GleghornLab/Signor_2class · Datasets at Hugging Face

IdA string	IdB string	labels int64	mechanism string	effect string	score float64	sentence string	signor_id string
P53779	P31947	1	phosphorylation	down-regulates	0.2	Here we demonstrate that activated jnk promotes bax translocation to mitochondria through phosphorylation of 14-3-3, a cytoplasmic anchor of bax. Phosphorylation of 14-3-3 led to dissociation of bax from this protein.Jnk phosphorylates 14-3-3zeta_ at ser-184 and 14-3-3sigma_ at ser-191	SIGNOR-124005
P04150	O15534	1	transcriptional regulation	up-regulates quantity by expression	0.268	GR directly regulates transcription of circadian clock components in mouse and human primary MSCs. Per2, E4bp4, Per1, and Timeless rapidly respond to glucocorticoid stimulation. Primary glucocorticoid receptor (GR) target genes are those at which GR occupies a nearby genomic glucocorticoid response element (GRE) and regulates target gene transcription	SIGNOR-268050
P46459	Q02156	0	phosphorylation	up-regulates activity	0.234	PKCepsilon phosphorylation enhances the ATPase activity of NSF.\|These results indicate that PKCepsilon phosphorylates NSF at both S460 and T461 in vitro.	SIGNOR-278300
P46527	Q13627	0	phosphorylation	up-regulates activity	0.332	DYRK1A phosphorylates p27 Kip1 at Ser10 in primary neurons and in vivo.\|Thus, our results identify DYRK1A as the predominant kinase that phosphorylates and stabilizes p27Kip1 during neuronal differentiation.	SIGNOR-278250
P15260	P49841	0	phosphorylation	up-regulates quantity by stabilization	0.2	Our data suggest that glycogen synthase kinase 3 beta (GSK3beta) phosphorylates IFNGR1 thereby enhancing receptor protein stability by limiting ubiquitin proteasomal degradation.	SIGNOR-279720
O60260	Q9BT88	1	polyubiquitination	down-regulates quantity by destabilization	0.2	Parkin binds to the C2A and C2B domains of synaptotagmin XI resulting in the polyubiquitination of synaptotagmin XI. Parkin-mediated ubiquitination also enhances the turnover of sytXI.	SIGNOR-272672
Q9GZU7	P24928	1	dephosphorylation	up-regulates activity	0.431	Phosphorylation and dephosphorylation of the C-terminal domain (CTD) of RNA polymerase II (Pol II) represent a critical regulatory checkpoint for transcription. Transcription initiation requires Fcp1/Scp1-mediated dephosphorylation of phospho-CTD. \| This combined structure-function analysis discloses the residues in Scp1 involved in CTD binding and its preferential dephosphorylation of P.Ser5 of the CTD heptad repeat.	SIGNOR-248785
P27361	Q92974	1	phosphorylation	up-regulates	0.29	Activates rhoa and as a result regulates actin assembly.	SIGNOR-160420
P55061	Q9NZS9	0	polyubiquitination	down-regulates quantity by destabilization	0.392	BAR overexpression promotes BI-1 ubiquitination and proteasomal degradation.We show here that bifunctional apoptosis regulator (BAR) functions as an ER-associated RING-type E3 ligase, interacts with BI-1, and promotes proteasomal degradation of BI-1.	SIGNOR-272778
Q9Y4K3	P51812	0	phosphorylation	up-regulates activity	0.272	These results demonstrate that TRAF6 K63 ubiquitination might be regulated by an RSK2 mediated phosphorylation dependent mechanism and phosphorylation of TRAF6 at Ser46, 47 and 48 enhances its ubiquitin mediated inflammation signaling.	SIGNOR-278302
P04179	Q16236	0	transcriptional regulation	up-regulates quantity by expression	0.45	BTG2 was found to up-regulate expression of antioxidant enzymes known to be regulated by NFE2L2, including catalase, SOD1, and SOD2	SIGNOR-254652
Q92917	P22694	0	phosphorylation	up-regulates activity	0.307	Using yeast two-hybrid screening with the PKA Cβ2 subunit as bait we identified GPKOW, also known as MOS2 homolog or T54 protein, as an interaction partner for Cβ2.PKA phosphorylates GPKOW at S27 and T316 in vitro. GPKOWs ability to bind RNA is sensitive to mutations of its PKA phosphorylation sites.	SIGNOR-266298
Q96B36	P31751	0	phosphorylation	down-regulates	0.674	Insulin-stimulated phosphorylation of pras40 by akt/pkb suppresses its mtorc1 inhibitory activity.	SIGNOR-153931
O75581	O15169	1	relocalization	down-regulates activity	0.835	The phosphorylation of lrp6 generates a docking site for axin and recruits it to the plasma membrane, where axin is inactivated and/or targeted for degradation by an unknown mechanism.	SIGNOR-148668
P01111	Q5VWQ8	0	gtpase-activating protein	down-regulates activity	0.494	The GAP domain of DAB2IP is homologous to other Ras-GAPs, such as GAP120 and neurofibromin (NF1), and can stimulate the GTPase activity of RAS proteins both in vitro and in cancer cell lines. DAB2IP is able to stimulate in vitro and in vivo the GTPase activity of RAS proteins (H-Ras, K-Ras, and N-Ras) facilitating GTP hydrolysis to GDP.	SIGNOR-254747
Q05655	Q13887	1	phosphorylation	up-regulates activity	0.335	Phosphorylation of Kruppel-like factor 5 (KLF5/IKLF) at the CBP interaction region enhances its transactivation function. \| Inhibition of protein kinase activity by H7 or calphostin C blocked both full-length and N-terminal fragment (amino acids 1-238) KLF5 activities. Mutation at a potential protein kinase C phosphorylation site within the CBP interaction domain of KLF5 reduces its transactivation function. Furthermore, using the GST pull-down approach, we showed that phosphorylation of KLF5 enhances its interaction with CBP. The results of the present study provide a mechanism for KLF5 transactivation function. \| We found that KLF5s activity was reduced to half when the serine in the potential PKC phosphorylation site was mutated to alanine (Fig. 6B, S153A) Nonetheless, the S153A mutant still retains significant transactivation activity.	SIGNOR-249206
Q13315	O75150	1	phosphorylation	up-regulates	0.443	E3 ubiquitin ligase, a heterodimeric complex of the ringfinger rfn20/rfn40 is phosphorylated by atm.	SIGNOR-175003
P30304	P01106	0	transcriptional regulation	up-regulates quantity by expression	0.627	Expression of Cdc25A is transcriptionally regulated by Myc and E2F-1 , both of which are expressed in MCF-7 cells in response to estrogen	SIGNOR-245465
P31749	P05106	1	phosphorylation	down-regulates activity	0.613	A survey of several protein kinases revealed that Thr-753 was avidly phosphorylated by PDK1 and Akt/PKB in vitro. These observations suggest that activation of PDK1 and/or Akt/PKB in platelets may modulate the binding activity and/or specificity of beta(3) for signaling molecules.	SIGNOR-252552
Q92993	P62805	1	acetylation	down-regulates activity	0.2	Thus, the TIP60 HAT complex is recruited to MYC-target genes and, probably with other other HATs, contributes to histone acetylation in response to mitogenic signals.	SIGNOR-262061
Q9Y6W5	P68400	0	phosphorylation	down-regulates	0.2	Here we identify five casein kinase 2 (ck2) phosphorylation sites within the vca domain of wave2, serines 482, 484, 488, 489, and 497. Phosphorylation of these sites is required for a high affinity interaction with the arp2/3 complex;we and show that their mutation to non-phosphorylatable alanine residues inhibits wave2 function in vivo.	SIGNOR-182350
P42224	P00519	0	phosphorylation	up-regulates activity	0.343	Our study unexpectedly found that c-Abl, another kinase other than JAKs, also contributes to STAT1 Y701 phosphorylation independently (XREF_FIG).\|reported that c-Abl, but not Arg, could induce neuronal loss by prompting STAT1 activation and interferon production.	SIGNOR-279491
O95644	P05112	1	transcriptional regulation	up-regulates quantity by expression	0.549	Recombinant NFAT1 can mediate transcription of the interleukin-2, interleukin-4, tumor necrosis factor alpha, and granulocyte-macrophage colony-stimulating factor promoters in T cells, suggesting that NFAT1 contributes to the CsA-sensitive transcription of these genes during the immune response.	SIGNOR-254498
Q14318	Q15382	0	gtpase-activating protein	down-regulates activity	0.535	Recent studies document that Rheb activates mTORC1 via direct, GTP-dependent interaction with the peptidyl-prolyl-cis/trans-isomerase FKBP38, which is proposed to act as an inhibitor of mTORC1.	SIGNOR-233568
Q06124	Q08345	0	relocalization	up-regulates activity	0.373	Overexpression of DDR1a/b increased the interaction of DDR1 with SHP-2 and up-regulated the tyrosine phosphatase activity of SHP-2.	SIGNOR-272403
P33151	P11308	0	transcriptional regulation	up-regulates quantity by expression	0.278	Erg overexpression resulted in an approximate 1.8-fold transactivation of VE-cadherin promoter activity. Thus, our data indicate that Erg drives constitutive VE-cadherin expression in human ECs	SIGNOR-261595
P04150	O00141	0	phosphorylation	up-regulates activity	0.46	SGK1 also potentiated and maintained GR activation in the presence of cortisol, and even after cortisol withdrawal, by increasing GR phosphorylation and GR nuclear translocation\|Having demonstrated that SGK1 mediates the cortisol-induced increase in GR phosphorylation at the S203 and S211 phospho-sites, which enhance GR nuclear translocation, but not at the S226 site, which inhibits nuclear translocation	SIGNOR-251669
P06241	P56945	1	phosphorylation	up-regulates activity	0.766	Taken together, these results suggest that p130Cas is directly phosphorylated by Fyn kinase in the cytoplasm of oligodendrocytes.	SIGNOR-279372
P09017	O15550	0	transcriptional regulation	up-regulates quantity by expression	0.467	Evidence for direct involvement of UTX in regulation of HOX gene activity was demonstrated through UTX knockdown experiments in HEK293T cells in which loss of UTX induced transcriptional repression of HOXA and HOXC clusters.	SIGNOR-260030
Q58F21	P62805	0	relocalization	up-regulates activity	0.2	BRDT interacts with acetylated nucleosomes via its BD1 domain. Binding may be initiated through non-specific interactions with DNA, which allow BRDT to localize to chromatin. Specificity is generated through recognition of tandem acetylated lysine residues (K5ac/K8ac) on the histone H4 tail,	SIGNOR-262066
P53350	Q96R06	1	phosphorylation	up-regulates activity	0.394	Phosphorylation of the astrin N-terminal domain by Plk1 contributes to kinetochore\u2013microtubule attachment stability.\|Taken together with the localisation data in XREF_FIG B, these data suggest that the presence of the Plk1 phosphorylated astrin N-terminus promotes the accumulation of the astrin complex at attached kinetochores, without which attachments appear more prone to dissociate.	SIGNOR-279423
Q93096	P30291	0	phosphorylation	down-regulates activity	0.2	In this study , we found that WEE1 phosphorylates PRL1 and promotes PRL1 degradation .\|In this study, we demonstrated that WEE1 phosphorylates and inhibits PRL1 to regulate alternative splicing of CYCD1;1 and CYCD3;1 , which may represent a new cell cycle control mechanism.	SIGNOR-278434
O15264	P45985	0	phosphorylation	up-regulates activity	0.459	p38-δ is activated by environmental stress, extracellular stimulants, and MAPK kinase-3, -4, -6, and -7. we investigated whether this Thr180-Gly-Tyr182 motif was essential for p38-δ activation. Taken together, these results suggest that the dual phosphorylation TGY motif is required for p38-δ activation.	SIGNOR-273956
P53779	O60282	1	phosphorylation	down-regulates activity	0.32	Mass spectrometry identified a residue in the kinesin-1 motor domain that was phosphorylated by JNK3 and this modification reduced kinesin-1 binding to microtubules. JNK3 phosphorylates kinesin-1 at Ser176	SIGNOR-262950
Q8TAS1	Q9BSJ6	1	phosphorylation	up-regulates	0.2	Cats is a substrate of kis and mapped the phosphorylation site to cats serine 131 (s131). Kis enhances the transcriptional repressor activity of cats	SIGNOR-192702
Q00526	P05412	1	phosphorylation	up-regulates	0.443	Egf-induced cdk3 activation caused c-jun phosphorylation at ser63 and ser73, resulting in increased ap-1 transactivation.	SIGNOR-183013
P51812	P06241	0	phosphorylation	up-regulates	0.326	Epidermal growth factor stimulates rsk2 activation through activation of the mek/erk pathway and src-dependent tyrosine phosphorylation of rsk2 at tyr-529. By mass spectroscopy-based studies, we identified src tyrosine kinase family members src and fyn as upstream kinases of rsk2 tyr-529.	SIGNOR-160048
O15516	Q15466	1	transcriptional regulation	up-regulates quantity by expression	0.388	CLOCK knockdown activated MTP promoter and reduced small heterodimer partner (SHP, NROB2). CLOCK upregulated SHP by binding to its E box.	SIGNOR-253698
Q14393	Q12857	0	transcriptional regulation	down-regulates quantity	0.2	By integrating transcriptomic profiling (RNA-seq) of Nfia- and Nfix-deficient GNPs with epigenomic profiling (ChIP-seq against NFIA, NFIB and NFIX, and DNase I hypersensitivity assays), we reveal that these transcription factors share a large set of potential transcriptional targets, suggestive of complementary roles for these NFI family members in promoting neural development	SIGNOR-268876
P24941	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-277831
O14920	O15530	0	phosphorylation	up-regulates activity	0.474	We found that PDK1 directly phosphorylates IKKbeta at the Ser(181) residue in the activation loop, leading to NF-kappaB nuclear translocation and NF-kappaB-dependent anti-apoptotic gene expression.	SIGNOR-279088
P46934	Q9Y4H2	1	ubiquitination	up-regulates activity	0.374	Nedd4 monoubiquitinates IRS-2, which promotes its association with Epsin1, a ubiquitin binding protein.	SIGNOR-278659
P28482	Q13541	1	phosphorylation	down-regulates activity	0.659	The 4E-BPs inhibit translation in a reversible manner. Hypophosphorylated 4E-BPs interact avidly with eIF4E, whereas 4E-BP hyperphosphorylation, elicited by stimulation of cells with hormones, cytokines, or growth factors, results in an abrogation of eIF4E-binding activity.\|These results are at variance with reports that have characterized the 4E-BP1/eIF4E interaction utilizing recombinant 4E-BP1 proteins phosphorylated in vitro with ERK, and harboring alanine substitutions at Thr 37, Thr 46, Thr 70, and Ser 83 \|phosphorylation of either Thr 46 or Ser 65 was reported to result in a decrease in eIF4E binding	SIGNOR-249390
Q15797	P50750	0	phosphorylation	down-regulates	0.32	Phosphorylation of the linker region of smad1, a receptor-activated smad (r-smad), at serine 206 (s206) and s214 induced by bmp and mediated by cdk8/9 is critical for binding of the e3 ubiquitin ligase smurf1. Binding of smurf1 leads to polyubiquitination of smad1 and its degradation by the proteasome;cdk8 and cyclint-cdk9 showed a preference for s206 and s214 but also phosphorylated s186 and s195 in the case of smad1;and t179, s208 and s213 in the case of smad3.	SIGNOR-161569
Q16539	P42224	1	phosphorylation	up-regulates activity	0.72	All stats are phosphorylated on at least one serine residue in their tad specifically, ser727 in stats 1 and 3 and ser721 in stat4. Stat serine kinases have been identified through the use of inhibitors, dominant-negative alleles, and in vitro kinase assays. They include mapk (p38mapk: stats 1, 3, 4;erk: stat3, 5;jnk: stat3), pkc_ (stat1, stat3), mtor (stat3), nlk (stat3 (42)), and camkii and ikk_ (stat1 (39, 40, 43)).STAT Serine phosphorylation regulates transcriptional activity (see below).	SIGNOR-154779
P61587	P17252	0	phosphorylation	down-regulates activity	0.2	PKCalpha dependent Rnd3 phosphorylation downregulates Rnd3 inhibitory activity and leads to increased signaling through the Rho-ROCK pathway.\|We further show that PKC\u03b1 directly phosphorylates Rnd3 in an in vitro kinase assay.	SIGNOR-279557
P50750	Q09472	1	phosphorylation	up-regulates activity	0.376	As Cdk9 phosphorylates both RNA polymerase II and p300 and increases p300-HAT activity , the effects of CUR and PyrC on the kinase activity of Cdk9 were examined .\|As Cdk9 phosphorylates both RNA polymerase II and p300 and increases p300-HAT activity, the effects of CUR and PyrC on the kinase activity of Cdk9 were examined.	SIGNOR-279690
Q9ULU4	P08254	1	transcriptional regulation	down-regulates quantity by repression	0.2	Our quantitative ChIP experiments confirmed that ZMYND8 and JARID1D were co-localized at Slug, CD44, VEGFA, and EGFR genes (Figures 4F–4I). Our ChIP results also showed that ZMYND8 repressed and occupied other JARID1D target genes, such as the matrix metalloproteinase 1 (MMP1) and MMP3, that we previously reported	SIGNOR-262043
Q13315	Q92630	1	phosphorylation	up-regulates quantity by stabilization	0.558	ATM augments nuclear stabilization of DYRK2 by inhibiting MDM2 in the apoptotic response to DNA damage\|Upon exposure to genotoxic stress, ATM phosphorylates DYRK2 at Thr-33 and Ser-369, which enables DYRK2 to escape from degradation by dissociation from MDM2 and to induce the kinase activity toward p53 at Ser-46 in the nucleus.	SIGNOR-275577
O15360	Q13315	0	phosphorylation	up-regulates	0.407	The s1449a mutant failed to completely correct a variety of fa-associated phenotypes. The dna damage response is coordinated by phosphorylation events initiated by apical kinases atm (ataxia telangectasia mutated) and atr (atm and rad3-related), and atr is essential for proper fa pathway function. Serine 1449 is in a consensus atm/atr site	SIGNOR-182949
P29474	Q14289	0	phosphorylation	down-regulates	0.309	We found that fluid shear stress induces the association of enos with the proline-rich tyrosine kinase 2 (pyk2) in endothelial cells and that the enos immunoprecipitated from enos- and pyk2-overexpressing hek293 cells was tyrosine-phosphorylated on tyr657.	SIGNOR-161824
P17302	Q13164	0	phosphorylation	down-regulates activity	0.54	Activated BMK1 selectively phosphorylates Cx43 on Ser-255 in vitro and in vivo. These data demonstrate that BMK1 kinase activity alone is both a necessary and sufficient component in the mediation of EGF-induced Cx43 Ser-255 phosphorylation and subsequent inhibition of GJC.	SIGNOR-250115
Q9NYY3	P30533	1	phosphorylation	up-regulates activity	0.3	Inhibition of Ras and activation of Rap by Plk2.\|Plk2 phosphorylation of Ras and Rap regulators controls surface AMPARs.	SIGNOR-279476
Q9UBK2	P05019	1	transcriptional regulation	up-regulates quantity by expression	0.34	PGC-1 alpha specifically induces IGF1 and represses myostatin, and expression of PGC-1a 4 in vitro and in vivo induces robust skeletal muscle hypertrophy	SIGNOR-256152
P51608	P06850	1	transcriptional regulation	down-regulates quantity by repression	0.466	Collectively, these results point to a specific association between WT MeCP2 and the methylated promoter region of Crh in vivo. In contrast, the MeCP2308 protein was not detected at the Crh promoter. \| Thus, the results of seqChIP indicate that MeCP2 preferentially associates with a transcriptionally inactive, dimethyl-histone H3 Lys-9-rich form of the Crh promoter in mice.	SIGNOR-264548
Q96LC7	Q08881	0	phosphorylation	up-regulates	0.2	These results suggest that the tyrosines at positions 597 and 667, contained within itim-like motifs, are likely targets of phosphorylation by several classes of signaling molecules, including lck, jak3, and emt. The tyrosine located at position y691 was also contributing to the phosphorylation of the wild-type siglec tail by lck and jak3 kinases. Y597 and y667 are likely involved in intracellular signaling	SIGNOR-112471
Q9HBH9	P27361	0	phosphorylation	up-regulates	0.517	Erk and p38 phosphorylate mnk1 and mnk2, which stimulates their in vitro kinase activity.	SIGNOR-48355
Q9UQB9	O75410	1	phosphorylation	up-regulates activity	0.399	Aurora-C interacts with and phosphorylates the transforming acidic coiled-coil 1 protein. The results demonstrated that TACC1 is phosphorylated by Aurora-C on a serine at position 228. although the patho-physiological meaning of TACC1 phosphorylation by Aurora-C in normal and in malignant somatic cells remains to be fully investigated, our observations suggest that Aurora-C has a role in the later stage of mitosis, when an interaction with TACC1 may be relevant for the correct progression of the cell cycle.	SIGNOR-262663
Q9ULB1	Q07666	0	post transcriptional regulation	up-regulates activity	0.332	Activity-dependent alternative splicing of Nrxn1 requires the KH-domain RNA binding protein SAM68 which associates with RNA response elements in the Nrxn1 pre-mRNA. Our findings uncover SAM68 as a key regulator of dynamic control of Nrxn1 molecular diversity and activity-dependent alternative splicing in the central nervous system.	SIGNOR-269057
P05771	P62714	0	dephosphorylation	down-regulates activity	0.469	Specifically, the threonine at position 500 (T500) on the activation loop, and T641 and S660 on the carboxyl terminus of protein kinase C beta II are phosphorylated in vivo. T500 and S660 are selectively dephosphorylated in vitro by protein phosphatase 2A to yield an enzyme that is still capable of lipid-dependent activation, whereas all three residues are dephosphorylated by protein phosphatase 1 to yield an inactive enzyme.	SIGNOR-248585
O14503	Q6R6M4	0	deubiquitination	up-regulates quantity by stabilization	0.2	Upon DNA damage, DEC1 is rapidly induced in an ATM/ATR-dependent manner. DEC1 induction results from protein stabilization via a mechanism that requires the USP17 ubiquitin protease. USP17 binds and deubiquitylates DEC1, markedly extending its half-life.	SIGNOR-276852
P09211	P00533	0	phosphorylation	up-regulates	0.437	Taken together, these results and those of the ms/ms analyses confirmed tyr-3, tyr-7, and tyr-198 to be primary residues phosphorylated by egfr in the gstp1 protein. The phosphorylation increased gstp1 enzymatic activity significantly,	SIGNOR-184387
P31751	P29474	1	phosphorylation	up-regulates activity	0.504	The phosphorylation of both S617 and S635 have also been shown to promote increased eNOS-derived NO release (Michell et al., 2002). The phosphorylaiton of S617 can be induced by PKA or Akt activity, and may serve to sensitize eNOS to calmodulin binding and modulate the phosphorylation of other eNOS sites	SIGNOR-251624
P19429	P17252	0	phosphorylation	up-regulates activity	0.343	In addition to the established phosphorylation sites (S22 and S23) we found that S38 and S165 were the other two main sites of phosphorylation. \| Phosphorylation of S22/23A also decreased its affinity for troponin C indicating that phosphorylation of S38 and/or S165 impedes binding of troponin I to troponin C. Formation of a troponin I/troponin C complex prior to cAMP-dependent protein kinase treatment did not prevent overphosphorylation.	SIGNOR-249066
Q13207	Q8N726	1	transcriptional regulation	down-regulates quantity by repression	0.522	TBX2 and TBX3 function as transcriptional repressors and both have been shown to inhibit myogenesis (Carlson et al, 2002; Zhu et al, 2014). Abnormal expression of TBX2 has been reported in several cancers including breast, pancreas, and melanoma, where it has been shown to drive proliferation (reviewed in Abrahams et al (2010)). As has been previously shown in other cell types, TBX2 was found to induce a downregulation of p14/19ARF and function as a direct repressor of p21 in RMS	SIGNOR-249594
Q12834	P24941	0	phosphorylation	down-regulates activity	0.684	Here we show that cyclin A2-Cdk2 binds and phosphorylates Cdc20 in interphase and this inhibits APC/C-Cdc20 activity.\|Interphase APC/C-Cdc20 inhibition by cyclin A2-Cdk2 ensures efficient mitotic entry.	SIGNOR-279322
Q00535	Q13153	1	phosphorylation	down-regulates activity	0.54	Our previous work revealed that the neuronal p35/Cdk5 kinase associates with Pak1 in a RacGTP-dependent manner, causing hyperphosphorylation and down-regulation of Pak1 kinase activity. We have now demonstrated direct phosphorylation of Pak1 on threonine 212 by the p35/Cdk5 kinase.	SIGNOR-249328
O75807	Q99933	0	null	down-regulates activity	0.444	Human BAG-1 proteins bind to the cellular stress response protein GADD34 and interfere with GADD34 functions.\|BAG-1 negatively modulates GADD34-bound PP1 activity, and the expression of BAG-1 isoforms can also mask GADD34-mediated inhibition of colony formation and suppression of transcription. Our findings suggest that BAG-1 may function to suppress the GADD34-mediated cellular stress response and support a role for BAG-1 in the survival of cells undergoing stress.	SIGNOR-254117
P16070	Q9ULU4	0	transcriptional regulation	down-regulates quantity by repression	0.2	Our quantitative ChIP experiments confirmed that ZMYND8 and JARID1D were co-localized at Slug, CD44, VEGFA, and EGFR genes (Figures 4F–4I). Our ChIP results also showed that ZMYND8 repressed and occupied other JARID1D target genes, such as the matrix metalloproteinase 1 (MMP1) and MMP3, that we previously reported	SIGNOR-262039
P25963	P03186	0	deubiquitination	down-regulates activity	0.2	In the current study, we have found that BPLF1 interferes with innate immune activation by targeting multiple intermediates along the TLR signal transduction pathway, including TRAF6, NEMO, and IκBα. BPLF1 can remove ubiquitin tags from proteins in the TLR signaling cascade. This inhibits TLR signaling and decreases the expression of immune response genes.	SIGNOR-266744
P19419	Q13523	0	phosphorylation	up-regulates	0.2	Activated hprp4 phosphorylates residue thr-417 on elk-1 resulting in elk-1 activation.	SIGNOR-77135
O14543	P42229	0	transcriptional regulation	up-regulates quantity by expression	0.637	We have also found SOCS2 and SOCS3 specifically induced in 32D/Flt3-ITD, both of which are STAT3/5 target genes and known negative regulators of receptor signaling	SIGNOR-261548
O00444	Q15154	1	phosphorylation	up-regulates activity	0.573	Plk4‚Äêmediated phosphorylation of PCM1 at S372 is critical for the proper localisation of centriolar satellites, its dimer formation and interaction with other satellite components\|Therefore, Plk4 is responsible for PCM1 phosphorylation at S372.	SIGNOR-279556
Q9UHD2	Q99607	1	phosphorylation	up-regulates activity	0.361	Taken together, these results suggest that in response to viral infection, ELF4 was phosphorylated by TBK1 and translocated to the nucleus in a MAVS- and STING dependent manner.\|We speculate that overexpressed ELF4 may recruit and be activated by TBK1.	SIGNOR-279130
P12931	O15455	1	phosphorylation	up-regulates activity	0.526	Markedly, Src mediated late TLR3 Pi-Tyr759 leads to the nuclear accumulation of IRF3 and IRF7 and the increase of IFN-beta production.\|Src can directly phosphorylate TLR3 Tyr759 in\nvitro and in vivo .	SIGNOR-279657
O43318	P45985	1	phosphorylation	up-regulates activity	0.711	Mitogen-activated protein kinase kinase 4 (mkk4)/stress-activated protein kinase/extracellular signal-regulated kinase (sek1), a dual-specificity kinase that phosphorylates and activates jnk, synergized with tak1 in activating jnk.Taken together, these results identify TAK1 as a regulator in the HPK1 --> TAK1 --> MKK4/SEK1 --> JNK kinase cascade and indicate the involvement of JNK in the TGF-beta signaling pathway.	SIGNOR-50618
O75460	Q15084	0	null	down-regulates activity	0.317	A resident ER protein disulfide isomerase, PDIA6, limits the duration of IRE1α activity by direct binding to cysteine148 in the luminal domain of the sensor,	SIGNOR-256536
P49840	Q9Y4H4	1	phosphorylation	down-regulates quantity by destabilization	0.2	Co-immunoprecipitation of endogenous GPSM3 and 14-3-3 proteins from the human monocytic cell line THP-1 suggests basal phosphorylation of GPSM3 at serine 35 as potentially mediated by GSK3alpha. The GPSM3/14-3-3 interaction is seen to stabilize GPSM3 from degradation and also support the nuclear exclusion of both proteins.	SIGNOR-264863
P04049	Q13153	0	phosphorylation	up-regulates	0.602	P21-activated protein kinases (paks) are serine/threonine protein kinases that phosphorylate raf-1 at ser-338 and ser-339.	SIGNOR-180808
Q9C0B5	P06241	0	phosphorylation	up-regulates quantity by stabilization	0.388	Our study demonstrates that under basal conditions, PSD-95 and Fyn cooperatively stabilize DHHC5 at the synaptic membrane through Fyn-mediated phosphorylation of DHHC5 at tyrosine residue 533 and the subsequent inhibition of DHHC5 association with endocytic proteins (Fig. 10).	SIGNOR-279738
Q9NV58	Q9Y6H5	1	ubiquitination	up-regulates quantity	0.453	Ubiquitylation of synphilin-1 by Dorfin. A, synphilin-1 is ubiquitylated in HEK293 cells. Several lines of evidence have suggested that derangements in the ubiquitin-proteasome protein degradation pathway may have a prominent role in the pathogenesis of PD (5). Our present study shows that Dorfin, an E3 ubiquityl ligase, is colocalized with ubiquitin in LBs of PD and physically binds to ubiquitylate synphilin-1, which is known to be a major component of LBs	SIGNOR-271455
P60484	O14641	1	dephosphorylation	down-regulates activity	0.318	This showed that while both PTEN WT and the lipid phosphatase-inactive G129E mutant suppressed phosphorylation of DVL2 on serine 143 that accumulated upon PTEN knockdown, the C124S and Y138L mutants did not .\|Finally, it is important to point out that while our studies show that PTEN can directly dephosphorylate DVL2 in vitro, it is possible that regulation of serine 143 phosphorylation of DVL2 by PTEN in cells may require additional protein factors, or post-translational modifications.	SIGNOR-277035
Q96F46	P49840	0	phosphorylation	down-regulates quantity by destabilization	0.2	Glycogen synthase kinase 3 (GSK3) constitutively bound to and phosphorylated IL-17RA at T780, leading to ubiquitination and proteasome-mediated degradation of IL-17RA, thus inhibiting IL-17-mediated inflammation.	SIGNOR-277206
O15530	P04049	1	phosphorylation	up-regulates activity	0.311	PDK1, but not PKCs, phosphorylate and activate Raf1 in MAPK pathway when platelets are stimulated with 2MeSADP.	SIGNOR-280063
P05771	Q9H1D0	1	phosphorylation	down-regulates activity	0.2	This regulation requires PKC(betaII) and defined phosphorylation sites within the ARD and the C-terminus. Both regulatory sites act synergistically to constitute a novel mechanism by which ATP stabilizes channel activity and acts as a metabolic switch for Ca(2+) influx. Decreases in ATP concentration or activation of PKC(betaII) disable regulation of the channels by ATP, rendering them more susceptible to inactivation and rundown and preventing Ca(2+) overload.	SIGNOR-276265
P84243	Q14493	0	translation regulation	up-regulates quantity by expression	0.2	Synthesis of mature histone mRNA requires only a single processing reaction: an endonucleolytic cleavage between a conserved stem-loop and a purine-rich downstream element to form the 3' end. The stem-loop binding protein (SLBP) is required for processing, and following processing, histone mRNA is transported to the cytoplasm, where SLBP participates in translation of the histone mRNA\|We used radiolabeled probes generated by PCR targeting the open reading frame (ORF) to detect histones H2A, H2B, H3, H4, and H1 and used 7SK snRNA as a loading control (Fig. 2A). The abundance of histone H2A, H2B, H3, and H4 mRNAs is reduced to 37% to 70% of control levels in the SLBP knockdown cells when compared to the C2 control.	SIGNOR-265418
P06241	P17706	0	dephosphorylation	down-regulates	0.325	Previously, we reported that sfks can serve as bona fide substrates for tcptp and that tcptp dephosphorylates the y418 activation loop autophosphorylation site (corresponding to y394 in lck and y417 in fyn) to inactivate sfks	SIGNOR-177113
O15350	O00308	0	polyubiquitination	down-regulates quantity by destabilization	0.283	WWP2 ubiquitinates p73 and controls its protein stability. In our study, we identified WWP2, an E3 ligase, as a novel p73-associated protein that ubiquitinates and degrades p73. In contrast, WWP2 heterodimerizes with another E3 ligase, WWP1, which specifically ubiquitinates and degrades ΔNp73.	SIGNOR-272233
P05412	P98066	1	transcriptional regulation	up-regulates quantity by expression	0.308	Tumor necrosis factor (TNF)-stimulated gene 6 (TSG-6) encodes a protein expressed during inflammation. We have previously shown that transcription factors of the NF-IL6 and AP-1 families cooperatively modulate activation of the TSG-6 gene by TNF or interleukin 1 (IL-1) through a promoter region that contains an NF-IL6 site (-106 to -114) and an AP-1 element	SIGNOR-254052
P17612	Q04206	1	phosphorylation	up-regulates	0.516	The transcriptional activity of nf-kappa b is stimulated upon phosphorylation of its p65 subunit on serine 276 by protein kinase a (pka).	SIGNOR-58972
Q8WXG6	P20336	1	guanine nucleotide exchange factor	up-regulates activity	0.396	Rab3A, a member of the Rab3 small G protein family, regulates Ca(2+)-dependent exocytosis of neurotransmitter. The cyclical activation and inactivation of Rab3A are essential for the Rab3A action in exocytosis. GDP-Rab3A is activated to GTP-Rab3A by Rab3 GDP/GTP exchange protein (Rab3 GEP), and GTP-Rab3A is inactivated to GDP-Rab3A by Rab3 GTPase-activating protein (Rab3 GAP).	SIGNOR-265579
Q02763	P42224	1	phosphorylation	up-regulates activity	0.301	Tie2-R849W induced STAT1 phosphorylation at Y701 independent of ligand stimulation.\|Together, Tie2-R849W induced functional activation of STAT1, leading to increased expression of STAT1-responsive gene like IRF1.	SIGNOR-279131
Q13586	Q8IXL6	0	phosphorylation	up-regulates activity	0.2	Similarly, STIM1 is phosphorylated on S88 by FAM20C both in vitro and in vivo.	SIGNOR-279173
Q13233	Q13546	0	phosphorylation	up-regulates activity	0.455	These findings strongly suggest that rip phosphorylates mekk1 at ser-957 and ser-994.	SIGNOR-108257
P12931	Q8IXJ6	1	phosphorylation	down-regulates quantity by destabilization	0.291	In this study, we investigated the potential regulation of SIRT2 function by c-Src. We found that the protein levels of SIRT2 were decreased by c-Src, and subsequently rescued by the addition of a Src specific inhibitor, SU6656, or by siRNA-mediated knockdown of c-Src. The c-Src interacts with and phosphorylates SIRT2 at Tyr104.	SIGNOR-263104
O43150	Q14289	0	phosphorylation	up-regulates activity	0.525	Tyrosine phosphorylation of Pap by Pyk2 or Src kinases. We have identified a new Pyk2 binding protein designated Pap. Pap is a multidomain protein composed of an N-terminal alpha-helical region with a coiled-coil motif, followed by a pleckstrin homology domain, an Arf-GAP domain, an ankyrin homology region, a proline-rich region, and a C-terminal SH3 domain. We demonstrate that Pap forms a stable complex with Pyk2 and that activation of Pyk2 leads to tyrosine phosphorylation of Pap in living cells.	SIGNOR-269704
Q9H3D4	Q96SW2	0	polyubiquitination	down-regulates quantity by destabilization	0.2	CRBN functions as a substrate receptor of the E3 ubiquitin ligase CRL4, whose substrate specificity is modulated by thalidomide and its analogs.When thalidomide binds to CRBN, substrate specificity of CRL4CRBN is altered and CRBN neomorphically binds to ∆Np63, TAp63 and other neosubstrates and ubiquitinates them for proteasomal degradation.	SIGNOR-272214
O14757	P06493	0	phosphorylation	up-regulates	0.411	Chk1 itself is also subject to cdk-mediated phosphorylation at serines 286 and 301 (s286 and 301). We show that chk1 s301 phosphorylation increases as cells progress through s and g2 and that both cdk1 and cdk2 are likely to contribute to this modification in vivo. We also find that substitution of s286 and s301 with non-phosphorylatable alanine residues strongly attenuates dna damage-induced chk1 activation and g2 checkpoint proficiency	SIGNOR-175071
Q2M2Z5	P53350	0	phosphorylation	up-regulates	0.519	Here, we identify a novel centrosomal substrate of plk1, kizuna (kiz), depletion of which causes fragmentation and dissociation of the pericentriolar material from centrioles at prometaphase, resulting in multipolar spindles. Plk1 maintains the integrity of the spindle poles by phosphorylating kiz.	SIGNOR-149630
P11678	P13727	1	post translational modification	up-regulates activity	0.434	Human eosinophils are bone marrow-derived, non-dividing granulocytes of the innate immune system, which store the highly cationic proteins eosinophil peroxidase (EPO), major basic protein (MBP), eosinophil-derived neurotoxin (EDN), and eosinophil cationic protein (ECP) in secondary granules. we demonstrated that Tyr nitration of the eosinophil granule proteins is exclusively mediated by EPO, in the presence of functional NADPH oxidase and minute amounts of NOx. EPO appears to nitrate itself via an autocatalytic mechanism.	SIGNOR-261703

P53779

P31947

1

phosphorylation

down-regulates

0.2

Here we demonstrate that activated jnk promotes bax translocation to mitochondria through phosphorylation of 14-3-3, a cytoplasmic anchor of bax. Phosphorylation of 14-3-3 led to dissociation of bax from this protein.Jnk phosphorylates 14-3-3zeta_ at ser-184 and 14-3-3sigma_ at ser-191

SIGNOR-124005

P04150

O15534

1

transcriptional regulation

up-regulates quantity by expression

0.268

GR directly regulates transcription of circadian clock components in mouse and human primary MSCs. Per2, E4bp4, Per1, and Timeless rapidly respond to glucocorticoid stimulation. Primary glucocorticoid receptor (GR) target genes are those at which GR occupies a nearby genomic glucocorticoid response element (GRE) and regulates target gene transcription

SIGNOR-268050

P46459

Q02156

0

phosphorylation

up-regulates activity

0.234

PKCepsilon phosphorylation enhances the ATPase activity of NSF.|These results indicate that PKCepsilon phosphorylates NSF at both S460 and T461 in vitro.

SIGNOR-278300

P46527

Q13627

0

phosphorylation

up-regulates activity

0.332

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

SIGNOR-278250

P15260

P49841

0

phosphorylation

up-regulates quantity by stabilization

0.2

Our data suggest that glycogen synthase kinase 3 beta (GSK3beta) phosphorylates IFNGR1 thereby enhancing receptor protein stability by limiting ubiquitin proteasomal degradation.

SIGNOR-279720

O60260

Q9BT88

1

polyubiquitination

down-regulates quantity by destabilization

0.2

Parkin binds to the C2A and C2B domains of synaptotagmin XI resulting in the polyubiquitination of synaptotagmin XI. Parkin-mediated ubiquitination also enhances the turnover of sytXI.

SIGNOR-272672

Q9GZU7

P24928

1

dephosphorylation

up-regulates activity

0.431

Phosphorylation and dephosphorylation of the C-terminal domain (CTD) of RNA polymerase II (Pol II) represent a critical regulatory checkpoint for transcription. Transcription initiation requires Fcp1/Scp1-mediated dephosphorylation of phospho-CTD. | This combined structure-function analysis discloses the residues in Scp1 involved in CTD binding and its preferential dephosphorylation of P.Ser5 of the CTD heptad repeat.

SIGNOR-248785

P27361

Q92974

1

phosphorylation

up-regulates

0.29

Activates rhoa and as a result regulates actin assembly.

SIGNOR-160420

P55061

Q9NZS9

0

polyubiquitination

down-regulates quantity by destabilization

0.392

BAR overexpression promotes BI-1 ubiquitination and proteasomal degradation.We show here that bifunctional apoptosis regulator (BAR) functions as an ER-associated RING-type E3 ligase, interacts with BI-1, and promotes proteasomal degradation of BI-1.

SIGNOR-272778

Q9Y4K3

P51812

0

phosphorylation

up-regulates activity

0.272

These results demonstrate that TRAF6 K63 ubiquitination might be regulated by an RSK2 mediated phosphorylation dependent mechanism and phosphorylation of TRAF6 at Ser46, 47 and 48 enhances its ubiquitin mediated inflammation signaling.

SIGNOR-278302

P04179

Q16236

0

transcriptional regulation

up-regulates quantity by expression

0.45

BTG2 was found to up-regulate expression of antioxidant enzymes known to be regulated by NFE2L2, including catalase, SOD1, and SOD2

SIGNOR-254652

Q92917

P22694

0

phosphorylation

up-regulates activity

0.307

Using yeast two-hybrid screening with the PKA Cβ2 subunit as bait we identified GPKOW, also known as MOS2 homolog or T54 protein, as an interaction partner for Cβ2.PKA phosphorylates GPKOW at S27 and T316 in vitro. GPKOWs ability to bind RNA is sensitive to mutations of its PKA phosphorylation sites.

SIGNOR-266298

Q96B36

P31751

0

phosphorylation

down-regulates

0.674

Insulin-stimulated phosphorylation of pras40 by akt/pkb suppresses its mtorc1 inhibitory activity.

SIGNOR-153931

O75581

O15169

1

relocalization

down-regulates activity

0.835

The phosphorylation of lrp6 generates a docking site for axin and recruits it to the plasma membrane, where axin is inactivated and/or targeted for degradation by an unknown mechanism.

SIGNOR-148668

P01111

Q5VWQ8

0

gtpase-activating protein

down-regulates activity

0.494

The GAP domain of DAB2IP is homologous to other Ras-GAPs, such as GAP120 and neurofibromin (NF1), and can stimulate the GTPase activity of RAS proteins both in vitro and in cancer cell lines. DAB2IP is able to stimulate in vitro and in vivo the GTPase activity of RAS proteins (H-Ras, K-Ras, and N-Ras) facilitating GTP hydrolysis to GDP.

SIGNOR-254747

Q05655

Q13887

1

phosphorylation

up-regulates activity

0.335

Phosphorylation of Kruppel-like factor 5 (KLF5/IKLF) at the CBP interaction region enhances its transactivation function. | Inhibition of protein kinase activity by H7 or calphostin C blocked both full-length and N-terminal fragment (amino acids 1-238) KLF5 activities. Mutation at a potential protein kinase C phosphorylation site within the CBP interaction domain of KLF5 reduces its transactivation function. Furthermore, using the GST pull-down approach, we showed that phosphorylation of KLF5 enhances its interaction with CBP. The results of the present study provide a mechanism for KLF5 transactivation function. | We found that KLF5s activity was reduced to half when the serine in the potential PKC phosphorylation site was mutated to alanine (Fig. 6B, S153A) Nonetheless, the S153A mutant still retains significant transactivation activity.

SIGNOR-249206

Q13315

O75150

1

phosphorylation

up-regulates

0.443

E3 ubiquitin ligase, a heterodimeric complex of the ringfinger rfn20/rfn40 is phosphorylated by atm.

SIGNOR-175003

P30304

P01106

0

transcriptional regulation

up-regulates quantity by expression

0.627

Expression of Cdc25A is transcriptionally regulated by Myc and E2F-1 , both of which are expressed in MCF-7 cells in response to estrogen

SIGNOR-245465

P31749

P05106

1

phosphorylation

down-regulates activity

0.613

A survey of several protein kinases revealed that Thr-753 was avidly phosphorylated by PDK1 and Akt/PKB in vitro. These observations suggest that activation of PDK1 and/or Akt/PKB in platelets may modulate the binding activity and/or specificity of beta(3) for signaling molecules.

SIGNOR-252552

Q92993

P62805

1

acetylation

down-regulates activity

0.2

Thus, the TIP60 HAT complex is recruited to MYC-target genes and, probably with other other HATs, contributes to histone acetylation in response to mitogenic signals.

SIGNOR-262061

Q9Y6W5

P68400

0

phosphorylation

down-regulates

0.2

Here we identify five casein kinase 2 (ck2) phosphorylation sites within the vca domain of wave2, serines 482, 484, 488, 489, and 497. Phosphorylation of these sites is required for a high affinity interaction with the arp2/3 complex;we and show that their mutation to non-phosphorylatable alanine residues inhibits wave2 function in vivo.

SIGNOR-182350

P42224

P00519

0

phosphorylation

up-regulates activity

0.343

Our study unexpectedly found that c-Abl, another kinase other than JAKs, also contributes to STAT1 Y701 phosphorylation independently (XREF_FIG).|reported that c-Abl, but not Arg, could induce neuronal loss by prompting STAT1 activation and interferon production.

SIGNOR-279491

O95644

P05112

1

transcriptional regulation

up-regulates quantity by expression

0.549

Recombinant NFAT1 can mediate transcription of the interleukin-2, interleukin-4, tumor necrosis factor alpha, and granulocyte-macrophage colony-stimulating factor promoters in T cells, suggesting that NFAT1 contributes to the CsA-sensitive transcription of these genes during the immune response.

SIGNOR-254498

Q14318

Q15382

0

gtpase-activating protein

down-regulates activity

0.535

Recent studies document that Rheb activates mTORC1 via direct, GTP-dependent interaction with the peptidyl-prolyl-cis/trans-isomerase FKBP38, which is proposed to act as an inhibitor of mTORC1.

SIGNOR-233568

Q06124

Q08345

0

relocalization

up-regulates activity

0.373

Overexpression of DDR1a/b increased the interaction of DDR1 with SHP-2 and up-regulated the tyrosine phosphatase activity of SHP-2.

SIGNOR-272403

P33151

P11308

0

transcriptional regulation

up-regulates quantity by expression

0.278

Erg overexpression resulted in an approximate 1.8-fold transactivation of VE-cadherin promoter activity. Thus, our data indicate that Erg drives constitutive VE-cadherin expression in human ECs

SIGNOR-261595

P04150

O00141

0

phosphorylation

up-regulates activity

0.46

SGK1 also potentiated and maintained GR activation in the presence of cortisol, and even after cortisol withdrawal, by increasing GR phosphorylation and GR nuclear translocation|Having demonstrated that SGK1 mediates the cortisol-induced increase in GR phosphorylation at the S203 and S211 phospho-sites, which enhance GR nuclear translocation, but not at the S226 site, which inhibits nuclear translocation

SIGNOR-251669

P06241

P56945

1

phosphorylation

up-regulates activity

0.766

Taken together, these results suggest that p130Cas is directly phosphorylated by Fyn kinase in the cytoplasm of oligodendrocytes.

SIGNOR-279372

P09017

O15550

0

transcriptional regulation

up-regulates quantity by expression

0.467

Evidence for direct involvement of UTX in regulation of HOX gene activity was demonstrated through UTX knockdown experiments in HEK293T cells in which loss of UTX induced transcriptional repression of HOXA and HOXC clusters.

SIGNOR-260030

Q58F21

P62805

0

relocalization

up-regulates activity

0.2

BRDT interacts with acetylated nucleosomes via its BD1 domain. Binding may be initiated through non-specific interactions with DNA, which allow BRDT to localize to chromatin. Specificity is generated through recognition of tandem acetylated lysine residues (K5ac/K8ac) on the histone H4 tail,

SIGNOR-262066

P53350

Q96R06

1

phosphorylation

up-regulates activity

0.394

Phosphorylation of the astrin N-terminal domain by Plk1 contributes to kinetochore\u2013microtubule attachment stability.|Taken together with the localisation data in XREF_FIG B, these data suggest that the presence of the Plk1 phosphorylated astrin N-terminus promotes the accumulation of the astrin complex at attached kinetochores, without which attachments appear more prone to dissociate.

SIGNOR-279423

Q93096

P30291

0

phosphorylation

down-regulates activity

0.2

In this study , we found that WEE1 phosphorylates PRL1 and promotes PRL1 degradation .|In this study, we demonstrated that WEE1 phosphorylates and inhibits PRL1 to regulate alternative splicing of CYCD1;1 and CYCD3;1 , which may represent a new cell cycle control mechanism.

SIGNOR-278434

O15264

P45985

0

phosphorylation

up-regulates activity

0.459

p38-δ is activated by environmental stress, extracellular stimulants, and MAPK kinase-3, -4, -6, and -7. we investigated whether this Thr180-Gly-Tyr182 motif was essential for p38-δ activation. Taken together, these results suggest that the dual phosphorylation TGY motif is required for p38-δ activation.

SIGNOR-273956

P53779

O60282

1

phosphorylation

down-regulates activity

0.32

Mass spectrometry identified a residue in the kinesin-1 motor domain that was phosphorylated by JNK3 and this modification reduced kinesin-1 binding to microtubules. JNK3 phosphorylates kinesin-1 at Ser176

SIGNOR-262950

Q8TAS1

Q9BSJ6

1

phosphorylation

up-regulates

0.2

Cats is a substrate of kis and mapped the phosphorylation site to cats serine 131 (s131). Kis enhances the transcriptional repressor activity of cats

SIGNOR-192702

Q00526

P05412

1

phosphorylation

up-regulates

0.443

Egf-induced cdk3 activation caused c-jun phosphorylation at ser63 and ser73, resulting in increased ap-1 transactivation.

SIGNOR-183013

P51812

P06241

0

phosphorylation

up-regulates

0.326

Epidermal growth factor stimulates rsk2 activation through activation of the mek/erk pathway and src-dependent tyrosine phosphorylation of rsk2 at tyr-529. By mass spectroscopy-based studies, we identified src tyrosine kinase family members src and fyn as upstream kinases of rsk2 tyr-529.

SIGNOR-160048

O15516

Q15466

1

transcriptional regulation

up-regulates quantity by expression

0.388

CLOCK knockdown activated MTP promoter and reduced small heterodimer partner (SHP, NROB2). CLOCK upregulated SHP by binding to its E box.

SIGNOR-253698

Q14393

Q12857

0

transcriptional regulation

down-regulates quantity

0.2

By integrating transcriptomic profiling (RNA-seq) of Nfia- and Nfix-deficient GNPs with epigenomic profiling (ChIP-seq against NFIA, NFIB and NFIX, and DNase I hypersensitivity assays), we reveal that these transcription factors share a large set of potential transcriptional targets, suggestive of complementary roles for these NFI family members in promoting neural development

SIGNOR-268876

P24941

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-277831

O14920

O15530

0

phosphorylation

up-regulates activity

0.474

We found that PDK1 directly phosphorylates IKKbeta at the Ser(181) residue in the activation loop, leading to NF-kappaB nuclear translocation and NF-kappaB-dependent anti-apoptotic gene expression.

SIGNOR-279088

P46934

Q9Y4H2

1

ubiquitination

up-regulates activity

0.374

Nedd4 monoubiquitinates IRS-2, which promotes its association with Epsin1, a ubiquitin binding protein.

SIGNOR-278659

P28482

Q13541

1

phosphorylation

down-regulates activity

0.659

The 4E-BPs inhibit translation in a reversible manner. Hypophosphorylated 4E-BPs interact avidly with eIF4E, whereas 4E-BP hyperphosphorylation, elicited by stimulation of cells with hormones, cytokines, or growth factors, results in an abrogation of eIF4E-binding activity.|These results are at variance with reports that have characterized the 4E-BP1/eIF4E interaction utilizing recombinant 4E-BP1 proteins phosphorylated in vitro with ERK, and harboring alanine substitutions at Thr 37, Thr 46, Thr 70, and Ser 83 |phosphorylation of either Thr 46 or Ser 65 was reported to result in a decrease in eIF4E binding

SIGNOR-249390

Q15797

P50750

0

phosphorylation

down-regulates

0.32

Phosphorylation of the linker region of smad1, a receptor-activated smad (r-smad), at serine 206 (s206) and s214 induced by bmp and mediated by cdk8/9 is critical for binding of the e3 ubiquitin ligase smurf1. Binding of smurf1 leads to polyubiquitination of smad1 and its degradation by the proteasome;cdk8 and cyclint-cdk9 showed a preference for s206 and s214 but also phosphorylated s186 and s195 in the case of smad1;and t179, s208 and s213 in the case of smad3.

SIGNOR-161569

Q16539

P42224

1

phosphorylation

up-regulates activity

0.72

All stats are phosphorylated on at least one serine residue in their tad specifically, ser727 in stats 1 and 3 and ser721 in stat4. Stat serine kinases have been identified through the use of inhibitors, dominant-negative alleles, and in vitro kinase assays. They include mapk (p38mapk: stats 1, 3, 4;erk: stat3, 5;jnk: stat3), pkc_ (stat1, stat3), mtor (stat3), nlk (stat3 (42)), and camkii and ikk_ (stat1 (39, 40, 43)).STAT Serine phosphorylation regulates transcriptional activity (see below).

SIGNOR-154779

P61587

P17252

0

phosphorylation

down-regulates activity

0.2

PKCalpha dependent Rnd3 phosphorylation downregulates Rnd3 inhibitory activity and leads to increased signaling through the Rho-ROCK pathway.|We further show that PKC\u03b1 directly phosphorylates Rnd3 in an in vitro kinase assay.

SIGNOR-279557

P50750

Q09472

1

phosphorylation

up-regulates activity

0.376

As Cdk9 phosphorylates both RNA polymerase II and p300 and increases p300-HAT activity , the effects of CUR and PyrC on the kinase activity of Cdk9 were examined .|As Cdk9 phosphorylates both RNA polymerase II and p300 and increases p300-HAT activity, the effects of CUR and PyrC on the kinase activity of Cdk9 were examined.

SIGNOR-279690

Q9ULU4

P08254

1

transcriptional regulation

down-regulates quantity by repression

0.2

Our quantitative ChIP experiments confirmed that ZMYND8 and JARID1D were co-localized at Slug, CD44, VEGFA, and EGFR genes (Figures 4F–4I). Our ChIP results also showed that ZMYND8 repressed and occupied other JARID1D target genes, such as the matrix metalloproteinase 1 (MMP1) and MMP3, that we previously reported

SIGNOR-262043

Q13315

Q92630

1

phosphorylation

up-regulates quantity by stabilization

0.558

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

SIGNOR-275577

O15360

Q13315

0

phosphorylation

up-regulates

0.407

The s1449a mutant failed to completely correct a variety of fa-associated phenotypes. The dna damage response is coordinated by phosphorylation events initiated by apical kinases atm (ataxia telangectasia mutated) and atr (atm and rad3-related), and atr is essential for proper fa pathway function. Serine 1449 is in a consensus atm/atr site

SIGNOR-182949

P29474

Q14289

0

phosphorylation

down-regulates

0.309

We found that fluid shear stress induces the association of enos with the proline-rich tyrosine kinase 2 (pyk2) in endothelial cells and that the enos immunoprecipitated from enos- and pyk2-overexpressing hek293 cells was tyrosine-phosphorylated on tyr657.

SIGNOR-161824

P17302

Q13164

0

phosphorylation

down-regulates activity

0.54

Activated BMK1 selectively phosphorylates Cx43 on Ser-255 in vitro and in vivo. These data demonstrate that BMK1 kinase activity alone is both a necessary and sufficient component in the mediation of EGF-induced Cx43 Ser-255 phosphorylation and subsequent inhibition of GJC.

SIGNOR-250115

Q9NYY3

P30533

1

phosphorylation

up-regulates activity

0.3

Inhibition of Ras and activation of Rap by Plk2.|Plk2 phosphorylation of Ras and Rap regulators controls surface AMPARs.

SIGNOR-279476

Q9UBK2

P05019

1

transcriptional regulation

up-regulates quantity by expression

0.34

PGC-1 alpha specifically induces IGF1 and represses myostatin, and expression of PGC-1a 4 in vitro and in vivo induces robust skeletal muscle hypertrophy

SIGNOR-256152

P51608

P06850

1

transcriptional regulation

down-regulates quantity by repression

0.466

Collectively, these results point to a specific association between WT MeCP2 and the methylated promoter region of Crh in vivo. In contrast, the MeCP2308 protein was not detected at the Crh promoter. | Thus, the results of seqChIP indicate that MeCP2 preferentially associates with a transcriptionally inactive, dimethyl-histone H3 Lys-9-rich form of the Crh promoter in mice.

SIGNOR-264548

Q96LC7

Q08881

0

phosphorylation

up-regulates

0.2

These results suggest that the tyrosines at positions 597 and 667, contained within itim-like motifs, are likely targets of phosphorylation by several classes of signaling molecules, including lck, jak3, and emt. The tyrosine located at position y691 was also contributing to the phosphorylation of the wild-type siglec tail by lck and jak3 kinases. Y597 and y667 are likely involved in intracellular signaling

SIGNOR-112471

Q9HBH9

P27361

0

phosphorylation

up-regulates

0.517

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

SIGNOR-48355

Q9UQB9

O75410

1

phosphorylation

up-regulates activity

0.399

Aurora-C interacts with and phosphorylates the transforming acidic coiled-coil 1 protein. The results demonstrated that TACC1 is phosphorylated by Aurora-C on a serine at position 228. although the patho-physiological meaning of TACC1 phosphorylation by Aurora-C in normal and in malignant somatic cells remains to be fully investigated, our observations suggest that Aurora-C has a role in the later stage of mitosis, when an interaction with TACC1 may be relevant for the correct progression of the cell cycle.

SIGNOR-262663

Q9ULB1

Q07666

0

post transcriptional regulation

up-regulates activity

0.332

Activity-dependent alternative splicing of Nrxn1 requires the KH-domain RNA binding protein SAM68 which associates with RNA response elements in the Nrxn1 pre-mRNA. Our findings uncover SAM68 as a key regulator of dynamic control of Nrxn1 molecular diversity and activity-dependent alternative splicing in the central nervous system.

SIGNOR-269057

P05771

P62714

0

dephosphorylation

down-regulates activity

0.469

Specifically, the threonine at position 500 (T500) on the activation loop, and T641 and S660 on the carboxyl terminus of protein kinase C beta II are phosphorylated in vivo. T500 and S660 are selectively dephosphorylated in vitro by protein phosphatase 2A to yield an enzyme that is still capable of lipid-dependent activation, whereas all three residues are dephosphorylated by protein phosphatase 1 to yield an inactive enzyme.

SIGNOR-248585

O14503

Q6R6M4

0

deubiquitination

up-regulates quantity by stabilization

0.2

Upon DNA damage, DEC1 is rapidly induced in an ATM/ATR-dependent manner. DEC1 induction results from protein stabilization via a mechanism that requires the USP17 ubiquitin protease. USP17 binds and deubiquitylates DEC1, markedly extending its half-life.

SIGNOR-276852

P09211

P00533

0

phosphorylation

up-regulates

0.437

Taken together, these results and those of the ms/ms analyses confirmed tyr-3, tyr-7, and tyr-198 to be primary residues phosphorylated by egfr in the gstp1 protein. The phosphorylation increased gstp1 enzymatic activity significantly,

SIGNOR-184387

P31751

P29474

1

phosphorylation

up-regulates activity

0.504

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

SIGNOR-251624

P19429

P17252

0

phosphorylation

up-regulates activity

0.343

In addition to the established phosphorylation sites (S22 and S23) we found that S38 and S165 were the other two main sites of phosphorylation. | Phosphorylation of S22/23A also decreased its affinity for troponin C indicating that phosphorylation of S38 and/or S165 impedes binding of troponin I to troponin C. Formation of a troponin I/troponin C complex prior to cAMP-dependent protein kinase treatment did not prevent overphosphorylation.

SIGNOR-249066

Q13207

Q8N726

1

transcriptional regulation

down-regulates quantity by repression

0.522

TBX2 and TBX3 function as transcriptional repressors and both have been shown to inhibit myogenesis (Carlson et al, 2002; Zhu et al, 2014). Abnormal expression of TBX2 has been reported in several cancers including breast, pancreas, and melanoma, where it has been shown to drive proliferation (reviewed in Abrahams et al (2010)). As has been previously shown in other cell types, TBX2 was found to induce a downregulation of p14/19ARF and function as a direct repressor of p21 in RMS

SIGNOR-249594

Q12834

P24941

0

phosphorylation

down-regulates activity

0.684

Here we show that cyclin A2-Cdk2 binds and phosphorylates Cdc20 in interphase and this inhibits APC/C-Cdc20 activity.|Interphase APC/C-Cdc20 inhibition by cyclin A2-Cdk2 ensures efficient mitotic entry.

SIGNOR-279322

Q00535

Q13153

1

phosphorylation

down-regulates activity

0.54

Our previous work revealed that the neuronal p35/Cdk5 kinase associates with Pak1 in a RacGTP-dependent manner, causing hyperphosphorylation and down-regulation of Pak1 kinase activity. We have now demonstrated direct phosphorylation of Pak1 on threonine 212 by the p35/Cdk5 kinase.

SIGNOR-249328

O75807

Q99933

0

null

down-regulates activity

0.444

Human BAG-1 proteins bind to the cellular stress response protein GADD34 and interfere with GADD34 functions.|BAG-1 negatively modulates GADD34-bound PP1 activity, and the expression of BAG-1 isoforms can also mask GADD34-mediated inhibition of colony formation and suppression of transcription. Our findings suggest that BAG-1 may function to suppress the GADD34-mediated cellular stress response and support a role for BAG-1 in the survival of cells undergoing stress.

SIGNOR-254117

P16070

Q9ULU4

0

transcriptional regulation

down-regulates quantity by repression

0.2

Our quantitative ChIP experiments confirmed that ZMYND8 and JARID1D were co-localized at Slug, CD44, VEGFA, and EGFR genes (Figures 4F–4I). Our ChIP results also showed that ZMYND8 repressed and occupied other JARID1D target genes, such as the matrix metalloproteinase 1 (MMP1) and MMP3, that we previously reported

SIGNOR-262039

P25963

P03186

0

deubiquitination

down-regulates activity

0.2

In the current study, we have found that BPLF1 interferes with innate immune activation by targeting multiple intermediates along the TLR signal transduction pathway, including TRAF6, NEMO, and IκBα. BPLF1 can remove ubiquitin tags from proteins in the TLR signaling cascade. This inhibits TLR signaling and decreases the expression of immune response genes.

SIGNOR-266744

P19419

Q13523

0

phosphorylation

up-regulates

0.2

Activated hprp4 phosphorylates residue thr-417 on elk-1 resulting in elk-1 activation.

SIGNOR-77135

O14543

P42229

0

transcriptional regulation

up-regulates quantity by expression

0.637

We have also found SOCS2 and SOCS3 specifically induced in 32D/Flt3-ITD, both of which are STAT3/5 target genes and known negative regulators of receptor signaling

SIGNOR-261548

O00444

Q15154

1

phosphorylation

up-regulates activity

0.573

Plk4‚Äêmediated phosphorylation of PCM1 at S372 is critical for the proper localisation of centriolar satellites, its dimer formation and interaction with other satellite components|Therefore, Plk4 is responsible for PCM1 phosphorylation at S372.

SIGNOR-279556

Q9UHD2

Q99607

1

phosphorylation

up-regulates activity

0.361

Taken together, these results suggest that in response to viral infection, ELF4 was phosphorylated by TBK1 and translocated to the nucleus in a MAVS- and STING dependent manner.|We speculate that overexpressed ELF4 may recruit and be activated by TBK1.

SIGNOR-279130

P12931

O15455

1

phosphorylation

up-regulates activity

0.526

Markedly, Src mediated late TLR3 Pi-Tyr759 leads to the nuclear accumulation of IRF3 and IRF7 and the increase of IFN-beta production.|Src can directly phosphorylate TLR3 Tyr759 in\nvitro and in vivo .

SIGNOR-279657

O43318

P45985

1

phosphorylation

up-regulates activity

0.711

Mitogen-activated protein kinase kinase 4 (mkk4)/stress-activated protein kinase/extracellular signal-regulated kinase (sek1), a dual-specificity kinase that phosphorylates and activates jnk, synergized with tak1 in activating jnk.Taken together, these results identify TAK1 as a regulator in the HPK1 --> TAK1 --> MKK4/SEK1 --> JNK kinase cascade and indicate the involvement of JNK in the TGF-beta signaling pathway.

SIGNOR-50618

O75460

Q15084

0

null

down-regulates activity

0.317

A resident ER protein disulfide isomerase, PDIA6, limits the duration of IRE1α activity by direct binding to cysteine148 in the luminal domain of the sensor,

SIGNOR-256536

P49840

Q9Y4H4

1

phosphorylation

down-regulates quantity by destabilization

0.2

Co-immunoprecipitation of endogenous GPSM3 and 14-3-3 proteins from the human monocytic cell line THP-1 suggests basal phosphorylation of GPSM3 at serine 35 as potentially mediated by GSK3alpha. The GPSM3/14-3-3 interaction is seen to stabilize GPSM3 from degradation and also support the nuclear exclusion of both proteins.

SIGNOR-264863

P04049

Q13153

0

phosphorylation

up-regulates

0.602

P21-activated protein kinases (paks) are serine/threonine protein kinases that phosphorylate raf-1 at ser-338 and ser-339.

SIGNOR-180808

Q9C0B5

P06241

0

phosphorylation

up-regulates quantity by stabilization

0.388

Our study demonstrates that under basal conditions, PSD-95 and Fyn cooperatively stabilize DHHC5 at the synaptic membrane through Fyn-mediated phosphorylation of DHHC5 at tyrosine residue 533 and the subsequent inhibition of DHHC5 association with endocytic proteins (Fig. 10).

SIGNOR-279738

Q9NV58

Q9Y6H5

1

ubiquitination

up-regulates quantity

0.453

Ubiquitylation of synphilin-1 by Dorfin. A, synphilin-1 is ubiquitylated in HEK293 cells. Several lines of evidence have suggested that derangements in the ubiquitin-proteasome protein degradation pathway may have a prominent role in the pathogenesis of PD (5). Our present study shows that Dorfin, an E3 ubiquityl ligase, is colocalized with ubiquitin in LBs of PD and physically binds to ubiquitylate synphilin-1, which is known to be a major component of LBs

SIGNOR-271455

P60484

O14641

1

dephosphorylation

down-regulates activity

0.318

This showed that while both PTEN WT and the lipid phosphatase-inactive G129E mutant suppressed phosphorylation of DVL2 on serine 143 that accumulated upon PTEN knockdown, the C124S and Y138L mutants did not .|Finally, it is important to point out that while our studies show that PTEN can directly dephosphorylate DVL2 in vitro, it is possible that regulation of serine 143 phosphorylation of DVL2 by PTEN in cells may require additional protein factors, or post-translational modifications.

SIGNOR-277035

Q96F46

P49840

0

phosphorylation

down-regulates quantity by destabilization

0.2

Glycogen synthase kinase 3 (GSK3) constitutively bound to and phosphorylated IL-17RA at T780, leading to ubiquitination and proteasome-mediated degradation of IL-17RA, thus inhibiting IL-17-mediated inflammation.

SIGNOR-277206

O15530

P04049

1

phosphorylation

up-regulates activity

0.311

PDK1, but not PKCs, phosphorylate and activate Raf1 in MAPK pathway when platelets are stimulated with 2MeSADP.

SIGNOR-280063

P05771

Q9H1D0

1

phosphorylation

down-regulates activity

0.2

This regulation requires PKC(betaII) and defined phosphorylation sites within the ARD and the C-terminus. Both regulatory sites act synergistically to constitute a novel mechanism by which ATP stabilizes channel activity and acts as a metabolic switch for Ca(2+) influx. Decreases in ATP concentration or activation of PKC(betaII) disable regulation of the channels by ATP, rendering them more susceptible to inactivation and rundown and preventing Ca(2+) overload.

SIGNOR-276265

P84243

Q14493

0

translation regulation

up-regulates quantity by expression

0.2

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

SIGNOR-265418

P06241

P17706

0

dephosphorylation

down-regulates

0.325

Previously, we reported that sfks can serve as bona fide substrates for tcptp and that tcptp dephosphorylates the y418 activation loop autophosphorylation site (corresponding to y394 in lck and y417 in fyn) to inactivate sfks

SIGNOR-177113

O15350

O00308

0

polyubiquitination

down-regulates quantity by destabilization

0.283

WWP2 ubiquitinates p73 and controls its protein stability. In our study, we identified WWP2, an E3 ligase, as a novel p73-associated protein that ubiquitinates and degrades p73. In contrast, WWP2 heterodimerizes with another E3 ligase, WWP1, which specifically ubiquitinates and degrades ΔNp73.

SIGNOR-272233

P05412

P98066

1

transcriptional regulation

up-regulates quantity by expression

0.308

Tumor necrosis factor (TNF)-stimulated gene 6 (TSG-6) encodes a protein expressed during inflammation. We have previously shown that transcription factors of the NF-IL6 and AP-1 families cooperatively modulate activation of the TSG-6 gene by TNF or interleukin 1 (IL-1) through a promoter region that contains an NF-IL6 site (-106 to -114) and an AP-1 element

SIGNOR-254052

P17612

Q04206

1

phosphorylation

up-regulates

0.516

The transcriptional activity of nf-kappa b is stimulated upon phosphorylation of its p65 subunit on serine 276 by protein kinase a (pka).

SIGNOR-58972

Q8WXG6

P20336

1

guanine nucleotide exchange factor

up-regulates activity

0.396

Rab3A, a member of the Rab3 small G protein family, regulates Ca(2+)-dependent exocytosis of neurotransmitter. The cyclical activation and inactivation of Rab3A are essential for the Rab3A action in exocytosis. GDP-Rab3A is activated to GTP-Rab3A by Rab3 GDP/GTP exchange protein (Rab3 GEP), and GTP-Rab3A is inactivated to GDP-Rab3A by Rab3 GTPase-activating protein (Rab3 GAP).

SIGNOR-265579

Q02763

P42224

1

phosphorylation

up-regulates activity

0.301

Tie2-R849W induced STAT1 phosphorylation at Y701 independent of ligand stimulation.|Together, Tie2-R849W induced functional activation of STAT1, leading to increased expression of STAT1-responsive gene like IRF1.

SIGNOR-279131

Q13586

Q8IXL6

0

phosphorylation

up-regulates activity

0.2

Similarly, STIM1 is phosphorylated on S88 by FAM20C both in vitro and in vivo.

SIGNOR-279173

Q13233

Q13546

0

phosphorylation

up-regulates activity

0.455

These findings strongly suggest that rip phosphorylates mekk1 at ser-957 and ser-994.

SIGNOR-108257

P12931

Q8IXJ6

1

phosphorylation

down-regulates quantity by destabilization

0.291

In this study, we investigated the potential regulation of SIRT2 function by c-Src. We found that the protein levels of SIRT2 were decreased by c-Src, and subsequently rescued by the addition of a Src specific inhibitor, SU6656, or by siRNA-mediated knockdown of c-Src. The c-Src interacts with and phosphorylates SIRT2 at Tyr104.

SIGNOR-263104

O43150

Q14289

0

phosphorylation

up-regulates activity

0.525

Tyrosine phosphorylation of Pap by Pyk2 or Src kinases. We have identified a new Pyk2 binding protein designated Pap. Pap is a multidomain protein composed of an N-terminal alpha-helical region with a coiled-coil motif, followed by a pleckstrin homology domain, an Arf-GAP domain, an ankyrin homology region, a proline-rich region, and a C-terminal SH3 domain. We demonstrate that Pap forms a stable complex with Pyk2 and that activation of Pyk2 leads to tyrosine phosphorylation of Pap in living cells.

SIGNOR-269704

Q9H3D4

Q96SW2

0

polyubiquitination

down-regulates quantity by destabilization

0.2

CRBN functions as a substrate receptor of the E3 ubiquitin ligase CRL4, whose substrate specificity is modulated by thalidomide and its analogs.When thalidomide binds to CRBN, substrate specificity of CRL4CRBN is altered and CRBN neomorphically binds to ∆Np63, TAp63 and other neosubstrates and ubiquitinates them for proteasomal degradation.

SIGNOR-272214

O14757

P06493

0

phosphorylation

up-regulates

0.411

Chk1 itself is also subject to cdk-mediated phosphorylation at serines 286 and 301 (s286 and 301). We show that chk1 s301 phosphorylation increases as cells progress through s and g2 and that both cdk1 and cdk2 are likely to contribute to this modification in vivo. We also find that substitution of s286 and s301 with non-phosphorylatable alanine residues strongly attenuates dna damage-induced chk1 activation and g2 checkpoint proficiency

SIGNOR-175071

Q2M2Z5

P53350

0

phosphorylation

up-regulates

0.519

Here, we identify a novel centrosomal substrate of plk1, kizuna (kiz), depletion of which causes fragmentation and dissociation of the pericentriolar material from centrioles at prometaphase, resulting in multipolar spindles. Plk1 maintains the integrity of the spindle poles by phosphorylating kiz.

SIGNOR-149630

P11678

P13727

1

post translational modification

up-regulates activity

0.434

Human eosinophils are bone marrow-derived, non-dividing granulocytes of the innate immune system, which store the highly cationic proteins eosinophil peroxidase (EPO), major basic protein (MBP), eosinophil-derived neurotoxin (EDN), and eosinophil cationic protein (ECP) in secondary granules. we demonstrated that Tyr nitration of the eosinophil granule proteins is exclusively mediated by EPO, in the presence of functional NADPH oxidase and minute amounts of NOx. EPO appears to nitrate itself via an autocatalytic mechanism.

SIGNOR-261703