-446 in our assay (by fgfr1).Phosphorylation of these residues attenuates the f-actin cross-linking activity	SIGNOR-98618
P29353	Q05397	0	phosphorylation	up-regulates activity	0.674	In vitro, FAK directly phosphorylated Shc Tyr-317 to promote Grb2 binding. FAK can associate and directly phosphorylate Shc at Tyr-317 to promote Grb2 binding and low-level signaling to ERK2.	SIGNOR-259854
Q16539	Q13950	1	phosphorylation	up-regulates activity	0.367	Mechanistic analysis revealed that the TAK1–MKK3/6–p38 MAPK axis phosphorylated Runx2, promoting its association with the coactivator CREB-binding protein (CBP), which was required to regulate osteoblast genetic programs. These findings reveal an in vivo function for p38β and establish that MAPK signaling is essential for bone formation in vivo.	SIGNOR-255777
Q9Y6Q9	P06493	0	phosphorylation	down-regulates	0.368	We demonstrate that aib1 is phosphorylated on ser728 and ser867 by cdk1/cyclin b at the onset of mitosis and remains phosphorylated until exit from m phase.	SIGNOR-195233
Q14694	P04637	1	deubiquitination	up-regulates quantity by stabilization	0.662	Since USP10 is known as a deubiquitinating protease of p53 (Yuan et al., 2010), inhibition of USP10 by spautin-1 may promote the degradation of p53.	SIGNOR-260297
Q05655	P40189	1	phosphorylation	up-regulates activity	0.334	Finally, we identified Thr-890, a putative PKC phosphorylation site on gp130, to be critical for the effect of PKCdelta. Our data indicate that PKCdelta plays important regulatory roles in IL-6 signaling.	SIGNOR-249177
O43280	P06493	0	phosphorylation	up-regulates activity	0.268	Ewald et al. reported that at the G1/S transition, cyclin-dependent kinase 1 (CDK1) phosphorylates and activates the neutral trehalase (NTH1) to funnel trehalose into glycolysis (Ewald et al. xref ).	SIGNOR-280206
Q05086	P04637	1	ubiquitination	down-regulates quantity	0.681	E6-AP also directly ubiquitylated p53 in an in vitro ubiquitylation assay.\|Our result suggests that E6-AP not only enhances the degradation of p53 but also regulates the neuronal cell growth.	SIGNOR-278681
Q00535	Q9UD71	1	phosphorylation	up-regulates activity	0.777	We find that DARPP-32 is converted into an inhibitor of PKA when phosphorylated at threonine 75 by cyclin-dependent kinase 5 (Cdk5). Cdk5 phosphorylates DARPP-32 in vitro and in intact brain cells. Phospho-Thr 75 DARPP-32 inhibits PKA in vitro by a competitive mechanism.	SIGNOR-250671
O14672	P12830	1	cleavage	up-regulates activity	0.548	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-259846
Q14693	P12931	0	phosphorylation	up-regulates activity	0.2	Obesity-associated microenvironmental factors and other Src-activating growth factors, including the epidermal growth factor, activate Src and promote Src-mediated lipin-1 phosphorylation on Tyr398, Tyr413 and Tyr795 residues. The tyrosine phosphorylation of lipin-1 markedly increases its PAP activity, accelerating the synthesis of glycerophospholipids and triglyceride.	SIGNOR-277291
P35236	Q05655	0	phosphorylation	up-regulates activity	0.2	HePTP is phosphorylated by PKC isozymes at Ser-225 in vitro. While all isozymes phosphorylated Ser-225 predominantly and Ser-113 to a lesser extent (Fig. (Fig.5),5), they differed strikingly in how much 32P they incorporated into HePTP during the 30-min assay. PKC θ was the most efficient, while PKC ζ and PKC μ were clearly less potent; PKC δ, ɛ, and η were quite inefficient.	SIGNOR-276048
P78504	O76050	0	ubiquitination	down-regulates quantity by destabilization	0.707	We find that NEDD4 targets an RNA-binding protein, NANOS2, in spermatogonia to destabilize it, leading to cell differentiation.\|Jagged1 is also regulated by the E3 ligase Neuralized-like1 (Neurl1), which induces the monoubiquitination of membrane tethered Jagged1 in the C-terminal region.	SIGNOR-278772
P04637	O43683	0	phosphorylation	up-regulates activity	0.484	In addition, purified Bub1 directly phosphorylates p53 on Ser-37 in vitro , possibly inducing cellular senescence [ xref ].\|Studies have shown that depletion and inhibition of Aurora A, Aurora B, Plk1, or Bub1 induces cellular senescence or cell death in a p53 dependent or -independent but p73 dependent manner in many different cell types , - ].	SIGNOR-280199
P29350	P35222	1	dephosphorylation	down-regulates quantity by destabilization	0.558	Because SHP-1 can dephosphorylate residues Y86 and Y654 on the \u03b2-catenin protein, these residues were therefore mutated into phenylalanine and the transcriptional activity of the subsequent \u03b2-catenin mutants analyzed: \u03b2-catenin/Y86F, \u03b2-catenin/Y654F and \u03b2-catenin/Y86F/Y654F. As shown in Fig.\u00a03 B, the mutants \u03b2-catenin/Y86F, \u03b2-catenin/Y654F and \u03b2-catenin/Y86F/Y654F had a significantly reduced transcriptional activity in comparison to wild-type \u03b2-catenin.\|SHP-1 inhibits \u03b2-catenin function by inducing its degradation and interfering with its association with TATA-binding protein.	SIGNOR-277014
Q9P286	O95831	1	phosphorylation	down-regulates activity	0.2	Our results show that PAK5 can phosphorylate Thr-281 of AIF, which is included in its NLS1 sequence.\|These results suggested that PAK5 inhibited AIF from entering the nucleus through phosphorylation of AIF T281 site, thus inhibiting cell apoptosis.	SIGNOR-279085
Q9BYT3	P32754	1	phosphorylation	down-regulates quantity by destabilization	0.2	Decreased expression of 4-hydroxyphenylpyruvic acid dioxygenase (HPD), a key enzyme for tyrosine metabolism, is a cause of human tyrosinemia. However, the regulation of HPD expression remains largely unknown. Here, we demonstrate that molecular chaperone TTC36, which is highly expressed in liver, is associated with HPD and reduces the binding of protein kinase STK33 to HPD, thereby inhibiting STK33-mediated HPD T382 phosphorylation. The reduction of HPD T382 phosphorylation results in impaired recruitment of FHA domain-containing PELI1 and PELI1-mediated HPD polyubiquitylation and degradation.	SIGNOR-272958
Q09472	P84022	1	acetylation	up-regulates quantity by stabilization	0.736	Smad proteins are crucial for the intracellular signaling of transforming growth factor-beta (TGF-beta). Upon their receptor-induced activation, Smad proteins are phosphorylated and translocated to the nucleus to activate the transcription of a select set of target genes. Here, we show that the co-activator p300/CBP bound and acetylated Smad3 as well as Smad2 in vivo, and that the acetylation was stimulated by TGF-beta.A major acetylation site of Smad3 by p300/CBP is Lys-378 in the MH2 domain (Smad3C) known to be critical for the regulation of transcriptional activity.	SIGNOR-260431
O00303	P46531	1	deubiquitination	up-regulates	0.421	The activated form of notch needs to be deubiquitinated before being processed by the gamma-secretase activity and entering the nucleus, where it fulfills its transcriptional function. The enzyme accounting for this deubiquitinase activity is eif3f, known so far as a translation initiation factor.	SIGNOR-170158
P62140	P35240	1	dephosphorylation	up-regulates	0.378	When serine 518 is dephosphorylated by the myosin phosphatase mypt-1-pp1?, The tumor suppressor function of merlin is activated, inhibiting the ras signaling pathway and leading to growth arrest	SIGNOR-159836
P35498	Q96PU5	0	ubiquitination	down-regulates quantity by destabilization	0.292	The control of Nav density at the cell membrane is crucial to ensuring normal neuronal excitability. Navs are subject to posttranslational modifications that may influence their cell membrane availability. Ubiquitylation is a key process that orchestrates the internalization and subsequent degradation or recycling of Navs. This is accomplished by ubiquitin protein ligases, such as NEDD4-2 (neuronal precursor cell expressed developmentally downregulated-4 type 2).	SIGNOR-253457
Q15796	P36896	0	phosphorylation	up-regulates activity	0.802	ActRIIB, and then partners with a type I receptor, either activin receptor-like kinase 4 (ALK4 or ActRIB) or ALK5 (T²RI), to induce phosphorylation of Smad2/Smad3 and activate a TGF-²-like signaling pathway	SIGNOR-235157
P50613	P10275	1	phosphorylation	down-regulates	0.377	Here, we show that the transcription factor tfiih, via its cdk7 kinase, phosphorylates the androgen receptor (ar) at position ar/s515. Strikingly, this phosphorylation is a key step for an accurate transactivation that includes the cyclic recruitment of the transcription machinery, the mdm2 e3 ligase, the subsequent ubiquitination of ar at the promoter of target genes and its degradation by the proteasome machinery	SIGNOR-170599
Q14774	P18146	1	transcriptional regulation	down-regulates quantity by repression	0.262	In this study, we have identified cell cycle regulatory genes as downstream targets of the homeobox gene HLX in cultured trophoblast cells, namely RB1, MYC, EGR1, CDKN1C, ELK1, CCNB1, and JUN. RB1 and MYC mRNA expression was increased with HLX inactivation, whereas EGR1, CDKN1C, ELK1, CCNB1, and JUN mRNA expression was decreased compared with mock-transfected control cells.	SIGNOR-261621
Q9Y3Z3	P06493	0	phosphorylation	down-regulates	0.492	Cyclin a2/cdk1 phosphorylates samhd1 at the threonine 592 residue both in vitro and in vivo. Phosphorylation of samhd1 thr592 correlates with loss of its ability to restrict hiv-1.	SIGNOR-201913
Q8NG27	Q15910	1	ubiquitination	down-regulates quantity by destabilization	0.488	Biochemical and genetic evidence demonstrates that the MYOD-induced E3 ubiquitin ligase Praja1 (PJA1) is involved in regulating EZH2 levels upon p38α activation. EZH2 premature degradation in proliferating myoblasts is prevented by low levels of PJA1, its cytoplasmic localization and the lower activity towards unphosphorylated EZH2	SIGNOR-255664
P31749	Q96B36	1	phosphorylation	down-regulates activity	0.782	Treatment of these cells with 4-hydroxytamoxifen stimulated the phosphorylation of wt PRAS40 but not the mutant PRAS40 in which Thr-246 was mutated. These results demonstrate that activation of Akt alone is sufficient to induce phosphorylation of PRAS40	SIGNOR-252544
O60216	P53350	0	dephosphorylation	down-regulates quantity by destabilization	0.737	We suspected that the observed enhancement of Scc1's cleavability in the presence of Plk1 might be due to phosphorylation at two sites that are directly adjacent to the cleavage sites, Ser175 and Ser454, which we had found to be phosphorylated in mitosis in vivo (Table 1). We therefore mutated these two residues to alanine, thereby creating mutant Scc1-S175A/S454A (see Figure 1C), and tested the cleavability of this mutant in the absence or presence of Plk1 in vitro. \|Scc1 phosphorylation is dispensable for cohesin dissociation from chromosomes in early mitosis but enhances the cleavability of Scc1 by separase.	SIGNOR-275535
Q16539	P24385	1	phosphorylation	up-regulates	0.426	A large number of cytosolic proteins can be phosphorylated by p38 mapks, including phospholipase a2, the microtubule-associated protein tau, nhe-1, cyclin d1, cdk inhibitors, bcl2 family proteins, growth factor receptors or keratins	SIGNOR-166594
P49841	Q16584	1	phosphorylation	up-regulates activity	0.336	Further, investigation revealed that MLK3 was phosphorylated at two residues Ser789 and Ser793 by GSK3\u03b2 ( xref ).\|When, these two sites on MLK3 were mutated to non-phosphorable Ala, the activation of MLK3 by GSK3\u03b2 was blocked, and neuronal cell death upon NGF withdrawal also prevented ( xref ).	SIGNOR-279615
Q5JTC6	O15169	1	relocalization	up-regulates activity	0.789	Amer1 binds ck1gamma, recruits axin and gsk3beta to the plasma membrane and promotes complex formation between axin and lrp6.	SIGNOR-171886
Q7Z6J0	Q15011	1	ubiquitination	up-regulates activity	0.324	Upon TG induced ER calcium store depletion, POSH promotes Herp lys-63-linked polyubiquitination, which in turn promotes the redistribution of Herp to the ER .\|Upon thapsigargin-induced endoplasmic reticulum calcium store depletion, POSH promotes Herp lys-63-linked polyubiquitination, which in turn promotes the redistribution of Herp to the endoplasmic reticulum .	SIGNOR-278779
Q6ZN44	P17252	0	phosphorylation	down-regulates quantity	0.2	We show that protein interacting with C-kinase 1 (PICK1) recruits activated protein kinase Cα (PKCα) to MycUNC5A at the plasma membrane, stimulating its endocytosis. We identify two PKCα phosphorylation sites at serines 408 and 587, as well as dileucine internalization motifs, which are required for this endocytosis.	SIGNOR-268180
P51812	Q14934	1	phosphorylation	up-regulates	0.385	The results indicated that rsk2 phosphorylated two additional sites at ser289 (peptide 2) and ser344 (peptide 3)rsk2 induced nuclear localization of nfat3. Rsk2 phosphorylated nfat3 in vitro (km=3.559 microm), and activation of nfat3 by rsk2 enhanced the promoter activity of nfat3 downstream target genes in vivo.	SIGNOR-234473
Q8TEW0	O14965	0	phosphorylation	up-regulates	0.35	Aurora a interacts directly with the atypical protein kinase c binding domain of par3 and phosphorylates it at serine 962. The phosphorylation of par3 at serine 962 contributes to its function in the establishment of neuronal polarity.	SIGNOR-188398
P23470	P29353	1	dephosphorylation	down-regulates activity	0.2	PTPRG activation by the P1-WD peptide affected the tyrosine phosphorylation of several signaling molecules. Data analysis identified 31 molecules whose phosphorylation was modified in a statistically significant manner (Table I). inhibition of ABL1, BMX, BTK, DAB1, ITGB1, JAK2, KDR, KIT, LIMK1, MET, PDGFRB, SHC1, and VCL correlates with tyrosine dephosphorylation. In contrast, SRC inhibition correlates with hyperphosphorylation of the inhibitory Tyr530 residue and with dephosphorylation of the activatory Tyr419. Moreover, CDK2 and CTTN inhibition correlates with a hyperphosphorylation of the inhibitory Tyr15 and Tyr470, respectively. In contrast, a subgroup of 13 proteins, including BLNK, DOK2, ERBB2, GRIN2B, INSR, PDGFRA, PRKCD, PXN, STAT1, STAT2, STAT3, STAT5A, and ZAP70, appears to be activated by PTPRG activity.	SIGNOR-254724
P98177	P45983	0	phosphorylation	up-regulates	0.612	Upon treatment of cells with h2o2, the small gtpase ral is activated and this results in a jnk-dependent phosphorylation of foxo4 on threonine 447 and threonine 451. This ral-mediated, jnk-dependent phosphorylation is involved in the nuclear translocation and transcriptional activation of foxo4 after h2o2 treatment.	SIGNOR-130385
P20749	Q9NQC7	0	deubiquitination	down-regulates	0.512	Cyld binds and deubiquitinates bcl-3in cyld+/+ keratinocytes, tpa or uv light triggers the translocation of cyld from the cytoplasm to the perinuclear region, where cyld binds and deubiquitinates bcl-3, thereby preventing nuclear accumulation of bcl-3 and p50/bcl-3- or p52/bcl-3-dependent proliferation.	SIGNOR-146774
P27361	Q9UIG0	1	phosphorylation	up-regulates	0.2	Wstf, a specific component of two chromatin remodeling complexes (swi/snf-type winac and iswi-type wich), was phosphorylated by the stimulation of mapk cascades in vitro and in vivo. Ser-158 residue in the wac (wstf/acf1/cbpq46) domain, located close to the n terminus of wstf, was identified as a major phosphorylation target	SIGNOR-188164
P01106	Q13309	0	ubiquitination	down-regulates quantity	0.736	The F-box protein Skp2 mediates c-Myc ubiquitylation by binding to the MB2 domain	SIGNOR-243548
P19634	Q99558	0	phosphorylation	up-regulates activity	0.307	The Nck-interacting kinase (NIK) phosphorylates the Na+-H+ exchanger NHE1 and regulates NHE1 activation by platelet-derived growth factor.\|We now show that NIK binds to and divergently activates the plasma membrane Na(+)-H(+) exchanger NHE1.	SIGNOR-279632
P06239	O43561	1	phosphorylation	up-regulates	0.758	Evidence of lat as a dual substrate for lck and syk in t lymphocytes.Lat is a linker protein essential for activation of t lymphocytes. Its rapid tyrosine-phosphorylation upon t cell receptor (tcr) stimulation recruits downstream signaling molecules for membrane targeting and activation.	SIGNOR-149182
Q8WY64	P98155	1	ubiquitination	down-regulates quantity by destabilization	0.698	Here we demonstrate that Idol also targets two closely related LDLR family members, VLDLR and ApoE receptor 2 (ApoER2), proteins implicated in both neuronal development and lipid metabolism. Idol triggers ubiquitination of the VLDLR and ApoER2 on their cytoplasmic tails, leading to their degradation.	SIGNOR-271487
P32245	Q5JWF2	1	null	up-regulates activity	0.521	We hypothesize that XLŒ±s may be involved in this regulatory loop by coupling to melanocortin receptors 3 and 4 in the hypothalamus.	SIGNOR-253067
P06241	Q12879	1	phosphorylation	up-regulates activity	0.734	To gain further insight into the roles of Src and Fyn in the phosphorylation and regulation of the NMDA receptor, we have characterized the tyrosine phosphorylation of NR2A and NR2B by exogenous Src and FynIn the case of NR2A, three potential tyrosine phosphorylation sites have been proposed: Tyr1105, Tyr1267 and Tyr1387 (Zheng et al. 1998; Bi et al. 2000), all of which are similarly located in the C-terminal, cytoplasmic domain.	SIGNOR-247151
Q2Q1W2	Q6ZN17	1	polyubiquitination	down-regulates quantity by destabilization	0.527	In cells, TRIM71 negatively regulates Lin28B protein stability by catalyzing polyubiquitination.	SIGNOR-272054
P27694	Q13153	0	phosphorylation	up-regulates activity	0.2	In this article, we found that Ser-135 and Thr-180 of RPA1 are directly phosphorylated by PAK1 in a DOCK7-Rac1/Cdc42-dependent manner.\|We further explored the biological role of PAK1 in replication stress and found that depletion of PAK1 resulted in decreased RPA1 and RPA2 chromatin loading and RPA2 foci formation ( Figure 4I-K ) .	SIGNOR-279378
P01920	Q86YJ5	0	ubiquitination	down-regulates quantity by destabilization	0.2	MARCH9, a member of the RING-CH family of transmembrane E3 ubiquitin ligases, down-regulates CD4, major histocompatibility complex-I (MHC), and ICAM-1 in lymphoid cells. To identify novel MARCH9 substrates, we used high throughput flow cytometry and quantitative mass spectrometry by stable isotope labeling by amino acids in cell culture (SILAC) to determine the differential expression of plasma membrane proteins in a MARCH9-expressing B cell line. This combined approach identified 13 potential new MARCH9 targets.	SIGNOR-271539
P29353	P29376	0	phosphorylation	up-regulates	0.424	Recently, we demonstrated that ltk utilizes shc and irs-1 as two major substrates and while both equally activate the ras pathway, only irs-1 suppresses apoptosis of hematopoietic cells.	SIGNOR-49625
Q9UIG0	P45984	0	phosphorylation	up-regulates	0.2	Wstf, a specific component of two chromatin remodeling complexes (swi/snf-type winac and iswi-type wich), was phosphorylated by the stimulation of mapk cascades in vitro and in vivo. Ser-158 residue in the wac (wstf/acf1/cbpq46) domain, located close to the n terminus of wstf, was identified as a major phosphorylation target	SIGNOR-188168
Q9HCI7	P04637	1	ubiquitination	down-regulates activity	0.37	Here we describe MSL2, a novel E3 ligase for p53 that promotes ubiquitin-dependent cytoplasmic p53 localization. Unlike Mdm2 or most other p53 E3 ligases, MSL2-mediated p53 ubiquitination does not affect the stability of p53. Moreover, the MSL2-mediated effect on p53 is Mdm2-independent. Thus, our study identifies an important ubiquitin-ligase for modulating p53 subcellular localization. MSL2 ubiquitination of p53 is required for p53 cytoplasmic localization.	SIGNOR-271774
Q05655	P17405	1	phosphorylation	up-regulates	0.256	Activation of acid sphingomyelinase by protein kinase cdelta-mediated phosphorylation. Phosphorylation of ser(508) proved to be an indispensable step for asmase activation and membrane translocation in response to pma	SIGNOR-153276
Q05682	P27361	0	phosphorylation	down-regulates	0.478	The actin binding properties of the minimal inhibitory region of caldesmon, residues 750-779, alter upon map kinase phosphorylation of ser-759. This phosphorylation leads to markedly diminished actin affinity.	SIGNOR-86741
P68400	P49736	1	phosphorylation	up-regulates	0.259	In this work, by in vitro kinase reactions and mass spectrometry analysis of the products, we have mapped phosphorylation sites in the n terminus of mcm2 by cdc7, cdk2, cdk1, and ck2	SIGNOR-144004
Q16539	P13726	1	phosphorylation	down-regulates	0.291	We previously showed that the phosphorylation of ser253 within the cytoplasmic domain of human tissue factor (tf) initiates the incorporation and release of this protein into cell-derived microparticles. Furthermore, subsequent phosphorylation of ser258 terminates this process. Our current study has identified p38_ as a major kinase, responsible for the phosphorylation of ser258 within the cytoplasmic domain of tf	SIGNOR-199868
P19525	P40763	1	phosphorylation	up-regulates activity	0.612	Silencing PKR gene expression in HepG2 cells with siRNA reduced STAT3 phosphorylation at Tyr705 and Ser727 (XREF_FIG).\|The results also revealed that PKR activates STAT3, a transcription factor associated with primary liver tumors, which is suggested to promote tumor cell proliferation.	SIGNOR-279613
P14635	A6NLU0	0	ubiquitination	down-regulates quantity by destabilization	0.32	We conclude that, like many RING-finger containing proteins, RFPL4 is an E3 ubiquitin ligase. The specificity of its expression and these interactions suggest that RFPL4 targets cyclin B1 for proteasomal degradation, a key aspect of oocyte cell cycle control during meiosis and the crucial oocyte-to-embryo transition to mitosis.	SIGNOR-271476
P06702	P49715	0	transcriptional regulation	up-regulates quantity by expression	0.227	Among several known transcription factor binding motifs, nuclear protein(s) of VD3-treated HL-60 cells and THP-1 cells bound to the CCAAT/enhancer binding protein (C/EBP)-binding motif that was located in the upstream region of the MRP14 gene (-81), as evidenced by the competitive gel mobility-shift assay.\|Thus, it was concluded that C/EBP alpha and -beta were able to bind to the C/EBP motif, and that C/EBP alpha bound to the motif in THP-1 cells and C/EBP beta bound to that in the VD3-treated HL-60 cells.	SIGNOR-254041
Q8IXJ6	P24941	0	phosphorylation	down-regulates	0.395	We define ser-331 as the site phosphorylated by cyclin e-cdk2, cyclin a-cdk2, and p35-cdk5 both in vitro and in cells. Importantly, phosphorylation at ser-331 inhibits the catalytic activity of sirt2.	SIGNOR-177972
Q96GD4	P25490	1	phosphorylation	up-regulates	0.368	Aurora b kinase phosphorylates yy1 on serine 184 and to a lesser extent serine 180 at the g2/m stage of the cell cycle (fig. 7). We show that yy1 is rapidly dephosphorylated as the cells exit mitosis, likely by pp1. Also, our data indicates that phosphorylation at serine 180 and serine 184 can affect the dna binding activity of yy1	SIGNOR-200079
Q8WWF5	O43353	1	ubiquitination	down-regulates quantity by destabilization	0.2	Collectively, ZNRF4 degrades RIP2 protein by targeting the RIP2CARD domain in an E3-ubiquitin ligase activity dependent manner.\|Here we show that ZNRF4 induces K48-linked ubiquitination of RIP2 and promotes RIP2 degradation.	SIGNOR-278684
Q13424	P29475	1	relocalization	up-regulates	0.558	biochemical studies showed that the N-terminal PDZ domain of nNOS binds to a similar PDZ domain of syntrophin (Fig. 1), a dystrophin-associated protein	SIGNOR-236916
P49841	P56693	1	phosphorylation	down-regulates quantity	0.406	Besides, GSK3\u03b2 phosphorylates SOX10 at CPD domain and facilitates Fbxw7\u03b1-mediated SOX10 degradation.\|Besides, GSK3beta phosphorylates SOX10 at CPD domain and facilitates Fbxw7alpha mediated SOX10 degradation.	SIGNOR-279617
O43524	O00141	0	phosphorylation	down-regulates activity	0.794	We show here that sgk1, like akt, promotes cell survival and that it does so in part by phosphorylating and inactivating fkhrl1. However, sgk and akt display differences with respect to the efficacy with which they phosphorylate the three regulatory sites on fkhrl1. While both kinases can phosphorylate thr-32, sgk displays a marked preference for ser-315 whereas akt favors ser-253.	SIGNOR-236607

P54253

O75582

0

phosphorylation

up-regulates quantity by stabilization

0.26

In summary, the data from the cell based screen, biochemical studies and genetic interactions strongly suggest that MSK1 phosphorylates ATXN1 and regulates its stability.

SIGNOR-279109

O14548

Q99683

0

phosphorylation

up-regulates activity

0.2

Phosphorylation of EB1 by ASK1 promotes the binding of EB1 to CLIP-170 and p150 glued.

SIGNOR-278341

Q9NWF9

Q9NR96

1

ubiquitination

down-regulates quantity by destabilization

0.406

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

SIGNOR-271505

P17252

Q13769

1

phosphorylation

up-regulates

0.327

We conclude m-csf-mediated activation of pkcalpha can potentiate fmip action to initiate survival/differentiation signaling.

SIGNOR-126572

P28482

P16949

1

phosphorylation

down-regulates

0.452

Involved in the regulation of the microtubule (mt) filament system by destabilizing microtubules. Prevents assembly and promotes disassembly of microtubules. The kinases involved in phosphorylating stmn ser-16 and ser-63 include camp-dependent protein kinase (pka) and pak1, whereas stmn ser-25 and ser-38 have been shown to be targets for proline-directed serine/threonine kinases such as cyclin-dependent kinases, erk1/2, and members of the p38 mapk subfamily.

SIGNOR-166686

Q05513

P35222

1

phosphorylation

down-regulates quantity by destabilization

0.599

Yap and β-catenin are direct substrates of PKCζ. Similar MS/MS analysis to map the sites phosphorylated in β-catenin by PKCζ identified S45 and several sites of low abundance that included S552 and S675 (Figure S3C).

SIGNOR-276880

Q07820

Q7Z6Z7

0

ubiquitination

down-regulates quantity by destabilization

0.502

Mule was identified as Mcl-1 ubiquitin ligase E3 to promote Mcl-1 degradation via the proteasomal pathway [46]. We found that knockdown of Mule (Fig. 4C) but not β-TRCP or FBXW7 (data not shown) prevented Mcl-1 downregulation caused by PKCη depletion.

SIGNOR-261909

Q07820

Q13627

0

phosphorylation

up-regulates quantity

0.2

Furthermore, DYRK1A likely directly bound and phosphorylated Mcl-1, thereby enhancing Mcl-1 protein stability and contributing to the development of acquired resistance to Bcl-2 inhibitors.|DYRK1A upregulates Mcl-1 expression in NSCLC cells.|We demonstrated that DYRK1A suppression by siRNA or harmine decreased the phosphorylation of Mcl-1 at Ser159/Thr163.

SIGNOR-279704

P01112

P12931

0

phosphorylation

down-regulates activity

0.775

Src binds to and phosphorylates GTP-, but not GDP-, loaded Ras on a conserved Y32 residue within the switch I region in vitro and that in vivo, Ras-Y32 phosphorylation markedly reduces the binding to effector Raf and concomitantly increases binding to GTPase-activating proteins and the rate of GTP hydrolysis

SIGNOR-252093

Q66K74

Q13618

0

ubiquitination

down-regulates quantity

0.242

Gigaxonin is the substrate-specific adaptor for a new Cul3-E3-ubiquitin ligase family that promotes the proteasome dependent degradation of its partners MAP1B, MAP8 and tubulin cofactor B.

SIGNOR-268947

P17947

P49841

0

phosphorylation

down-regulates quantity by destabilization

0.2

We demonstrate that GSK3β phosphorylates PU.1 at Ser41 and Ser140 leading to its recognition and subsequent ubiquitin-mediated degradation by E3 ubiquitin ligase FBW7.

SIGNOR-277541

P43405

P29350

0

dephosphorylation

down-regulates

0.737

We propose that shp1 can dephosphorylate sites in zap-70 and syk that are involved in coupling these kinases to downstream signaling cascades, including erk2 and elements of the il-2 gene.

SIGNOR-70234

Q9H3R0

P68431

1

demethylation

down-regulates activity

0.2

As one member of the Jumonji-C histone demethylase family, JMJD2C has the ability to demethylate tri- or di-methylated histone 3 and 2 in either K9 (lysine residue 9) or K36 (lysine residue 36) sites by an oxidative reaction, thereby affecting heterochromatin formation, genomic imprinting, X-chromosome inactivation, and transcriptional regulation of genes.JMJD2C has been proved to be a demethylase for H3K9 methylation, in the manner of catalyzing the demethylation of H3K9me3/me2 (the known repressive markers of gene regulation), a histone mark found in heterochromatin associated with euchromatic transcriptional silencing and heterochromatin formation

SIGNOR-263864

Q96QZ7

Q15418

0

phosphorylation

up-regulates activity

0.286

We report herein that p90RSK associates with MAGI1 in ECs and executes 2 independently regulated PTMs of MAGI1: S741 phosphorylation and K931 deSUMOylation. MAGI1-S741 phosphorylation is vital for Rap1 activation.

SIGNOR-273837

P27361

P17655

1

phosphorylation

up-regulates

0.565

Epidermal growth factor activates m-calpain (calpain ii), at least in part, by extracellular signal-regulated kinase-mediated phosphorylation.We now show that erk directly phosphorylates and activates m-calpain both in vitro and in vivo. We identified serine 50 as required for epidermal growth factor (egf)-induced calpain activation in vitro and in vivo.

SIGNOR-123083

Q96A00

Q05513

0

phosphorylation

up-regulates activity

0.277

A major kinase for GPCR‐induced CPI‐17 phosphorylation is PKC which is activated by the PLCbeta‐produced signaling messenger diacylglycerol (DAG). It phosphorylates CPI‐17 at Thr38 residue that directly docks at the active site of MLCP, thereby inhibiting its activity and promoting an increase of phosphorylation of myosin and of other MLCP.

SIGNOR-249261

P42263

Q5JU85

0

relocalization

up-regulates quantity

0.2

BRAG1 increases the synaptic recycling pool of AMPARs.these data suggest that the BRAG1 enhancement of AMPAR transmission is mediated by the increased expression of the recycling pool of synaptic GluA2/3 receptors.

SIGNOR-264914

P48729

Q9UKV8

1

phosphorylation

down-regulates activity

0.369

Our experiments demonstrated that target engagement by AGO2 stimulates its hierarchical, multi-site phosphorylation by CSNK1A1 on a series of highly conserved residues (S824-S834).Although this impairs target binding, dephosphorylation by ANKRD52-PPP6C allows AGO2 to engage new targets. Inactivation of this cycle strongly inhibits global miRNA-mediated repression.

SIGNOR-276510

Q13887

P04150

0

transcriptional regulation

up-regulates quantity by expression

0.292

We show that in addition, DEX-bound GR directly promotes the expression of adipogenic TFs, including C/EBPβ, Klf5, Klf9, and C/EBPα

SIGNOR-256118

Q9NZQ7

Q8TCJ2

0

glycosylation

up-regulates quantity by stabilization

0.2

Together, these results support a notion that the two STT3 isoforms regulate EMT-mediated PD-L1 induction through PD-L1 protein N-glycosylation and stabilization.

SIGNOR-274976

P28482

Q7LDG7

1

phosphorylation

down-regulates activity

0.396

ERK2 phosphorylates RasGRP2 at Ser394 located in the linker region implicated in its autoinhibition.

SIGNOR-279537

P53350

O95425

1

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

P19174

Q96EB6

0

deacetylation

up-regulates activity

0.2

The histone acetyltransferase GCN5 (general control non-repressed protein 5) acetylates PGC-1alpha and suppresses its transcriptional activity, whereas sirtuin 1 deacetylates and activates PGC-1alpha.

SIGNOR-275499

P20823

O60656

1

transcriptional regulation

up-regulates quantity by expression

0.267

Using gel shift and functional assays, HNF1alpha was demonstrated to bind to and activate the UGT1A8, -1A9, and -1A10 promoters. In contrast, Cdx2 bound to and activated the UGT1A8 and -1A10 promoters but could not activate the UGT1A9 promoter.

SIGNOR-253973

Q16891

P17612

0

phosphorylation

down-regulates activity

0.2

PKA directly phosphorylated the Ser528 residue of MIC60. Phosphorylation of MIC60 Interrupts Parkin Recruitment and Formation of the MICOS Complex

SIGNOR-266302

Q96P20

O95376

0

ubiquitination

up-regulates activity

0.444

ARIH2 can ubiquitinate NLRP3 via the NACHT domain of NLRP3, and the RING2 domain of ARIH2 is required for NLRP3 ubiquitination 65.|Overexpression of ARIH2 promotes NLRP3 ubiquitination and inhibits NLRP3 inflammasome activation 65.

SIGNOR-278686

P61586

Q9NR80

0

guanine nucleotide exchange factor

up-regulates activity

0.667

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-260531

Q8N6T7

P31749

0

phosphorylation

down-regulates activity

0.532

AKT1 interacts with and phosphorylates SIRT6 on Ser 338.|Because AKT1 suppresses SIRT6 protein abundance by decreasing its stability, we investigated whether MDM2 is involved in this process.

SIGNOR-278465

O15084

Q13557

0

phosphorylation

down-regulates activity

0.2

We provide evidence for a dual kinase-mediated regulation of the PITK holoenzyme whereby PITK phosphorylation at S1017 is catalyzed by calcium/calmodulin-dependent kinase II-delta (CaMKIIdelta), promoting the subsequent phosphorylation of S1013 by glycogen synthase kinase-3 (GSK3) in vitro.|the phosphorylation of PITK at these specific residues altered PP1 binding and subsequent PITK-directed dephosphorylation of hnRNP K

SIGNOR-264793

Q9UKW4

P12931

0

phosphorylation

up-regulates

0.325

Activation of rac1 and the exchange factor vav3 are involved in npm-alk signaling in anaplastic large cell lymphomas.

SIGNOR-159240

P31751

O60343

1

phosphorylation

down-regulates activity

0.642

AKT2 phosphorylation blocks AS160 function enhancing GLUT4 intracellular vesicular transport, and as such promotes glucose uptake following insulin release .|Notable mechanisms promoting this involves AKT2 mediated phosphorylation of the Rab-GTPase-activating protein TBC1D4, also known as AS160.

SIGNOR-280179

Q8NHV4

P06493

0

phosphorylation

up-regulates activity

0.585

Here we report that the function of Nedd1 is regulated by Cdk1 and Plk1. During mitosis, Nedd1 is firstly phosphorylated at T550 by Cdk1, which creates a binding site for the polo-box domain of Plk1. Then, Nedd1 is further phosphorylated by Plk1 at four sites: T382, S397, S637 and S426. The sequential phosphorylation of Nedd1 by Cdk1 and Plk1 promotes its interaction with gamma-tubulin for targeting the gammaTuRC to the centrosome and is important for spindle formation.

SIGNOR-272973

P30304

P11802

1

dephosphorylation

up-regulates activity

0.705

Invalidation of CDK4 has no impact by itself on the cell proliferation, but invalidation of CDC25A prevents the dephosphorylation of CDK6 (Y24) and CDK4 (Y17) residues, and impedes their association with CCNDs.

SIGNOR-267568

O43318

Q9Y572

1

phosphorylation

up-regulates activity

0.2

Collectively, TAK1 activates RIPK3, RIPK3 activates TAK1, and RIPK1 activates RIPK3 and facilitates interaction between TAK1 and RIPK3.|We found that prolonged and hyperactivation of TAK1 induced phosphorylation and activation of RIPK3, leading to necrosis without caspase activation.

SIGNOR-279634

Q16665

Q9H4B4

0

phosphorylation

down-regulates

0.348

Polo-like kinase 3 functions as a tumor suppressor and is a negative regulator of hypoxia-inducible factor-1 alpha under hypoxic conditionsplk3 can potentially inhibit hif-1_ by physical interaction and direct phosphorylation

SIGNOR-178743

Q86WV6

P35813

0

dephosphorylation

down-regulates activity

0.2

Collectively, our findings suggest that the overexpression of PPM1A antagonizes the STING- and TBK1-induced type I interferon signaling pathway.|First, PPM1A directly dephosphorylated STING, likely via its S358 site (Figs.|Moreover, our study demonstrates that while TBK1 enhances STING aggregation in a kinase activity-dependent manner, PPM1A suppresses STING aggregation by dephosphorylating both STING and TBK1.

SIGNOR-276958

Q14247

P11362

0

phosphorylation

down-regulates

0.313

Cortactin, which is an actin-binding protein that also plays a role in actin cytoskeleton dynamics (45), was phosphorylated on tyr-446 in our assay (by fgfr1).Phosphorylation of these residues attenuates the f-actin cross-linking activity

SIGNOR-98618

P29353

Q05397

0

phosphorylation

up-regulates activity

0.674

In vitro, FAK directly phosphorylated Shc Tyr-317 to promote Grb2 binding. FAK can associate and directly phosphorylate Shc at Tyr-317 to promote Grb2 binding and low-level signaling to ERK2.

SIGNOR-259854

Q16539

Q13950

1

phosphorylation

up-regulates activity

0.367

Mechanistic analysis revealed that the TAK1–MKK3/6–p38 MAPK axis phosphorylated Runx2, promoting its association with the coactivator CREB-binding protein (CBP), which was required to regulate osteoblast genetic programs. These findings reveal an in vivo function for p38β and establish that MAPK signaling is essential for bone formation in vivo.

SIGNOR-255777

Q9Y6Q9

P06493

0

phosphorylation

down-regulates

0.368

We demonstrate that aib1 is phosphorylated on ser728 and ser867 by cdk1/cyclin b at the onset of mitosis and remains phosphorylated until exit from m phase.

SIGNOR-195233

Q14694

P04637

1

deubiquitination

up-regulates quantity by stabilization

0.662

Since USP10 is known as a deubiquitinating protease of p53 (Yuan et al., 2010), inhibition of USP10 by spautin-1 may promote the degradation of p53.

SIGNOR-260297

Q05655

P40189

1

phosphorylation

up-regulates activity

0.334

Finally, we identified Thr-890, a putative PKC phosphorylation site on gp130, to be critical for the effect of PKCdelta. Our data indicate that PKCdelta plays important regulatory roles in IL-6 signaling.

SIGNOR-249177

O43280

P06493

0

phosphorylation

up-regulates activity

0.268

Ewald et al. reported that at the G1/S transition, cyclin-dependent kinase 1 (CDK1) phosphorylates and activates the neutral trehalase (NTH1) to funnel trehalose into glycolysis (Ewald et al. xref ).

SIGNOR-280206

Q05086

P04637

1

ubiquitination

down-regulates quantity

0.681

E6-AP also directly ubiquitylated p53 in an in vitro ubiquitylation assay.|Our result suggests that E6-AP not only enhances the degradation of p53 but also regulates the neuronal cell growth.

SIGNOR-278681

Q00535

Q9UD71

1

phosphorylation

up-regulates activity

0.777

We find that DARPP-32 is converted into an inhibitor of PKA when phosphorylated at threonine 75 by cyclin-dependent kinase 5 (Cdk5). Cdk5 phosphorylates DARPP-32 in vitro and in intact brain cells. Phospho-Thr 75 DARPP-32 inhibits PKA in vitro by a competitive mechanism.

SIGNOR-250671

O14672

P12830

1

cleavage

up-regulates activity

0.548

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-259846

Q14693

P12931

0

phosphorylation

up-regulates activity

0.2

Obesity-associated microenvironmental factors and other Src-activating growth factors, including the epidermal growth factor, activate Src and promote Src-mediated lipin-1 phosphorylation on Tyr398, Tyr413 and Tyr795 residues. The tyrosine phosphorylation of lipin-1 markedly increases its PAP activity, accelerating the synthesis of glycerophospholipids and triglyceride.

SIGNOR-277291

P35236

Q05655

0

phosphorylation

up-regulates activity

0.2

HePTP is phosphorylated by PKC isozymes at Ser-225 in vitro. While all isozymes phosphorylated Ser-225 predominantly and Ser-113 to a lesser extent (Fig. (Fig.5),5), they differed strikingly in how much 32P they incorporated into HePTP during the 30-min assay. PKC θ was the most efficient, while PKC ζ and PKC μ were clearly less potent; PKC δ, ɛ, and η were quite inefficient.

SIGNOR-276048

P78504

O76050

0

ubiquitination

down-regulates quantity by destabilization

0.707

We find that NEDD4 targets an RNA-binding protein, NANOS2, in spermatogonia to destabilize it, leading to cell differentiation.|Jagged1 is also regulated by the E3 ligase Neuralized-like1 (Neurl1), which induces the monoubiquitination of membrane tethered Jagged1 in the C-terminal region.

SIGNOR-278772

P04637

O43683

0

phosphorylation

up-regulates activity

0.484

In addition, purified Bub1 directly phosphorylates p53 on Ser-37 in vitro , possibly inducing cellular senescence [ xref ].|Studies have shown that depletion and inhibition of Aurora A, Aurora B, Plk1, or Bub1 induces cellular senescence or cell death in a p53 dependent or -independent but p73 dependent manner in many different cell types , - ].

SIGNOR-280199

P29350

P35222

1

dephosphorylation

down-regulates quantity by destabilization

0.558

Because SHP-1 can dephosphorylate residues Y86 and Y654 on the \u03b2-catenin protein, these residues were therefore mutated into phenylalanine and the transcriptional activity of the subsequent \u03b2-catenin mutants analyzed: \u03b2-catenin/Y86F, \u03b2-catenin/Y654F and \u03b2-catenin/Y86F/Y654F. As shown in Fig.\u00a03 B, the mutants \u03b2-catenin/Y86F, \u03b2-catenin/Y654F and \u03b2-catenin/Y86F/Y654F had a significantly reduced transcriptional activity in comparison to wild-type \u03b2-catenin.|SHP-1 inhibits \u03b2-catenin function by inducing its degradation and interfering with its association with TATA-binding protein.

SIGNOR-277014

Q9P286

O95831

1

phosphorylation

down-regulates activity

0.2

Our results show that PAK5 can phosphorylate Thr-281 of AIF, which is included in its NLS1 sequence.|These results suggested that PAK5 inhibited AIF from entering the nucleus through phosphorylation of AIF T281 site, thus inhibiting cell apoptosis.

SIGNOR-279085

Q9BYT3

P32754

1

phosphorylation

down-regulates quantity by destabilization

0.2

Decreased expression of 4-hydroxyphenylpyruvic acid dioxygenase (HPD), a key enzyme for tyrosine metabolism, is a cause of human tyrosinemia. However, the regulation of HPD expression remains largely unknown. Here, we demonstrate that molecular chaperone TTC36, which is highly expressed in liver, is associated with HPD and reduces the binding of protein kinase STK33 to HPD, thereby inhibiting STK33-mediated HPD T382 phosphorylation. The reduction of HPD T382 phosphorylation results in impaired recruitment of FHA domain-containing PELI1 and PELI1-mediated HPD polyubiquitylation and degradation.

SIGNOR-272958

Q09472

P84022

1

acetylation

up-regulates quantity by stabilization

0.736

Smad proteins are crucial for the intracellular signaling of transforming growth factor-beta (TGF-beta). Upon their receptor-induced activation, Smad proteins are phosphorylated and translocated to the nucleus to activate the transcription of a select set of target genes. Here, we show that the co-activator p300/CBP bound and acetylated Smad3 as well as Smad2 in vivo, and that the acetylation was stimulated by TGF-beta.A major acetylation site of Smad3 by p300/CBP is Lys-378 in the MH2 domain (Smad3C) known to be critical for the regulation of transcriptional activity.

SIGNOR-260431

O00303

P46531

1

deubiquitination

up-regulates

0.421

The activated form of notch needs to be deubiquitinated before being processed by the gamma-secretase activity and entering the nucleus, where it fulfills its transcriptional function. The enzyme accounting for this deubiquitinase activity is eif3f, known so far as a translation initiation factor.

SIGNOR-170158

P62140

P35240

1

dephosphorylation

up-regulates

0.378

When serine 518 is dephosphorylated by the myosin phosphatase mypt-1-pp1?, The tumor suppressor function of merlin is activated, inhibiting the ras signaling pathway and leading to growth arrest

SIGNOR-159836

P35498

Q96PU5

0

ubiquitination

down-regulates quantity by destabilization

0.292

The control of Nav density at the cell membrane is crucial to ensuring normal neuronal excitability. Navs are subject to posttranslational modifications that may influence their cell membrane availability. Ubiquitylation is a key process that orchestrates the internalization and subsequent degradation or recycling of Navs. This is accomplished by ubiquitin protein ligases, such as NEDD4-2 (neuronal precursor cell expressed developmentally downregulated-4 type 2).

SIGNOR-253457

Q15796

P36896

0

phosphorylation

up-regulates activity

0.802

ActRIIB, and then partners with a type I receptor, either activin receptor-like kinase 4 (ALK4 or ActRIB) or ALK5 (T²RI), to induce phosphorylation of Smad2/Smad3 and activate a TGF-²-like signaling pathway

SIGNOR-235157

P50613

P10275

1

phosphorylation

down-regulates

0.377

Here, we show that the transcription factor tfiih, via its cdk7 kinase, phosphorylates the androgen receptor (ar) at position ar/s515. Strikingly, this phosphorylation is a key step for an accurate transactivation that includes the cyclic recruitment of the transcription machinery, the mdm2 e3 ligase, the subsequent ubiquitination of ar at the promoter of target genes and its degradation by the proteasome machinery

SIGNOR-170599

Q14774

P18146

1

transcriptional regulation

down-regulates quantity by repression

0.262

In this study, we have identified cell cycle regulatory genes as downstream targets of the homeobox gene HLX in cultured trophoblast cells, namely RB1, MYC, EGR1, CDKN1C, ELK1, CCNB1, and JUN. RB1 and MYC mRNA expression was increased with HLX inactivation, whereas EGR1, CDKN1C, ELK1, CCNB1, and JUN mRNA expression was decreased compared with mock-transfected control cells.

SIGNOR-261621

Q9Y3Z3

P06493

0

phosphorylation

down-regulates

0.492

Cyclin a2/cdk1 phosphorylates samhd1 at the threonine 592 residue both in vitro and in vivo. Phosphorylation of samhd1 thr592 correlates with loss of its ability to restrict hiv-1.

SIGNOR-201913

Q8NG27

Q15910

1

ubiquitination

down-regulates quantity by destabilization

0.488

Biochemical and genetic evidence demonstrates that the MYOD-induced E3 ubiquitin ligase Praja1 (PJA1) is involved in regulating EZH2 levels upon p38α activation. EZH2 premature degradation in proliferating myoblasts is prevented by low levels of PJA1, its cytoplasmic localization and the lower activity towards unphosphorylated EZH2

SIGNOR-255664

P31749

Q96B36

1

phosphorylation

down-regulates activity

0.782

Treatment of these cells with 4-hydroxytamoxifen stimulated the phosphorylation of wt PRAS40 but not the mutant PRAS40 in which Thr-246 was mutated. These results demonstrate that activation of Akt alone is sufficient to induce phosphorylation of PRAS40

SIGNOR-252544

O60216

P53350

0

dephosphorylation

down-regulates quantity by destabilization

0.737

We suspected that the observed enhancement of Scc1's cleavability in the presence of Plk1 might be due to phosphorylation at two sites that are directly adjacent to the cleavage sites, Ser175 and Ser454, which we had found to be phosphorylated in mitosis in vivo (Table 1). We therefore mutated these two residues to alanine, thereby creating mutant Scc1-S175A/S454A (see Figure 1C), and tested the cleavability of this mutant in the absence or presence of Plk1 in vitro. |Scc1 phosphorylation is dispensable for cohesin dissociation from chromosomes in early mitosis but enhances the cleavability of Scc1 by separase.

SIGNOR-275535

Q16539

P24385

1

phosphorylation

up-regulates

0.426

A large number of cytosolic proteins can be phosphorylated by p38 mapks, including phospholipase a2, the microtubule-associated protein tau, nhe-1, cyclin d1, cdk inhibitors, bcl2 family proteins, growth factor receptors or keratins

SIGNOR-166594

P49841

Q16584

1

phosphorylation

up-regulates activity

0.336

Further, investigation revealed that MLK3 was phosphorylated at two residues Ser789 and Ser793 by GSK3\u03b2 ( xref ).|When, these two sites on MLK3 were mutated to non-phosphorable Ala, the activation of MLK3 by GSK3\u03b2 was blocked, and neuronal cell death upon NGF withdrawal also prevented ( xref ).

SIGNOR-279615

Q5JTC6

O15169

1

relocalization

up-regulates activity

0.789

Amer1 binds ck1gamma, recruits axin and gsk3beta to the plasma membrane and promotes complex formation between axin and lrp6.

SIGNOR-171886

Q7Z6J0

Q15011

1

ubiquitination

up-regulates activity

0.324

Upon TG induced ER calcium store depletion, POSH promotes Herp lys-63-linked polyubiquitination, which in turn promotes the redistribution of Herp to the ER .|Upon thapsigargin-induced endoplasmic reticulum calcium store depletion, POSH promotes Herp lys-63-linked polyubiquitination, which in turn promotes the redistribution of Herp to the endoplasmic reticulum .

SIGNOR-278779

Q6ZN44

P17252

0

phosphorylation

down-regulates quantity

0.2

We show that protein interacting with C-kinase 1 (PICK1) recruits activated protein kinase Cα (PKCα) to MycUNC5A at the plasma membrane, stimulating its endocytosis. We identify two PKCα phosphorylation sites at serines 408 and 587, as well as dileucine internalization motifs, which are required for this endocytosis.

SIGNOR-268180

P51812

Q14934

1

phosphorylation

up-regulates

0.385

The results indicated that rsk2 phosphorylated two additional sites at ser289 (peptide 2) and ser344 (peptide 3)rsk2 induced nuclear localization of nfat3. Rsk2 phosphorylated nfat3 in vitro (km=3.559 microm), and activation of nfat3 by rsk2 enhanced the promoter activity of nfat3 downstream target genes in vivo.

SIGNOR-234473

Q8TEW0

O14965

0

phosphorylation

up-regulates

0.35

Aurora a interacts directly with the atypical protein kinase c binding domain of par3 and phosphorylates it at serine 962. The phosphorylation of par3 at serine 962 contributes to its function in the establishment of neuronal polarity.

SIGNOR-188398

P23470

P29353

1

dephosphorylation

down-regulates activity

0.2

PTPRG activation by the P1-WD peptide affected the tyrosine phosphorylation of several signaling molecules. Data analysis identified 31 molecules whose phosphorylation was modified in a statistically significant manner (Table I). inhibition of ABL1, BMX, BTK, DAB1, ITGB1, JAK2, KDR, KIT, LIMK1, MET, PDGFRB, SHC1, and VCL correlates with tyrosine dephosphorylation. In contrast, SRC inhibition correlates with hyperphosphorylation of the inhibitory Tyr530 residue and with dephosphorylation of the activatory Tyr419. Moreover, CDK2 and CTTN inhibition correlates with a hyperphosphorylation of the inhibitory Tyr15 and Tyr470, respectively. In contrast, a subgroup of 13 proteins, including BLNK, DOK2, ERBB2, GRIN2B, INSR, PDGFRA, PRKCD, PXN, STAT1, STAT2, STAT3, STAT5A, and ZAP70, appears to be activated by PTPRG activity.

SIGNOR-254724

P98177

P45983

0

phosphorylation

up-regulates

0.612

Upon treatment of cells with h2o2, the small gtpase ral is activated and this results in a jnk-dependent phosphorylation of foxo4 on threonine 447 and threonine 451. This ral-mediated, jnk-dependent phosphorylation is involved in the nuclear translocation and transcriptional activation of foxo4 after h2o2 treatment.

SIGNOR-130385

P20749

Q9NQC7

0

deubiquitination

down-regulates

0.512

Cyld binds and deubiquitinates bcl-3in cyld+/+ keratinocytes, tpa or uv light triggers the translocation of cyld from the cytoplasm to the perinuclear region, where cyld binds and deubiquitinates bcl-3, thereby preventing nuclear accumulation of bcl-3 and p50/bcl-3- or p52/bcl-3-dependent proliferation.

SIGNOR-146774

P27361

Q9UIG0

1

phosphorylation

up-regulates

0.2

Wstf, a specific component of two chromatin remodeling complexes (swi/snf-type winac and iswi-type wich), was phosphorylated by the stimulation of mapk cascades in vitro and in vivo. Ser-158 residue in the wac (wstf/acf1/cbpq46) domain, located close to the n terminus of wstf, was identified as a major phosphorylation target

SIGNOR-188164

P01106

Q13309

0

ubiquitination

down-regulates quantity

0.736

The F-box protein Skp2 mediates c-Myc ubiquitylation by binding to the MB2 domain

SIGNOR-243548

P19634

Q99558

0

phosphorylation

up-regulates activity

0.307

The Nck-interacting kinase (NIK) phosphorylates the Na+-H+ exchanger NHE1 and regulates NHE1 activation by platelet-derived growth factor.|We now show that NIK binds to and divergently activates the plasma membrane Na(+)-H(+) exchanger NHE1.

SIGNOR-279632

P06239

O43561

1

phosphorylation

up-regulates

0.758

Evidence of lat as a dual substrate for lck and syk in t lymphocytes.Lat is a linker protein essential for activation of t lymphocytes. Its rapid tyrosine-phosphorylation upon t cell receptor (tcr) stimulation recruits downstream signaling molecules for membrane targeting and activation.

SIGNOR-149182

Q8WY64

P98155

1

ubiquitination

down-regulates quantity by destabilization

0.698

Here we demonstrate that Idol also targets two closely related LDLR family members, VLDLR and ApoE receptor 2 (ApoER2), proteins implicated in both neuronal development and lipid metabolism. Idol triggers ubiquitination of the VLDLR and ApoER2 on their cytoplasmic tails, leading to their degradation.

SIGNOR-271487

P32245

Q5JWF2

1

null

up-regulates activity

0.521

We hypothesize that XLŒ±s may be involved in this regulatory loop by coupling to melanocortin receptors 3 and 4 in the hypothalamus.

SIGNOR-253067

P06241

Q12879

1

phosphorylation

up-regulates activity

0.734

To gain further insight into the roles of Src and Fyn in the phosphorylation and regulation of the NMDA receptor, we have characterized the tyrosine phosphorylation of NR2A and NR2B by exogenous Src and FynIn the case of NR2A, three potential tyrosine phosphorylation sites have been proposed: Tyr1105, Tyr1267 and Tyr1387 (Zheng et al. 1998; Bi et al. 2000), all of which are similarly located in the C-terminal, cytoplasmic domain.

SIGNOR-247151

Q2Q1W2

Q6ZN17

1

polyubiquitination

down-regulates quantity by destabilization

0.527

In cells, TRIM71 negatively regulates Lin28B protein stability by catalyzing polyubiquitination.

SIGNOR-272054

P27694

Q13153

0

phosphorylation

up-regulates activity

0.2

In this article, we found that Ser-135 and Thr-180 of RPA1 are directly phosphorylated by PAK1 in a DOCK7-Rac1/Cdc42-dependent manner.|We further explored the biological role of PAK1 in replication stress and found that depletion of PAK1 resulted in decreased RPA1 and RPA2 chromatin loading and RPA2 foci formation ( Figure 4I-K ) .

SIGNOR-279378

P01920

Q86YJ5

0

ubiquitination

down-regulates quantity by destabilization

0.2

MARCH9, a member of the RING-CH family of transmembrane E3 ubiquitin ligases, down-regulates CD4, major histocompatibility complex-I (MHC), and ICAM-1 in lymphoid cells. To identify novel MARCH9 substrates, we used high throughput flow cytometry and quantitative mass spectrometry by stable isotope labeling by amino acids in cell culture (SILAC) to determine the differential expression of plasma membrane proteins in a MARCH9-expressing B cell line. This combined approach identified 13 potential new MARCH9 targets.

SIGNOR-271539

P29353

P29376

0

phosphorylation

up-regulates

0.424

Recently, we demonstrated that ltk utilizes shc and irs-1 as two major substrates and while both equally activate the ras pathway, only irs-1 suppresses apoptosis of hematopoietic cells.

SIGNOR-49625

Q9UIG0

P45984

0

phosphorylation

up-regulates

0.2

Wstf, a specific component of two chromatin remodeling complexes (swi/snf-type winac and iswi-type wich), was phosphorylated by the stimulation of mapk cascades in vitro and in vivo. Ser-158 residue in the wac (wstf/acf1/cbpq46) domain, located close to the n terminus of wstf, was identified as a major phosphorylation target

SIGNOR-188168

Q9HCI7

P04637

1

ubiquitination

down-regulates activity

0.37

Here we describe MSL2, a novel E3 ligase for p53 that promotes ubiquitin-dependent cytoplasmic p53 localization. Unlike Mdm2 or most other p53 E3 ligases, MSL2-mediated p53 ubiquitination does not affect the stability of p53. Moreover, the MSL2-mediated effect on p53 is Mdm2-independent. Thus, our study identifies an important ubiquitin-ligase for modulating p53 subcellular localization. MSL2 ubiquitination of p53 is required for p53 cytoplasmic localization.

SIGNOR-271774

Q05655

P17405

1

phosphorylation

up-regulates

0.256

Activation of acid sphingomyelinase by protein kinase cdelta-mediated phosphorylation. Phosphorylation of ser(508) proved to be an indispensable step for asmase activation and membrane translocation in response to pma

SIGNOR-153276

Q05682

P27361

0

phosphorylation

down-regulates

0.478

The actin binding properties of the minimal inhibitory region of caldesmon, residues 750-779, alter upon map kinase phosphorylation of ser-759. This phosphorylation leads to markedly diminished actin affinity.

SIGNOR-86741

P68400

P49736

1

phosphorylation

up-regulates

0.259

In this work, by in vitro kinase reactions and mass spectrometry analysis of the products, we have mapped phosphorylation sites in the n terminus of mcm2 by cdc7, cdk2, cdk1, and ck2

SIGNOR-144004

Q16539

P13726

1

phosphorylation

down-regulates

0.291

We previously showed that the phosphorylation of ser253 within the cytoplasmic domain of human tissue factor (tf) initiates the incorporation and release of this protein into cell-derived microparticles. Furthermore, subsequent phosphorylation of ser258 terminates this process. Our current study has identified p38_ as a major kinase, responsible for the phosphorylation of ser258 within the cytoplasmic domain of tf

SIGNOR-199868

P19525

P40763

1

phosphorylation

up-regulates activity

0.612

Silencing PKR gene expression in HepG2 cells with siRNA reduced STAT3 phosphorylation at Tyr705 and Ser727 (XREF_FIG).|The results also revealed that PKR activates STAT3, a transcription factor associated with primary liver tumors, which is suggested to promote tumor cell proliferation.

SIGNOR-279613

P14635

A6NLU0

0

ubiquitination

down-regulates quantity by destabilization

0.32

We conclude that, like many RING-finger containing proteins, RFPL4 is an E3 ubiquitin ligase. The specificity of its expression and these interactions suggest that RFPL4 targets cyclin B1 for proteasomal degradation, a key aspect of oocyte cell cycle control during meiosis and the crucial oocyte-to-embryo transition to mitosis.

SIGNOR-271476

P06702

P49715

0

transcriptional regulation

up-regulates quantity by expression

0.227

Among several known transcription factor binding motifs, nuclear protein(s) of VD3-treated HL-60 cells and THP-1 cells bound to the CCAAT/enhancer binding protein (C/EBP)-binding motif that was located in the upstream region of the MRP14 gene (-81), as evidenced by the competitive gel mobility-shift assay.|Thus, it was concluded that C/EBP alpha and -beta were able to bind to the C/EBP motif, and that C/EBP alpha bound to the motif in THP-1 cells and C/EBP beta bound to that in the VD3-treated HL-60 cells.

SIGNOR-254041

Q8IXJ6

P24941

0

phosphorylation

down-regulates

0.395

We define ser-331 as the site phosphorylated by cyclin e-cdk2, cyclin a-cdk2, and p35-cdk5 both in vitro and in cells. Importantly, phosphorylation at ser-331 inhibits the catalytic activity of sirt2.

SIGNOR-177972

Q96GD4

P25490

1

phosphorylation

up-regulates

0.368

Aurora b kinase phosphorylates yy1 on serine 184 and to a lesser extent serine 180 at the g2/m stage of the cell cycle (fig. 7). We show that yy1 is rapidly dephosphorylated as the cells exit mitosis, likely by pp1. Also, our data indicates that phosphorylation at serine 180 and serine 184 can affect the dna binding activity of yy1

SIGNOR-200079

Q8WWF5

O43353

1

ubiquitination

down-regulates quantity by destabilization

0.2

Collectively, ZNRF4 degrades RIP2 protein by targeting the RIP2CARD domain in an E3-ubiquitin ligase activity dependent manner.|Here we show that ZNRF4 induces K48-linked ubiquitination of RIP2 and promotes RIP2 degradation.

SIGNOR-278684

Q13424

P29475

1

relocalization

up-regulates

0.558

biochemical studies showed that the N-terminal PDZ domain of nNOS binds to a similar PDZ domain of syntrophin (Fig. 1), a dystrophin-associated protein

SIGNOR-236916

P49841

P56693

1

phosphorylation

down-regulates quantity

0.406

Besides, GSK3\u03b2 phosphorylates SOX10 at CPD domain and facilitates Fbxw7\u03b1-mediated SOX10 degradation.|Besides, GSK3beta phosphorylates SOX10 at CPD domain and facilitates Fbxw7alpha mediated SOX10 degradation.

SIGNOR-279617

O43524

O00141

0

phosphorylation

down-regulates activity

0.794

We show here that sgk1, like akt, promotes cell survival and that it does so in part by phosphorylating and inactivating fkhrl1. However, sgk and akt display differences with respect to the efficacy with which they phosphorylate the three regulatory sites on fkhrl1. While both kinases can phosphorylate thr-32, sgk displays a marked preference for ser-315 whereas akt favors ser-253.

SIGNOR-236607