GleghornLab/Signor_2class · Datasets at Hugging Face

IdA string	IdB string	labels int64	mechanism string	effect string	score float64	sentence string	signor_id string
P68400	Q2V2M9	1	phosphorylation	down-regulates	0.309	We have identified a novel striated muscle-specific splice variant of the formin fhod3 that introduces a casein kinase 2 (ck2) phosphorylation site. The specific targeting of muscle fhod3 to the myofibrils in cardiomyocytes is abolished in phosphomutants or by the inhibition of ck2. Phosphorylation of muscle fhod3 also prevents its interaction with p62/sequestosome 1 and its recruitment to autophagosomes.	SIGNOR-170525
Q96GD4	P08670	1	phosphorylation	down-regulates	0.423	By identifying eight aurora-b phosphorylation sites on vimentin in vitro, we have demonstrated that vimentin-ser-72 is an in vitrophosphorylation site of aurora-b. in vitro analyses revealed that aurora-b phosphorylates vimentin at approximately 2 mol phosphate/mol of substrate for 30 min and that this phosphorylation dramatically inhibits vimentin filament formation.	SIGNOR-96057
P60484	Q15831	0	phosphorylation	down-regulates activity	0.604	The C-terminal tail of PTEN is also the target of mutations in tumors. As mentioned, this region contains the main phosphorylation sites mapped to residues Ser362, Thr366, Ser370, Ser380, Thr382, Thr383, and Ser385, and the kinases involved are casein kinase 2 (CK2), GSK3_, LKB1, and MAST.84,97-101 The phosphorylation of the tail has been shown to enhance PTEN stability but at the same time decrease its phosphatase activity	SIGNOR-161118
P53805	Q14469	0	transcriptional regulation	down-regulates quantity by repression	0.2	Increased Calcineurin/NFAT activity by Notch signaling involves downregulation of Calcipressin, an endogenous Calcineurin inhibitor, through a HES-1-dependent mechanism .... Chromatin immunoprecipitation (ChIP) analysis of keratinocytes overexpressing HES-1 showed that this protein can bind to the HES binding sites present in both distal and proximal promoters	SIGNOR-252026
O00159	P49841	0	phosphorylation	up-regulates activity	0.2	Here, we report that at early G1 the glycogen synthase kinase 3\u03b2 phosphorylates and stabilizes Nuclear myosin 1c, allowing for Nuclear myosin 1c association with the chromatin.	SIGNOR-279184
Q96T60	P78527	0	phosphorylation	up-regulates	0.649	We demonstrate that pnkp is phosphorylated by the dna-dependent protein kinase (dna-pk) and ataxia-telangiectasia mutated (atm) in vitro. The major phosphorylation site for both kinases was serine 114, with serine 126 being a minor site. Purified pnkp protein with mutation of serines 114 and 126 had decreased dna kinase and dna phosphatase activities and reduced affinity for dna in vitro.	SIGNOR-176020
P10828	P28482	0	phosphorylation	down-regulates activity	0.412	We concluded that serine 142 of the tr dbd is the likely site of phosphorylation by t(4)-activated mapk and that the docking site on tr for activated mapk includes residues 128-133 (kgffrr), a basic amino acid-enriched motif novel for mapk substrates. Tr mutations in the proposed mapk docking domain and at residue 142 modulated t(4)-conditioned shedding of co-repressor and recruitment of co-activator proteins by the receptor, and they altered transcriptional activity of tr in a thyroid hormone response element-luciferase reporter assay.	SIGNOR-102216
Q13627	P01106	1	phosphorylation	down-regulates quantity	0.374	We also found that DYRK1A phosphorylated c-Myc on Ser62, priming phosphorylation on Thr58 by GSK3\u03b2 and subsequent degradation.\|c-Myc expression is down-regulated by DYRK1A.	SIGNOR-279609
P08908	Q5T0F9	0	transcriptional regulation	down-regulates quantity by repression	0.335	Human Freud-2/CC2D1B: a novel repressor of postsynaptic serotonin-1A receptor expression\|Human Freud-2 showed strong repressor activity at the human 5-HT1A or heterologous promoter in human HEK-293 5-HT1A-negative cells and neuronal SK-N-SH cells, a model of postsynaptic 5-HT1A receptor-positive cells.	SIGNOR-268298
Q6P4F7	P61586	1	gtpase-activating protein	down-regulates activity	0.549	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-260466
Q9NY65	Q5SQI0	0	acetylation	up-regulates quantity by stabilization	0.244	Alpha-Tubulin acetyltransferase (alphaTAT1) is the major α-tubulin lysine-40 (K40) acetyltransferase in mammals, nematodes, and protozoa, and its activity plays a conserved role in several microtubule-based processes.\|The tubulin subunits of microtubules are acetylated, and lysine-40 (K40) of the alpha-tubulin subunit has been identified as an important conserved site of microtubule acetylation (6–8). This modification is considered a hallmark of stable, long-lived microtubules	SIGNOR-272250
Q16625	P05771	0	phosphorylation	up-regulates activity	0.455	Protein kinase C regulates the phosphorylation and cellular localization of occludin. Ser(338) of occludin was identified as an in vitro protein kinase C phosphorylation site using peptide mass fingerprint analysis and electrospray ionization tandem mass spectroscopy. Both the phosphorylation of occludin and its incorporation into tight junctions induced by calcium switch were markedly inhibited by the PKC inhibitor GF-109203X.	SIGNOR-249106
P10451	Q8IXL6	0	phosphorylation	down-regulates quantity	0.683	OPN phosphorylation by Fam20C decreased OPN secretion, and OPN neutralization reduced Fam20C-deficiency-induced osteoclast differentiation and bone metastasis.	SIGNOR-278936
Q8TDC3	Q15831	0	phosphorylation	up-regulates	0.485	Lkb1 is a master kinase that activates 13 kinases of the ampk subfamily, including mark/par-1we recently demonstrated that the lkb1 tumour suppressor kinase, in complex with the pseudokinase strad and the scaffolding protein mo25, phosphorylates and activates amp-activated protein kinase (ampk). A total of 12 human kinases (nuak1, nuak2, brsk1, brsk2, qik, qsk, sik, mark1, mark2, mark3, mark4 and melk) are related to ampk. Here we demonstrate that lkb1 can phosphorylate the t-loop of all the members of this subfamily, apart from melk, increasing their activity >50-fold	SIGNOR-122413
P08151	Q6PHR2	0	phosphorylation	up-regulates activity	0.673	We show that ULK3 is able to phosphorylate three mammalian GLI proteins in vitro. \| Our data suggest that serine/threonine kinase ULK3 is involved in the SHH pathway as a positive regulator of GLI proteins.	SIGNOR-260797
P63000	O14827	0	guanine nucleotide exchange factor	up-regulates activity	0.498	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-260574
Q69YH5	Q96GD4	0	phosphorylation	down-regulates activity	0.446	This result demonstrates that the three sites of Repo-Man (Ser-543, Ser-977, and Ser-981) are phosphorylated by Aurora B in early mitosis. We uncover that PP1γ is recruited to mitotic chromosomes by its regulatory subunit Repo-Man in the absence of Aurora B activity and that Aurora B regulates dissociation of PP1γ by phosphorylating and disrupting PP1γ-Repo-Man interactions on chromatin.	SIGNOR-274001
P49759	Q96I25	1	phosphorylation	up-regulates activity	0.317	In this work, we show that Cdc2-like kinase 1 (Clk1) phosphorylates SPF45 on eight serine residues.	SIGNOR-262710
Q15349	P28482	0	phosphorylation	up-regulates	0.717	Erk-activates the rsk family of serine/threonine kinases,rsk1, rsk2, and rsk3.	SIGNOR-161515
P50053	P60891	1	phosphorylation	up-regulates activity	0.348	Ketohexokinase-A (KHK-A; also known as fructokinase-A) phosphorylates PRPS1 T225 and activates PRPS1 by blocking the binding of ADP, AMP, and GDP, which is required for hepatocellular carcinoma development	SIGNOR-265735
P35354	P15172	1	null	up-regulates	0.264	Furthermore, COX-2 inhibition reduced MyoD expression in regenerating muscle, suggesting a role for COX-2 in modulating muscle differentiation, as well as growth	SIGNOR-256214
Q9NQU5	P15976	1	phosphorylation	up-regulates activity	0.2	In addition, PAK5 knockdown also markedly reduced the association of GATA1 with HDAC3/4.\|PAK5 phosphorylates the transcription factor GATA1 mainly at Ser161 and Ser 187, phosphorylated GATA1 recruits more HDAC3/4 to the promoter of E-cadherin and consequently suppresses the transcription of E-cadherin gene and promotes the EMT of breast cancer cells.	SIGNOR-278415
P52564	P19525	0	phosphorylation	up-regulates activity	0.2	Consistent with this observation, PKR was capable of activating MKK6 as assessed in a coupled kinase assay containing the components of the p38 MAPK pathway.\|In vitro kinase assays revealed that MKK6 was efficiently phosphorylated by PKR, and this could be inhibited by 2-aminopurine.	SIGNOR-279707
P08238	P12931	0	phosphorylation	up-regulates	0.587	C-src directly phosphorylates hsp90 on tyrosine 300 residue and that this event is essential for vegf-stimulated enos association to hsp90 and thus no release from endothelial cells.	SIGNOR-157781
Q9UNE7	Q06787	1	ubiquitination	down-regulates quantity by destabilization	0.387	The results showed that FMR1 was ubiquitinated by CHIP WT or CHIP K30A. Also, ubiquitinated FMR1 accumulated in the presence of MG132, indicating that CHIP ubiquitinates FMR1 for proteasomal degradation ( Fig. 3 B).	SIGNOR-278599
P01137	P08047	0	transcriptional regulation	up-regulates quantity by expression	0.296	MAPKs have cis-acting regulatory elements in the mouse-TGF promoter region, which respond to various transcription factors, including specificity protein-1 and activating protein 1. Thus, it is possible that apoptotic cell-induced TGF-β mRNA expression is mediated through activation of these transcription factors via MAPK signaling. Xiao et al. reported that all of the MAPK members, including p38/ERK/JNK, are required for apoptotic Jurkat cells up-regulation of TGF-β production	SIGNOR-251740
Q13627	O75688	0	dephosphorylation	down-regulates activity	0.236	In conclusion, our study demonstrates that DYRK1A autophosphorylates Ser258, the dephosphorylation target of PPM1B, and PPM1B negatively regulates DYRK1A activity.\|We found that PPM1B dephosphorylates DYRK1A at Ser258, contributing to the inhibition of DYRK1A activity.	SIGNOR-277108
P24941	Q12834	1	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
Q16236	Q92626	1	transcriptional regulation	up-regulates quantity by expression	0.2	PXDN expression in response to H2O2 and the Nrf2-specific inducers, tert-butylhydroquinone (tBHQ) and sulforaphane (SFN), was determined by western blotting and immunofluorescence microscopy, in HeLa and HEK293 cells.We found that Nrf2 binds to and increases luciferase reporter gene expression from the PXDN promoter via a putative Nrf2-binding site. In summary, we show that PXDN is a novel target of the redox sensitive transcription factor Nrf2.	SIGNOR-265248
Q3KR16	P53350	0	phosphorylation	up-regulates	0.415	We reported previously that a guanine nucleotide exchange factor, myogef, localizes to the central spindle, activates rhoa, and is required for cytokinesis. In this study, we have found that plk1 (polo-like kinase 1) can phosphorylate myogef, thereby recruiting myogef to the central spindle as well as enhancing myogef activity toward rhoa. The in vitro kinase assay shows that plk1 can phosphorylate myogef on threonine 574.	SIGNOR-179954
Q969R5	O76064	0	ubiquitination	up-regulates activity	0.242	L3MBTL2 links RNF8 and RNF168 in the DNA double strand break response. The protein kinase ATM phosphorylates L3MBTL2, which recruits it to the DNA lesion by promoting the interaction between MDC1 and L3MBTL2. L3MBTL2 is subsequently ubiquitinated by RNF8, which acts as a docking site for RNF168, thereby recruiting the ubiquitin ligase to the damage site. RNF168, in turn, ubiquitinates H2A-type histones to amplify the DNA damage response and recruit downstream DNA repair proteins for proper DSB signaling.	SIGNOR-266787
P69905	P09601	0	null	down-regulates activity	0.253	Heme oxygenase (HO), by catabolizing heme to bile pigments, down-regulates cellular hemoprotein, hemoglobin, and heme	SIGNOR-251813
Q9H9Z2	P01344	1	translation regulation	up-regulates quantity by expression	0.397	Lin-28 binds IGF-2 mRNA and participates in skeletal myogenesis by increasing translation efficiency	SIGNOR-277339
Q05397	P24844	1	phosphorylation	up-regulates activity	0.286	It indicates that FAK positively regulates the phosphorylation of MLC2.	SIGNOR-280098
P07948	Q9UK17	1	phosphorylation	up-regulates activity	0.2	These results indicate that Y108 (for Src-family kinases) and Y136 (for EGFR kinase) are involved in the tyrosine phosphorylation of hKv4.3 channels.	SIGNOR-276395
Q8NHM5	Q99814	0	transcriptional regulation	up-regulates quantity by expression	0.2	To this end, we confirm that KDM3A, KDM4B, KDM4C, KDM5B, KDM5C, and KDM62 are direct targets of HIF-1a while extent the list of known targets to KDM2A, KDM2B, KDM4D, KDM5A, and KDM6A. The results demonstrated that majority of the KDMs were similarly induced (KDM2A, KDM2B, KDM3A, KDM4B, KDM4C, KDM4D, KDM5A, KDM5B, KDM5C, KDM6B, and KDM7A) or repressed (KDM NO66 and KDM1A) by both HIF-1a and HIF-2a.	SIGNOR-271582
P12830	Q15139	0	phosphorylation	up-regulates	0.451	Our study has identified e-cadherin as a novel substrate of pkd1, and phosphorylation of e-cadherin by pkd1 is associated with increased cellular aggregation and decreased cellular motility in prostate cancer.	SIGNOR-133856
P68363	Q8NG68	0	tyrosination	down-regulates	0.46	Tubulin tyrosine ligase (ttl) adds a c-terminal tyr to __tubulin as part of a tyrosination/detyrosination cycle present in most eukaryotic cells. / ttl inhibits spontaneous tubulin polymerization	SIGNOR-176915
Q969H0	P23769	1	ubiquitination	down-regulates quantity by destabilization	0.388	Here, we demonstrate that F-box/WD repeat-containing protein 7 (Fbw7/Fbxw7), a component of Skp1, Cullin 1, F-box-containing complex (SCF)-type E3 ligase, is an E3 ligase for GATA2. GATA2 contains a cell division control protein 4 (Cdc4) phosphodegron (CPD), a consensus motif for ubiquitylation by Fbw7, which includes Thr(176). Ectopic expression of Fbw7 destabilized GATA2 and promoted its proteasomal degradation.	SIGNOR-256005
O00418	P54646	0	phosphorylation	up-regulates activity	0.498	Stimulation of the AMP-activated Protein Kinase Leads to Activation of Eukaryotic Elongation Factor 2 Kinase and to Its Phosphorylation at a Novel Site, Serine 398. phosphorylation of eEF2 kinase at Ser-398 leads to an increase in its activity.	SIGNOR-250158
P10914	Q14164	0	phosphorylation	down-regulates activity	0.35	We demonstrated that IKK-ε phosphorylated the transcription factor IFN regulatory factor 1 (IRF-1) at amino acid (aa) 215/219/221 in primary CD4(+) T cells and blocked its transcriptional activity.	SIGNOR-276480
Q13315	Q5XUX0	1	phosphorylation	up-regulates	0.406	We find that dna damage induced by gamma-irradiation results in increased fbxo31 levels, which requires phosphorylation of fbxo31 by the ddr-initiating kinase atm	SIGNOR-185635
Q99961	P12931	0	phosphorylation	down-regulates	0.639	Further, we identified an interaction between fak's second pro-rich motif and endophilin a2's sh3 domain. This interaction served as an autophosphorylation-dependent scaffold to allow src phosphorylation of endophilin a2 at tyr315. Tyr315 phosphorylation inhibited endophilin/dynamin interactions, and blockade of tyr315 phosphorylation promoted endocytosis of mt1-mmp. Together, these results suggest a regulatory mechanism of cell invasion whereby fak promotes cell-surface presentation of mt1-mmp by inhibiting endophilin a2-dependent endocytosis.	SIGNOR-139150
P55072	Q16827	0	dephosphorylation	down-regulates activity	0.423	An important aspect of this study is that tyrosine dephosphorylation of VCP by PTPRO sensitizes HepG2 cells to Doxorubicin, a chemotherapeutic drug commonly used for a variety of cancers.	SIGNOR-277063
Q13200	Q92918	0	phosphorylation	up-regulates activity	0.2	Seven of these kinases (PIM1/2/3, MAP4K1/2, PKA, and NEK6) directly and robustly phosphorylated recombinant GST-Rpn1 at S361 in vitro (Fig. 3D and SI Appendix, Fig. S3 A and B).	SIGNOR-273899
Q99814	P28482	0	phosphorylation	up-regulates quantity by stabilization	0.25	The activation of ERK1/2 upon hypoxia promoted HIF-2alpha phosphorylation, enhancing its interaction with USP33.Here, we identified USP33 as essential deubiquitinase that stabilizes HIF-2alpha protein in an ERK1/2-dependent manner to promote hypoxia response in cancer cells.	SIGNOR-277585
Q99538	Q9Y4K3	0	polyubiquitination	up-regulates quantity by stabilization	0.307	We demonstrate that TRAF6 ubiquitinates the proform of AEP through K63-linked polyubiquitin, reversible by USP17, and forms a complex with HSP90α to subsequently promote pro-AEP intracellular stability as well as secretion. We now present evidence that AEP is a substrate for TRAF6 ubiquitination, resulting in AEP/TRAF6/HSP90α complex formation.	SIGNOR-272853
Q8NG27	P84022	1	ubiquitination	down-regulates activity	0.391	In summary, these results indicated that PJA1 promotes the ubiquitination of phosphorylated SMAD3, resulting in reduced activity of a TGF-\u03b2/SMAD3/\u03b22SP-dependent tumor-suppressing pathway in HCC cells ( xref ).	SIGNOR-278832
Q9H461	Q9ULT6	0	ubiquitination	down-regulates quantity	0.539	Here we show that the cell-surface transmembrane E3 ubiquitin ligase zinc and ring finger 3 (ZNRF3) and its homologue ring finger 43 (RNF43) are negative feedback regulators of Wnt signalling. ZNRF3 is associated with the Wnt receptor complex, and inhibits Wnt signalling by promoting the turnover of frizzled and LRP6.	SIGNOR-260111
P01019-PRO_0000420660	Q9BYF1	0	cleavage	up-regulates quantity	0.2	At first, ACE2 has been demonstrated to induce conversion of Ang I into Ang (1–7) by means of intermediate production of Ang (1–9), a fragment with unknown function.	SIGNOR-260227
Q04759	Q5JVS0	1	phosphorylation	down-regulates activity	0.303	We found a strong phosphorylation of Ki-1/57 by PKCalphabeta, PKCdelta, PKClambda/zeta, and especially by PKCsigma, however not by PKCmi. These data show that Ki-1/57 can serve in principal as a substrate for a wide variety of different PKC isoforms but also that its phosphorylation is strongest with PKCsigma. \| This suggests that the two threonine residues present in this fragment (Thr354 and Thr375) might be the main target residues for phosphorylation by PKC in vitro. \| Ki-1/57 Exits the Nucleus upon PMA Activation	SIGNOR-249256
Q76N32	Q96SN8	1	relocalization	up-regulates activity	0.452	We also found that Cep68 forms a complex with Cep215 (also known as Cdk5Rap2) and PCNT (also known as pericentrin), two PCM (pericentriolar material) proteins involved in centriole engagement. \|Retention of Cep68 or PCNT in late mitosis prevents the removal of Cep215	SIGNOR-275624
P01100	P11511	1	transcriptional regulation	up-regulates quantity by expression	0.346	We found that both SF1 and LRH1 can transcriptionally cooperate with the AP-1 family members c-JUN and c-FOS, known to be associated with enhanced proliferation of endometrial carcinoma cells, to further enhance activation of the STAR, HSD3B2, and CYP19A1 PII promoters.	SIGNOR-254879
P38398	O75367	1	ubiquitination	up-regulates activity	0.2	BRCA1 Ubiquitinates K123 of mH2A1 in a Ligase-Activity-Dependent Manner.	SIGNOR-278752
P06493	Q16635	1	phosphorylation	down-regulates quantity by destabilization	0.266	Our studies suggest that phosphorylation and degradation of TAZ by Cdk1 may play important roles in apoptosis induced by antitubulin drugs.	SIGNOR-278240
P08100	Q15835	0	phosphorylation	up-regulates activity	0.923	That light-dependent phosphorylation of Rho is mediated primarily by RK. Addition of an inhibitory antibody against rhodopsin kinase (RK) lowered phosphorylation at Ser334, Ser338, and Ser343, without changing the ratio between phosphorylation sites. upon illumination, Ser334c, Ser338, and Ser343 are phosphorylated.	SIGNOR-251190
Q15424	P35637	1	relocalization	up-regulates activity	0.363	SAFB1 as well as Matrin3 to regulate splicing and ligand-mediated transcription\| In addition, depletion of SAFB1 reduced FUS's localization to chromatin-bound fraction and splicing activity, suggesting SAFB1 could tether FUS to chromatin compartment thorough N-terminal DNA-binding motif.	SIGNOR-262821
Q13131	Q13554	0	phosphorylation	up-regulates	0.2	These data indicate that the camkks function in intact cells as ampkks, predicting wider roles for these kinases in regulating ampk activity in vivo.	SIGNOR-138360
Q96GD4	O14578	1	phosphorylation	down-regulates activity	0.283	Finally, Aurora B phosphorylates CIT-K to control its localization and interaction with central spindle partners.\|Together these findings indicate that CIT-K is an Aurora B substrate and that Aurora B phosphorylation at S699 dampens the association of CIT-K with KIF23 and the chromosomal passenger complex in order to reduce CIT-K accumulation at the spindle midzone in early cytokinesis.	SIGNOR-279140
Q12926	O14672	1	post transcriptional regulation	up-regulates quantity	0.2	Neuronal ELAV (nELAV) proteins are RNA-binding proteins which play a physiological role in controlling gene expression in memory formation, and their alteration may contribute to cognitive impairment associated with neurodegenerative pathologies such as Alzheimer's disease (AD). The experiments show for the first time that ADAM10mRNA represents a nELAV target and that these RNA-binding proteins can play a role in the post-transcriptional regulation of ADAM10 expression. nELAV proteins specifically bind the ADAM10 mRNA and this binding is disrupted following Aβ exposure	SIGNOR-266863
P17612	P19174	1	phosphorylation	down-regulates	0.2	The observation that pka also phosphorylates plc-yl on serine 1248 suggests that phosphorylation of this residue may be a common mechanism by which pkc and pka inhibit plc-yl.	SIGNOR-17901
Q13424	P53778	0	phosphorylation	up-regulates	0.668	Sapk3 phosphorylates alpha1-syntrophin at serine residues 193 and 201 in vitro and phosphorylation is dependent on binding to the pdz domain of alpha1-syntrophin. The finding that sapk3 co-localizes with _1-syntrophin in skeletal muscle, that it binds to the pdz domain of _1-syntrophin, and that phosphorylation of _1-syntrophin depends on this interaction identifies a novel mechanism for targeting a protein kinase to its substrates.	SIGNOR-67061
Q16236	Q9UPY5	1	transcriptional regulation	up-regulates quantity by expression	0.424	NFE2L2 is stabilized and translocates to the nucleus, where it dimerizes with sMAF proteins. This complex binds to AREs to mediate the transcription of genes involved in iron metabolism, GSH metabolism, and ROS detoxification. NFE2L2 directly binds to the promoter region of SLC7A11, leading to increased expression of this transporter, which in turn contributes to the resistance to ferroptosis and to radiotherapy	SIGNOR-279867
Q9UJV9	Q06187	0	phosphorylation	up-regulates activity	0.406	The kinase and SH3/SH2 interaction domains of BTK bind, respectively, the DEAD-box domain of DDX41 and transmembrane region of STING. BTK phosphorylates DDX41, and its kinase activities are critical for STING-mediated IFN-β production. We show that Tyr364 and Tyr414 of DDX41 are critical for its recognition of AT-rich DNA and binding to STING, and tandem mass spectrometry identifies Tyr414 as the BTK phosphorylation site.	SIGNOR-266404
Q12888	Q15759	0	phosphorylation	down-regulates activity	0.2	Here we show that 53BP1 is phosphorylated during mitosis on two residues, T1609 and S1618, located in its well-conserved ubiquitination-dependent recruitment (UDR) motif.\|Dephosphorylation enables the recruitment of 53BP1 to double-strand DNA breaks \|phosphorylation of T1609 is likely to be mediated by p38 MAPK	SIGNOR-264447
P49593	Q14012	1	dephosphorylation	down-regulates activity	0.461	Calmodulin-dependent protein kinase phosphatase (CaMKP) dephosphorylates and concomitantly deactivates multifunctional Ca(2+)/calmodulin-dependent protein kinases , such as CaMKI, CaMKII, and CaMKIV.	SIGNOR-277111
P78352	P35637	0	post transcriptional regulation	up-regulates quantity	0.27	These results point toward a novel mechanism by which FUS targets neuronal mRNA and given that these PSD-95 and Shank1 3'-UTR G quadruplex structures are also targeted by the fragile X mental retardation protein (FMRP), they raise the possibility that FUS and FMRP might work together to regulate the translation of these neuronal mRNA targets.\|As seen in Figure 7 (top panel), both PSD-95 Q1-Q2 and Shank1a GQ probes pulled down endogenous FUS, whereas their M2 mutants did not, indicating that the GQ structure is sufficient for recognition.	SIGNOR-262103
P49841	Q05516	1	phosphorylation	up-regulates activity	0.2	Taken together, we conclude that S184 and T282 of ZBTB16 may be phosphorylated by GSK3beta in cells under serum starvation condition.	SIGNOR-279618
Q16539	Q15717	1	phosphorylation	up-regulates	0.523	P38 mapk phosphorylates the mrna binding protein hur on thr118, which results in cytoplasmic accumulation of hur and its enhanced binding to the p21cip1 mrna.	SIGNOR-186135
Q15139	P61073	1	phosphorylation	down-regulates quantity	0.2	Inhibition of PKD activity restores membrane expression of CXCR4 and migration towards CXCL12 in BCR responsive cells in vitro.\|This cascade consisted on a novel BCR dependent pathway in which PI3K-delta phosphorylates PKD, which in turn phosphorylates CXCR4 at Ser 324/325.	SIGNOR-279263
P28482	P33076	1	phosphorylation	up-regulates	0.432	We show in this study that the nuclear localized form of ciita is a predominantly phosphorylated form of the protein, whereas cytoplasmic ciita is predominantly unphosphorylated. Novel phosphorylation sites were determined to be located within a region that contains serine residues 286, 288, and 293. Double mutations of these residues increased nuclear ciita, indicating that these sites are not required for nuclear import. Erk1/2-mediated phosphorylation of ciita down-regulates ciita activity by priming it for nuclear export, thus providing a means for cells to tightly regulate the extent of antigen presentation.	SIGNOR-160609
O95999	Q96J02	0	ubiquitination	down-regulates quantity by destabilization	0.276	The HECT domain ubiquitin ligases NEDD4 and Itch promote ubiquitination and degradation of Bcl10, thus downmodulating NF-kappa B activation.	SIGNOR-271414
P84103	O15355	0	dephosphorylation	down-regulates activity	0.2	Here, we found that the PPM1G regulated SRSF3, and high levels of PPM1G decreased SRSF3 activity in HCC cells.\|PPM1G interacted with SRSF3 and dephosphorylated SRSF3.	SIGNOR-277048
Q16584	P31749	0	phosphorylation	down-regulates	0.4	Negative regulation of mixed lineage kinase 3 by protein kinase b/akt leads to cell survivalthe expression of activated akt1 inhibits mlk3-mediated cell death in a manner dependent on serine 674 phosphorylation.	SIGNOR-252592
Q9H2D6	P53350	0	phosphorylation	up-regulates	0.335	Here we show that tara is a novel polo-like kinase 1 (plk1) target protein. Plk1 interacts with and phosphorylates tara in vivo and in vitro. Actually, the thr-457 in tara was a bona fide in vivo phosphorylation site for plk1. Interestingly, we found that the centrosomal localization of tara depended on the thr-457 phosphorylation and the kinase activity of plk1	SIGNOR-198353
P01111	Q07889	0	guanine nucleotide exchange factor	up-regulates activity	0.78	Sos and Ras-GRF are two families of guanine nucleotide exchange factors that activate Ras proteins in cells. Sos proteins are ubiquitously expressed and are activated in response to cell-surface tyrosine kinase stimulation Sos1 and Ras-GRF1 activate the Ras proteins Ha-Ras, N-Ras, and Ki-Ras	SIGNOR-110566
Q99816	Q6UWE0	0	monoubiquitination	down-regulates quantity	0.527	Tal increases ubiquitylation of Tsg101 and affects its solubility in a RING- and PTAP-dependent manner. Tal-mediated ubiquitylation of Tsg101 inactivates this sorting function and concomitantly translocates Tsg101 from relatively insoluble membrane subdomains. Presumably, the coordinated action of Tal and a deubiquitylation enzyme (DUB) enables recycling of Tsg101 and reloading of cargo.	SIGNOR-271509
Q13188	Q9H8S9	1	phosphorylation	up-regulates	0.85	Mob1, which forms a complex with lats1/2, is also phosphorylated by mst1/2, resulting in an enhanced lats1/2 mob1 interaction.	SIGNOR-175809
O15409	P78509	1	transcriptional regulation	up-regulates quantity by expression	0.365	By interacting with CASK, TBR1 regulates several ASD candidate genes, such as GRIN2B, AUTS2 and RELN—all of which are recurrently mutated in ASD. In areas of the brain with overlapping expression patterns, such as in glutamatergic layer 6 neurons, the TBR1–FOXP2 interaction may result in co-ordinated regulation of common downstream targets.	SIGNOR-266833
P60891	Q9NRM7	0	phosphorylation	down-regulates quantity by destabilization	0.2	Recruitment of TRAF2 to PRPS1/2 requires phosphorylation of PRPS1 S285 or PRPS2 T285, which is mediated by low stiffness-activated large tumor suppressor (LATS)1/2 kinases.LATS1/2-dependent S/T285 phosphorylation is required for PRPS1/2 ubiquitination and degradation at low stiffness.	SIGNOR-276504
Q9Y6K9	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-266743
P05129	P11388	1	phosphorylation	up-regulates activity	0.359	Here, we have shown that the enzymatic activity of topoisomerase II alpha protein purified from HeLa cell nuclei was strongly enhanced following phosphorylation by protein kinase C. \| Site-directed mutagenesis studies indicated that phosphorylation of serine 29 generated both of these phosphopeptides.	SIGNOR-249196
P54646	Q96RR4	0	phosphorylation	up-regulates	0.619	These data indicate that the camkks function in intact cells as ampkks, predicting wider roles for these kinases in regulating ampk activity in vivo.	SIGNOR-138364
Q9BXL7	P31749	0	phosphorylation	up-regulates activity	0.522	Akt phosphorylates S637 and S645 in the linker region of Carma1	SIGNOR-276621
P40763	P28827	0	dephosphorylation	down-regulates activity	0.262	Thus PTPRM suppresses STAT3 signaling in DDIAS-knockdown cells, suggesting that DDIAS promotes the IL-6\u2013mediated STAT3 signaling in malignant cancer cells by inhibiting the PTPRM function.\|We report that PTPRM is a novel STAT3 tyrosine phosphatase and that it negatively regulates STAT3 activation by dephosphorylating Y705 of STAT3 in the presence of IL-6.	SIGNOR-277016
Q12879	P12931	0	phosphorylation	up-regulates activity	0.567	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-247167
Q02577	Q96EB6	0	deacetylation	up-regulates activity	0.383	SIRT1 deacetylates the brain-specific helix-loop-helix transcription factor NHLH2 on lysine 49 to increase its activation of the MAO-A promoter	SIGNOR-254830
P56945	Q15678	0	dephosphorylation	down-regulates	0.394	We show that p130 crk-associated substrate (p130cas) is a direct substrate of ptpn14 and that ptpn14 specifically regulates p130cas phosphorylation at tyrosine residue 128 (y128) in colorectal cancer (crc) cells. We engineered crc cells homozygous for a p130cas y128f knock-in mutant and found that these cells exhibit significantly reduced migration and colony formation	SIGNOR-197923
O15524	P07948	0	phosphorylation	down-regulates activity	0.301	These findings show that SOCS1 phosphorylation by the SRC family inhibits its tumor-suppressive activity, indicating that patients with increased SOCS1 phosphorylation may benefit from SRC family kinase inhibitors.	SIGNOR-277888
Q9UNE7	Q01860	1	ubiquitination	down-regulates quantity by destabilization	0.303	CHIP overexpression decreased OCT4 stability through proteasomal degradation.\|CHIP E3 ligase ubiquitinates OCT4 at lysine 284.\|These data suggest that CHIP induces OCT4 ubiquitination and degradation.	SIGNOR-278562
P35558	P46379	0	acetylation	down-regulates quantity by destabilization	0.34	These results indicate that BAT3 and P300 can both exist in the PEPCK1 protein complex, suggesting the possibility that BAT3 could be an enhancer of PEPCK1 acetylation. \| indicating a synergistic effect of BAT3 and P300 to promote PEPCK1 acetylation.	SIGNOR-267598
P29475	Q15139	0	phosphorylation	up-regulates activity	0.385	In addition, we demonstrate that protein kinase D1 activates nNOS by phosphorylating the activatory residue Ser1412, leading to increased \u00b7NO production, hence establishing a novel role of PKD in the regulation of \u00b7NO synthesis.\|PKD1 phosphorylates nNOS at activatory Ser 1412 in vitro and in live cells.	SIGNOR-278426
P31995	P06241	0	phosphorylation	up-regulates activity	0.2	Fyn and Blk definitely phosphorylate Y-282 in the ITAM of FcgRIIa/c, whereas the non-ITAM tyrosine residue (Y-275) becomes phosphorylated by Syk, as the phosphorylation of double point mutants shows. In addition to these tyrosine residues, Fyn, Blk, and Syk might phosphorylate the most C-terminal tyrosine residue (Y-298) because altering this tyrosine residue together with one of the tyrosine residues clearly shown to be phosphorylated by the respective PTK results in the abrogation of phosphorylation	SIGNOR-262677
P78317	P08047	1	polyubiquitination	down-regulates quantity by destabilization	0.39	Here, we identified RNF4 as the ubiquitin E3 ligase of Sp1. From in vitro and in vivo experiments, we found that sumoylated Sp1 can recruit RNF4 as a ubiquitin E3 ligase that subjects sumoylated Sp1 to proteasomal degradation.	SIGNOR-272720
Q13490	Q9Y572	1	polyubiquitination	up-regulates activity	0.677	CIAP1/2 are direct E3 ligases conjugating diverse types of ubiquitin chains to receptor interacting proteins kinases 1 to 4 (RIP1-4).Together, our results demonstrate that depleting cIAP1/2 inhibits RIP1-4 mediated NF-kB activation without affecting RIP auto-phosphorylation.	SIGNOR-272711
Q00987	Q01130	0	transcriptional regulation	up-regulates quantity by expression	0.279	Using MDM2 P1 and P2 promoter-reporter systems, we screened clones regulating MDM2 transcriptions in a p53-independent manner by overexpression. Nine clones from the screening library showed enhanced MDM2 promoter activity and MDM2 expression in p53-deficient HCT116 cells. Among them, six clones, including NTRK2, GNA15, SFRS2, EIF5A, ELAVL1, and YWHAB mediated MAPK signaling for expressing MDM2.	SIGNOR-260076
Q9BY84	Q16539	1	dephosphorylation	down-regulates	0.805	Mkp-7 binds to and inactivates p38 mapk and jnk/sapk, but not erk inhibited by dual specificity phosphatases, such as dusp1, dusp10, and dusp16(uniprot)	SIGNOR-108233
P21675	P04637	1	phosphorylation	down-regulates	0.681	Phosphorylation on thr-55 by taf1 mediates degradation of p53	SIGNOR-123651
P31749	P15976	1	phosphorylation	up-regulates	0.514	We found that akt directly phosphorylates the transcription factor gata-1 at serine 310 and that this site-specific phosphorylation is required for the transcriptional activation of the timp-1 promoter.	SIGNOR-139782
Q9H2K2	O15169	1	ADP-ribosylation	down-regulates quantity by destabilization	0.705	Together, these findings are consistent with the hypothesis that TNKS promotes the ubiquitination and degradation of axin, which may be mediated, at least in part, through the direct PARsylation of axin.	SIGNOR-263378

P68400

Q2V2M9

1

phosphorylation

down-regulates

0.309

We have identified a novel striated muscle-specific splice variant of the formin fhod3 that introduces a casein kinase 2 (ck2) phosphorylation site. The specific targeting of muscle fhod3 to the myofibrils in cardiomyocytes is abolished in phosphomutants or by the inhibition of ck2. Phosphorylation of muscle fhod3 also prevents its interaction with p62/sequestosome 1 and its recruitment to autophagosomes.

SIGNOR-170525

Q96GD4

P08670

1

phosphorylation

down-regulates

0.423

By identifying eight aurora-b phosphorylation sites on vimentin in vitro, we have demonstrated that vimentin-ser-72 is an in vitrophosphorylation site of aurora-b. in vitro analyses revealed that aurora-b phosphorylates vimentin at approximately 2 mol phosphate/mol of substrate for 30 min and that this phosphorylation dramatically inhibits vimentin filament formation.

SIGNOR-96057

P60484

Q15831

0

phosphorylation

down-regulates activity

0.604

The C-terminal tail of PTEN is also the target of mutations in tumors. As mentioned, this region contains the main phosphorylation sites mapped to residues Ser362, Thr366, Ser370, Ser380, Thr382, Thr383, and Ser385, and the kinases involved are casein kinase 2 (CK2), GSK3_, LKB1, and MAST.84,97-101 The phosphorylation of the tail has been shown to enhance PTEN stability but at the same time decrease its phosphatase activity

SIGNOR-161118

P53805

Q14469

0

transcriptional regulation

down-regulates quantity by repression

0.2

Increased Calcineurin/NFAT activity by Notch signaling involves downregulation of Calcipressin, an endogenous Calcineurin inhibitor, through a HES-1-dependent mechanism .... Chromatin immunoprecipitation (ChIP) analysis of keratinocytes overexpressing HES-1 showed that this protein can bind to the HES binding sites present in both distal and proximal promoters

SIGNOR-252026

O00159

P49841

0

phosphorylation

up-regulates activity

0.2

Here, we report that at early G1 the glycogen synthase kinase 3\u03b2 phosphorylates and stabilizes Nuclear myosin 1c, allowing for Nuclear myosin 1c association with the chromatin.

SIGNOR-279184

Q96T60

P78527

0

phosphorylation

up-regulates

0.649

We demonstrate that pnkp is phosphorylated by the dna-dependent protein kinase (dna-pk) and ataxia-telangiectasia mutated (atm) in vitro. The major phosphorylation site for both kinases was serine 114, with serine 126 being a minor site. Purified pnkp protein with mutation of serines 114 and 126 had decreased dna kinase and dna phosphatase activities and reduced affinity for dna in vitro.

SIGNOR-176020

P10828

P28482

0

phosphorylation

down-regulates activity

0.412

We concluded that serine 142 of the tr dbd is the likely site of phosphorylation by t(4)-activated mapk and that the docking site on tr for activated mapk includes residues 128-133 (kgffrr), a basic amino acid-enriched motif novel for mapk substrates. Tr mutations in the proposed mapk docking domain and at residue 142 modulated t(4)-conditioned shedding of co-repressor and recruitment of co-activator proteins by the receptor, and they altered transcriptional activity of tr in a thyroid hormone response element-luciferase reporter assay.

SIGNOR-102216

Q13627

P01106

1

phosphorylation

down-regulates quantity

0.374

We also found that DYRK1A phosphorylated c-Myc on Ser62, priming phosphorylation on Thr58 by GSK3\u03b2 and subsequent degradation.|c-Myc expression is down-regulated by DYRK1A.

SIGNOR-279609

P08908

Q5T0F9

0

transcriptional regulation

down-regulates quantity by repression

0.335

Human Freud-2/CC2D1B: a novel repressor of postsynaptic serotonin-1A receptor expression|Human Freud-2 showed strong repressor activity at the human 5-HT1A or heterologous promoter in human HEK-293 5-HT1A-negative cells and neuronal SK-N-SH cells, a model of postsynaptic 5-HT1A receptor-positive cells.

SIGNOR-268298

Q6P4F7

P61586

1

gtpase-activating protein

down-regulates activity

0.549

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-260466

Q9NY65

Q5SQI0

0

acetylation

up-regulates quantity by stabilization

0.244

Alpha-Tubulin acetyltransferase (alphaTAT1) is the major α-tubulin lysine-40 (K40) acetyltransferase in mammals, nematodes, and protozoa, and its activity plays a conserved role in several microtubule-based processes.|The tubulin subunits of microtubules are acetylated, and lysine-40 (K40) of the alpha-tubulin subunit has been identified as an important conserved site of microtubule acetylation (6–8). This modification is considered a hallmark of stable, long-lived microtubules

SIGNOR-272250

Q16625

P05771

0

phosphorylation

up-regulates activity

0.455

Protein kinase C regulates the phosphorylation and cellular localization of occludin. Ser(338) of occludin was identified as an in vitro protein kinase C phosphorylation site using peptide mass fingerprint analysis and electrospray ionization tandem mass spectroscopy. Both the phosphorylation of occludin and its incorporation into tight junctions induced by calcium switch were markedly inhibited by the PKC inhibitor GF-109203X.

SIGNOR-249106

P10451

Q8IXL6

0

phosphorylation

down-regulates quantity

0.683

OPN phosphorylation by Fam20C decreased OPN secretion, and OPN neutralization reduced Fam20C-deficiency-induced osteoclast differentiation and bone metastasis.

SIGNOR-278936

Q8TDC3

Q15831

0

phosphorylation

up-regulates

0.485

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

SIGNOR-122413

P08151

Q6PHR2

0

phosphorylation

up-regulates activity

0.673

We show that ULK3 is able to phosphorylate three mammalian GLI proteins in vitro. | Our data suggest that serine/threonine kinase ULK3 is involved in the SHH pathway as a positive regulator of GLI proteins.

SIGNOR-260797

P63000

O14827

0

guanine nucleotide exchange factor

up-regulates activity

0.498

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-260574

Q69YH5

Q96GD4

0

phosphorylation

down-regulates activity

0.446

This result demonstrates that the three sites of Repo-Man (Ser-543, Ser-977, and Ser-981) are phosphorylated by Aurora B in early mitosis. We uncover that PP1γ is recruited to mitotic chromosomes by its regulatory subunit Repo-Man in the absence of Aurora B activity and that Aurora B regulates dissociation of PP1γ by phosphorylating and disrupting PP1γ-Repo-Man interactions on chromatin.

SIGNOR-274001

P49759

Q96I25

1

phosphorylation

up-regulates activity

0.317

In this work, we show that Cdc2-like kinase 1 (Clk1) phosphorylates SPF45 on eight serine residues.

SIGNOR-262710

Q15349

P28482

0

phosphorylation

up-regulates

0.717

Erk-activates the rsk family of serine/threonine kinases,rsk1, rsk2, and rsk3.

SIGNOR-161515

P50053

P60891

1

phosphorylation

up-regulates activity

0.348

Ketohexokinase-A (KHK-A; also known as fructokinase-A) phosphorylates PRPS1 T225 and activates PRPS1 by blocking the binding of ADP, AMP, and GDP, which is required for hepatocellular carcinoma development

SIGNOR-265735

P35354

P15172

1

null

up-regulates

0.264

Furthermore, COX-2 inhibition reduced MyoD expression in regenerating muscle, suggesting a role for COX-2 in modulating muscle differentiation, as well as growth

SIGNOR-256214

Q9NQU5

P15976

1

phosphorylation

up-regulates activity

0.2

In addition, PAK5 knockdown also markedly reduced the association of GATA1 with HDAC3/4.|PAK5 phosphorylates the transcription factor GATA1 mainly at Ser161 and Ser 187, phosphorylated GATA1 recruits more HDAC3/4 to the promoter of E-cadherin and consequently suppresses the transcription of E-cadherin gene and promotes the EMT of breast cancer cells.

SIGNOR-278415

P52564

P19525

0

phosphorylation

up-regulates activity

0.2

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

SIGNOR-279707

P08238

P12931

0

phosphorylation

up-regulates

0.587

C-src directly phosphorylates hsp90 on tyrosine 300 residue and that this event is essential for vegf-stimulated enos association to hsp90 and thus no release from endothelial cells.

SIGNOR-157781

Q9UNE7

Q06787

1

ubiquitination

down-regulates quantity by destabilization

0.387

The results showed that FMR1 was ubiquitinated by CHIP WT or CHIP K30A. Also, ubiquitinated FMR1 accumulated in the presence of MG132, indicating that CHIP ubiquitinates FMR1 for proteasomal degradation ( Fig. 3 B).

SIGNOR-278599

P01137

P08047

0

transcriptional regulation

up-regulates quantity by expression

0.296

MAPKs have cis-acting regulatory elements in the mouse-TGF promoter region, which respond to various transcription factors, including specificity protein-1 and activating protein 1. Thus, it is possible that apoptotic cell-induced TGF-β mRNA expression is mediated through activation of these transcription factors via MAPK signaling. Xiao et al. reported that all of the MAPK members, including p38/ERK/JNK, are required for apoptotic Jurkat cells up-regulation of TGF-β production

SIGNOR-251740

Q13627

O75688

0

dephosphorylation

down-regulates activity

0.236

In conclusion, our study demonstrates that DYRK1A autophosphorylates Ser258, the dephosphorylation target of PPM1B, and PPM1B negatively regulates DYRK1A activity.|We found that PPM1B dephosphorylates DYRK1A at Ser258, contributing to the inhibition of DYRK1A activity.

SIGNOR-277108

P24941

Q12834

1

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

Q16236

Q92626

1

transcriptional regulation

up-regulates quantity by expression

0.2

PXDN expression in response to H2O2 and the Nrf2-specific inducers, tert-butylhydroquinone (tBHQ) and sulforaphane (SFN), was determined by western blotting and immunofluorescence microscopy, in HeLa and HEK293 cells.We found that Nrf2 binds to and increases luciferase reporter gene expression from the PXDN promoter via a putative Nrf2-binding site. In summary, we show that PXDN is a novel target of the redox sensitive transcription factor Nrf2.

SIGNOR-265248

Q3KR16

P53350

0

phosphorylation

up-regulates

0.415

We reported previously that a guanine nucleotide exchange factor, myogef, localizes to the central spindle, activates rhoa, and is required for cytokinesis. In this study, we have found that plk1 (polo-like kinase 1) can phosphorylate myogef, thereby recruiting myogef to the central spindle as well as enhancing myogef activity toward rhoa. The in vitro kinase assay shows that plk1 can phosphorylate myogef on threonine 574.

SIGNOR-179954

Q969R5

O76064

0

ubiquitination

up-regulates activity

0.242

L3MBTL2 links RNF8 and RNF168 in the DNA double strand break response. The protein kinase ATM phosphorylates L3MBTL2, which recruits it to the DNA lesion by promoting the interaction between MDC1 and L3MBTL2. L3MBTL2 is subsequently ubiquitinated by RNF8, which acts as a docking site for RNF168, thereby recruiting the ubiquitin ligase to the damage site. RNF168, in turn, ubiquitinates H2A-type histones to amplify the DNA damage response and recruit downstream DNA repair proteins for proper DSB signaling.

SIGNOR-266787

P69905

P09601

0

null

down-regulates activity

0.253

Heme oxygenase (HO), by catabolizing heme to bile pigments, down-regulates cellular hemoprotein, hemoglobin, and heme

SIGNOR-251813

Q9H9Z2

P01344

1

translation regulation

up-regulates quantity by expression

0.397

Lin-28 binds IGF-2 mRNA and participates in skeletal myogenesis by increasing translation efficiency

SIGNOR-277339

Q05397

P24844

1

phosphorylation

up-regulates activity

0.286

It indicates that FAK positively regulates the phosphorylation of MLC2.

SIGNOR-280098

P07948

Q9UK17

1

phosphorylation

up-regulates activity

0.2

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

SIGNOR-276395

Q8NHM5

Q99814

0

transcriptional regulation

up-regulates quantity by expression

0.2

To this end, we confirm that KDM3A, KDM4B, KDM4C, KDM5B, KDM5C, and KDM62 are direct targets of HIF-1a while extent the list of known targets to KDM2A, KDM2B, KDM4D, KDM5A, and KDM6A. The results demonstrated that majority of the KDMs were similarly induced (KDM2A, KDM2B, KDM3A, KDM4B, KDM4C, KDM4D, KDM5A, KDM5B, KDM5C, KDM6B, and KDM7A) or repressed (KDM NO66 and KDM1A) by both HIF-1a and HIF-2a.

SIGNOR-271582

P12830

Q15139

0

phosphorylation

up-regulates

0.451

Our study has identified e-cadherin as a novel substrate of pkd1, and phosphorylation of e-cadherin by pkd1 is associated with increased cellular aggregation and decreased cellular motility in prostate cancer.

SIGNOR-133856

P68363

Q8NG68

0

tyrosination

down-regulates

0.46

Tubulin tyrosine ligase (ttl) adds a c-terminal tyr to __tubulin as part of a tyrosination/detyrosination cycle present in most eukaryotic cells. / ttl inhibits spontaneous tubulin polymerization

SIGNOR-176915

Q969H0

P23769

1

ubiquitination

down-regulates quantity by destabilization

0.388

Here, we demonstrate that F-box/WD repeat-containing protein 7 (Fbw7/Fbxw7), a component of Skp1, Cullin 1, F-box-containing complex (SCF)-type E3 ligase, is an E3 ligase for GATA2. GATA2 contains a cell division control protein 4 (Cdc4) phosphodegron (CPD), a consensus motif for ubiquitylation by Fbw7, which includes Thr(176). Ectopic expression of Fbw7 destabilized GATA2 and promoted its proteasomal degradation.

SIGNOR-256005

O00418

P54646

0

phosphorylation

up-regulates activity

0.498

Stimulation of the AMP-activated Protein Kinase Leads to Activation of Eukaryotic Elongation Factor 2 Kinase and to Its Phosphorylation at a Novel Site, Serine 398. phosphorylation of eEF2 kinase at Ser-398 leads to an increase in its activity.

SIGNOR-250158

P10914

Q14164

0

phosphorylation

down-regulates activity

0.35

We demonstrated that IKK-ε phosphorylated the transcription factor IFN regulatory factor 1 (IRF-1) at amino acid (aa) 215/219/221 in primary CD4(+) T cells and blocked its transcriptional activity.

SIGNOR-276480

Q13315

Q5XUX0

1

phosphorylation

up-regulates

0.406

We find that dna damage induced by gamma-irradiation results in increased fbxo31 levels, which requires phosphorylation of fbxo31 by the ddr-initiating kinase atm

SIGNOR-185635

Q99961

P12931

0

phosphorylation

down-regulates

0.639

Further, we identified an interaction between fak's second pro-rich motif and endophilin a2's sh3 domain. This interaction served as an autophosphorylation-dependent scaffold to allow src phosphorylation of endophilin a2 at tyr315. Tyr315 phosphorylation inhibited endophilin/dynamin interactions, and blockade of tyr315 phosphorylation promoted endocytosis of mt1-mmp. Together, these results suggest a regulatory mechanism of cell invasion whereby fak promotes cell-surface presentation of mt1-mmp by inhibiting endophilin a2-dependent endocytosis.

SIGNOR-139150

P55072

Q16827

0

dephosphorylation

down-regulates activity

0.423

An important aspect of this study is that tyrosine dephosphorylation of VCP by PTPRO sensitizes HepG2 cells to Doxorubicin, a chemotherapeutic drug commonly used for a variety of cancers.

SIGNOR-277063

Q13200

Q92918

0

phosphorylation

up-regulates activity

0.2

Seven of these kinases (PIM1/2/3, MAP4K1/2, PKA, and NEK6) directly and robustly phosphorylated recombinant GST-Rpn1 at S361 in vitro (Fig. 3D and SI Appendix, Fig. S3 A and B).

SIGNOR-273899

Q99814

P28482

0

phosphorylation

up-regulates quantity by stabilization

0.25

The activation of ERK1/2 upon hypoxia promoted HIF-2alpha phosphorylation, enhancing its interaction with USP33.Here, we identified USP33 as essential deubiquitinase that stabilizes HIF-2alpha protein in an ERK1/2-dependent manner to promote hypoxia response in cancer cells.

SIGNOR-277585

Q99538

Q9Y4K3

0

polyubiquitination

up-regulates quantity by stabilization

0.307

We demonstrate that TRAF6 ubiquitinates the proform of AEP through K63-linked polyubiquitin, reversible by USP17, and forms a complex with HSP90α to subsequently promote pro-AEP intracellular stability as well as secretion. We now present evidence that AEP is a substrate for TRAF6 ubiquitination, resulting in AEP/TRAF6/HSP90α complex formation.

SIGNOR-272853

Q8NG27

P84022

1

ubiquitination

down-regulates activity

0.391

In summary, these results indicated that PJA1 promotes the ubiquitination of phosphorylated SMAD3, resulting in reduced activity of a TGF-\u03b2/SMAD3/\u03b22SP-dependent tumor-suppressing pathway in HCC cells ( xref ).

SIGNOR-278832

Q9H461

Q9ULT6

0

ubiquitination

down-regulates quantity

0.539

Here we show that the cell-surface transmembrane E3 ubiquitin ligase zinc and ring finger 3 (ZNRF3) and its homologue ring finger 43 (RNF43) are negative feedback regulators of Wnt signalling. ZNRF3 is associated with the Wnt receptor complex, and inhibits Wnt signalling by promoting the turnover of frizzled and LRP6.

SIGNOR-260111

P01019-PRO_0000420660

Q9BYF1

0

cleavage

up-regulates quantity

0.2

At first, ACE2 has been demonstrated to induce conversion of Ang I into Ang (1–7) by means of intermediate production of Ang (1–9), a fragment with unknown function.

SIGNOR-260227

Q04759

Q5JVS0

1

phosphorylation

down-regulates activity

0.303

We found a strong phosphorylation of Ki-1/57 by PKCalphabeta, PKCdelta, PKClambda/zeta, and especially by PKCsigma, however not by PKCmi. These data show that Ki-1/57 can serve in principal as a substrate for a wide variety of different PKC isoforms but also that its phosphorylation is strongest with PKCsigma. | This suggests that the two threonine residues present in this fragment (Thr354 and Thr375) might be the main target residues for phosphorylation by PKC in vitro. | Ki-1/57 Exits the Nucleus upon PMA Activation

SIGNOR-249256

Q76N32

Q96SN8

1

relocalization

up-regulates activity

0.452

We also found that Cep68 forms a complex with Cep215 (also known as Cdk5Rap2) and PCNT (also known as pericentrin), two PCM (pericentriolar material) proteins involved in centriole engagement. |Retention of Cep68 or PCNT in late mitosis prevents the removal of Cep215

SIGNOR-275624

P01100

P11511

1

transcriptional regulation

up-regulates quantity by expression

0.346

We found that both SF1 and LRH1 can transcriptionally cooperate with the AP-1 family members c-JUN and c-FOS, known to be associated with enhanced proliferation of endometrial carcinoma cells, to further enhance activation of the STAR, HSD3B2, and CYP19A1 PII promoters.

SIGNOR-254879

P38398

O75367

1

ubiquitination

up-regulates activity

0.2

BRCA1 Ubiquitinates K123 of mH2A1 in a Ligase-Activity-Dependent Manner.

SIGNOR-278752

P06493

Q16635

1

phosphorylation

down-regulates quantity by destabilization

0.266

Our studies suggest that phosphorylation and degradation of TAZ by Cdk1 may play important roles in apoptosis induced by antitubulin drugs.

SIGNOR-278240

P08100

Q15835

0

phosphorylation

up-regulates activity

0.923

That light-dependent phosphorylation of Rho is mediated primarily by RK. Addition of an inhibitory antibody against rhodopsin kinase (RK) lowered phosphorylation at Ser334, Ser338, and Ser343, without changing the ratio between phosphorylation sites. upon illumination, Ser334c, Ser338, and Ser343 are phosphorylated.

SIGNOR-251190

Q15424

P35637

1

relocalization

up-regulates activity

0.363

SAFB1 as well as Matrin3 to regulate splicing and ligand-mediated transcription| In addition, depletion of SAFB1 reduced FUS's localization to chromatin-bound fraction and splicing activity, suggesting SAFB1 could tether FUS to chromatin compartment thorough N-terminal DNA-binding motif.

SIGNOR-262821

Q13131

Q13554

0

phosphorylation

up-regulates

0.2

These data indicate that the camkks function in intact cells as ampkks, predicting wider roles for these kinases in regulating ampk activity in vivo.

SIGNOR-138360

Q96GD4

O14578

1

phosphorylation

down-regulates activity

0.283

Finally, Aurora B phosphorylates CIT-K to control its localization and interaction with central spindle partners.|Together these findings indicate that CIT-K is an Aurora B substrate and that Aurora B phosphorylation at S699 dampens the association of CIT-K with KIF23 and the chromosomal passenger complex in order to reduce CIT-K accumulation at the spindle midzone in early cytokinesis.

SIGNOR-279140

Q12926

O14672

1

post transcriptional regulation

up-regulates quantity

0.2

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

SIGNOR-266863

P17612

P19174

1

phosphorylation

down-regulates

0.2

The observation that pka also phosphorylates plc-yl on serine 1248 suggests that phosphorylation of this residue may be a common mechanism by which pkc and pka inhibit plc-yl.

SIGNOR-17901

Q13424

P53778

0

phosphorylation

up-regulates

0.668

Sapk3 phosphorylates alpha1-syntrophin at serine residues 193 and 201 in vitro and phosphorylation is dependent on binding to the pdz domain of alpha1-syntrophin. The finding that sapk3 co-localizes with _1-syntrophin in skeletal muscle, that it binds to the pdz domain of _1-syntrophin, and that phosphorylation of _1-syntrophin depends on this interaction identifies a novel mechanism for targeting a protein kinase to its substrates.

SIGNOR-67061

Q16236

Q9UPY5

1

transcriptional regulation

up-regulates quantity by expression

0.424

NFE2L2 is stabilized and translocates to the nucleus, where it dimerizes with sMAF proteins. This complex binds to AREs to mediate the transcription of genes involved in iron metabolism, GSH metabolism, and ROS detoxification. NFE2L2 directly binds to the promoter region of SLC7A11, leading to increased expression of this transporter, which in turn contributes to the resistance to ferroptosis and to radiotherapy

SIGNOR-279867

Q9UJV9

Q06187

0

phosphorylation

up-regulates activity

0.406

The kinase and SH3/SH2 interaction domains of BTK bind, respectively, the DEAD-box domain of DDX41 and transmembrane region of STING. BTK phosphorylates DDX41, and its kinase activities are critical for STING-mediated IFN-β production. We show that Tyr364 and Tyr414 of DDX41 are critical for its recognition of AT-rich DNA and binding to STING, and tandem mass spectrometry identifies Tyr414 as the BTK phosphorylation site.

SIGNOR-266404

Q12888

Q15759

0

phosphorylation

down-regulates activity

0.2

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

SIGNOR-264447

P49593

Q14012

1

dephosphorylation

down-regulates activity

0.461

Calmodulin-dependent protein kinase phosphatase (CaMKP) dephosphorylates and concomitantly deactivates multifunctional Ca(2+)/calmodulin-dependent protein kinases , such as CaMKI, CaMKII, and CaMKIV.

SIGNOR-277111

P78352

P35637

0

post transcriptional regulation

up-regulates quantity

0.27

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

SIGNOR-262103

P49841

Q05516

1

phosphorylation

up-regulates activity

0.2

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

SIGNOR-279618

Q16539

Q15717

1

phosphorylation

up-regulates

0.523

P38 mapk phosphorylates the mrna binding protein hur on thr118, which results in cytoplasmic accumulation of hur and its enhanced binding to the p21cip1 mrna.

SIGNOR-186135

Q15139

P61073

1

phosphorylation

down-regulates quantity

0.2

Inhibition of PKD activity restores membrane expression of CXCR4 and migration towards CXCL12 in BCR responsive cells in vitro.|This cascade consisted on a novel BCR dependent pathway in which PI3K-delta phosphorylates PKD, which in turn phosphorylates CXCR4 at Ser 324/325.

SIGNOR-279263

P28482

P33076

1

phosphorylation

up-regulates

0.432

We show in this study that the nuclear localized form of ciita is a predominantly phosphorylated form of the protein, whereas cytoplasmic ciita is predominantly unphosphorylated. Novel phosphorylation sites were determined to be located within a region that contains serine residues 286, 288, and 293. Double mutations of these residues increased nuclear ciita, indicating that these sites are not required for nuclear import. Erk1/2-mediated phosphorylation of ciita down-regulates ciita activity by priming it for nuclear export, thus providing a means for cells to tightly regulate the extent of antigen presentation.

SIGNOR-160609

O95999

Q96J02

0

ubiquitination

down-regulates quantity by destabilization

0.276

The HECT domain ubiquitin ligases NEDD4 and Itch promote ubiquitination and degradation of Bcl10, thus downmodulating NF-kappa B activation.

SIGNOR-271414

P84103

O15355

0

dephosphorylation

down-regulates activity

0.2

Here, we found that the PPM1G regulated SRSF3, and high levels of PPM1G decreased SRSF3 activity in HCC cells.|PPM1G interacted with SRSF3 and dephosphorylated SRSF3.

SIGNOR-277048

Q16584

P31749

0

phosphorylation

down-regulates

0.4

Negative regulation of mixed lineage kinase 3 by protein kinase b/akt leads to cell survivalthe expression of activated akt1 inhibits mlk3-mediated cell death in a manner dependent on serine 674 phosphorylation.

SIGNOR-252592

Q9H2D6

P53350

0

phosphorylation

up-regulates

0.335

Here we show that tara is a novel polo-like kinase 1 (plk1) target protein. Plk1 interacts with and phosphorylates tara in vivo and in vitro. Actually, the thr-457 in tara was a bona fide in vivo phosphorylation site for plk1. Interestingly, we found that the centrosomal localization of tara depended on the thr-457 phosphorylation and the kinase activity of plk1

SIGNOR-198353

P01111

Q07889

0

guanine nucleotide exchange factor

up-regulates activity

0.78

Sos and Ras-GRF are two families of guanine nucleotide exchange factors that activate Ras proteins in cells. Sos proteins are ubiquitously expressed and are activated in response to cell-surface tyrosine kinase stimulation Sos1 and Ras-GRF1 activate the Ras proteins Ha-Ras, N-Ras, and Ki-Ras

SIGNOR-110566

Q99816

Q6UWE0

0

monoubiquitination

down-regulates quantity

0.527

Tal increases ubiquitylation of Tsg101 and affects its solubility in a RING- and PTAP-dependent manner. Tal-mediated ubiquitylation of Tsg101 inactivates this sorting function and concomitantly translocates Tsg101 from relatively insoluble membrane subdomains. Presumably, the coordinated action of Tal and a deubiquitylation enzyme (DUB) enables recycling of Tsg101 and reloading of cargo.

SIGNOR-271509

Q13188

Q9H8S9

1

phosphorylation

up-regulates

0.85

Mob1, which forms a complex with lats1/2, is also phosphorylated by mst1/2, resulting in an enhanced lats1/2 mob1 interaction.

SIGNOR-175809

O15409

P78509

1

transcriptional regulation

up-regulates quantity by expression

0.365

By interacting with CASK, TBR1 regulates several ASD candidate genes, such as GRIN2B, AUTS2 and RELN—all of which are recurrently mutated in ASD. In areas of the brain with overlapping expression patterns, such as in glutamatergic layer 6 neurons, the TBR1–FOXP2 interaction may result in co-ordinated regulation of common downstream targets.

SIGNOR-266833

P60891

Q9NRM7

0

phosphorylation

down-regulates quantity by destabilization

0.2

Recruitment of TRAF2 to PRPS1/2 requires phosphorylation of PRPS1 S285 or PRPS2 T285, which is mediated by low stiffness-activated large tumor suppressor (LATS)1/2 kinases.LATS1/2-dependent S/T285 phosphorylation is required for PRPS1/2 ubiquitination and degradation at low stiffness.

SIGNOR-276504

Q9Y6K9

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-266743

P05129

P11388

1

phosphorylation

up-regulates activity

0.359

Here, we have shown that the enzymatic activity of topoisomerase II alpha protein purified from HeLa cell nuclei was strongly enhanced following phosphorylation by protein kinase C. | Site-directed mutagenesis studies indicated that phosphorylation of serine 29 generated both of these phosphopeptides.

SIGNOR-249196

P54646

Q96RR4

0

phosphorylation

up-regulates

0.619

These data indicate that the camkks function in intact cells as ampkks, predicting wider roles for these kinases in regulating ampk activity in vivo.

SIGNOR-138364

Q9BXL7

P31749

0

phosphorylation

up-regulates activity

0.522

Akt phosphorylates S637 and S645 in the linker region of Carma1

SIGNOR-276621

P40763

P28827

0

dephosphorylation

down-regulates activity

0.262

Thus PTPRM suppresses STAT3 signaling in DDIAS-knockdown cells, suggesting that DDIAS promotes the IL-6\u2013mediated STAT3 signaling in malignant cancer cells by inhibiting the PTPRM function.|We report that PTPRM is a novel STAT3 tyrosine phosphatase and that it negatively regulates STAT3 activation by dephosphorylating Y705 of STAT3 in the presence of IL-6.

SIGNOR-277016

Q12879

P12931

0

phosphorylation

up-regulates activity

0.567

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-247167

Q02577

Q96EB6

0

deacetylation

up-regulates activity

0.383

SIRT1 deacetylates the brain-specific helix-loop-helix transcription factor NHLH2 on lysine 49 to increase its activation of the MAO-A promoter

SIGNOR-254830

P56945

Q15678

0

dephosphorylation

down-regulates

0.394

We show that p130 crk-associated substrate (p130cas) is a direct substrate of ptpn14 and that ptpn14 specifically regulates p130cas phosphorylation at tyrosine residue 128 (y128) in colorectal cancer (crc) cells. We engineered crc cells homozygous for a p130cas y128f knock-in mutant and found that these cells exhibit significantly reduced migration and colony formation

SIGNOR-197923

O15524

P07948

0

phosphorylation

down-regulates activity

0.301

These findings show that SOCS1 phosphorylation by the SRC family inhibits its tumor-suppressive activity, indicating that patients with increased SOCS1 phosphorylation may benefit from SRC family kinase inhibitors.

SIGNOR-277888

Q9UNE7

Q01860

1

ubiquitination

down-regulates quantity by destabilization

0.303

CHIP overexpression decreased OCT4 stability through proteasomal degradation.|CHIP E3 ligase ubiquitinates OCT4 at lysine 284.|These data suggest that CHIP induces OCT4 ubiquitination and degradation.

SIGNOR-278562

P35558

P46379

0

acetylation

down-regulates quantity by destabilization

0.34

These results indicate that BAT3 and P300 can both exist in the PEPCK1 protein complex, suggesting the possibility that BAT3 could be an enhancer of PEPCK1 acetylation. | indicating a synergistic effect of BAT3 and P300 to promote PEPCK1 acetylation.

SIGNOR-267598

P29475

Q15139

0

phosphorylation

up-regulates activity

0.385

In addition, we demonstrate that protein kinase D1 activates nNOS by phosphorylating the activatory residue Ser1412, leading to increased \u00b7NO production, hence establishing a novel role of PKD in the regulation of \u00b7NO synthesis.|PKD1 phosphorylates nNOS at activatory Ser 1412 in vitro and in live cells.

SIGNOR-278426

P31995

P06241

0

phosphorylation

up-regulates activity

0.2

Fyn and Blk definitely phosphorylate Y-282 in the ITAM of FcgRIIa/c, whereas the non-ITAM tyrosine residue (Y-275) becomes phosphorylated by Syk, as the phosphorylation of double point mutants shows. In addition to these tyrosine residues, Fyn, Blk, and Syk might phosphorylate the most C-terminal tyrosine residue (Y-298) because altering this tyrosine residue together with one of the tyrosine residues clearly shown to be phosphorylated by the respective PTK results in the abrogation of phosphorylation

SIGNOR-262677

P78317

P08047

1

polyubiquitination

down-regulates quantity by destabilization

0.39

Here, we identified RNF4 as the ubiquitin E3 ligase of Sp1. From in vitro and in vivo experiments, we found that sumoylated Sp1 can recruit RNF4 as a ubiquitin E3 ligase that subjects sumoylated Sp1 to proteasomal degradation.

SIGNOR-272720

Q13490

Q9Y572

1

polyubiquitination

up-regulates activity

0.677

CIAP1/2 are direct E3 ligases conjugating diverse types of ubiquitin chains to receptor interacting proteins kinases 1 to 4 (RIP1-4).Together, our results demonstrate that depleting cIAP1/2 inhibits RIP1-4 mediated NF-kB activation without affecting RIP auto-phosphorylation.

SIGNOR-272711

Q00987

Q01130

0

transcriptional regulation

up-regulates quantity by expression

0.279

Using MDM2 P1 and P2 promoter-reporter systems, we screened clones regulating MDM2 transcriptions in a p53-independent manner by overexpression. Nine clones from the screening library showed enhanced MDM2 promoter activity and MDM2 expression in p53-deficient HCT116 cells. Among them, six clones, including NTRK2, GNA15, SFRS2, EIF5A, ELAVL1, and YWHAB mediated MAPK signaling for expressing MDM2.

SIGNOR-260076

Q9BY84

Q16539

1

dephosphorylation

down-regulates

0.805

Mkp-7 binds to and inactivates p38 mapk and jnk/sapk, but not erk inhibited by dual specificity phosphatases, such as dusp1, dusp10, and dusp16(uniprot)

SIGNOR-108233

P21675

P04637

1

phosphorylation

down-regulates

0.681

Phosphorylation on thr-55 by taf1 mediates degradation of p53

SIGNOR-123651

P31749

P15976

1

phosphorylation

up-regulates

0.514

We found that akt directly phosphorylates the transcription factor gata-1 at serine 310 and that this site-specific phosphorylation is required for the transcriptional activation of the timp-1 promoter.

SIGNOR-139782

Q9H2K2

O15169

1

ADP-ribosylation

down-regulates quantity by destabilization

0.705

Together, these findings are consistent with the hypothesis that TNKS promotes the ubiquitination and degradation of axin, which may be mediated, at least in part, through the direct PARsylation of axin.

SIGNOR-263378