GleghornLab/Signor_2class · Datasets at Hugging Face

IdA string	IdB string	labels int64	mechanism string	effect string	score float64	sentence string	signor_id string
Q06187	Q9UJV9	1	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
P30304	P49841	0	phosphorylation	down-regulates quantity by repression	0.313	Here, we report that casein kinase 1 alpha (ck1alpha) phosphorylates cdc25a on both s79 and s82 in a hierarchical manner requiring prior phosphorylation of s76 by chk1 or gsk-3beta. This facilitates beta-trcp binding and ubiquitin-mediated proteolysis of cdc25a	SIGNOR-164742
P06493	Q13415	1	phosphorylation	up-regulates	0.637	Horc1p contains three (s/t)px(k/r) consensus sites for cdk phosphorylation (ser258, ser273, and thr375). These data combined strongly suggest that skp2 promotes horc1p turnover and that the n-terminal domain of horc1p, containing most of the phosphorylation sites and overlapping with one of the skp2-interacting domains, is a regulatory element for horc1p stability.	SIGNOR-116329
Q9UQD0	Q13554	0	phosphorylation	up-regulates activity	0.272	CaMKII enhances voltage-gated sodium channel Nav1.6 activity and neuronal excitability\|mmobilized peptide arrays and nanoflow LC-electrospray ionization/MS of Nav1.6 reveal potential sites of CaMKII phosphorylation, specifically Ser-561 and Ser-641/Thr-642 within the first intracellular loop of the channel.	SIGNOR-275788
P12931	P35968	1	phosphorylation	up-regulates activity	0.614	In contrast, our analysis showed that over-expression of c-Src significantly enhances the ability of VEGFR-2 to stimulate proliferation of PAE cells and over-expression of dominant negative Src (Src kinase-dead) inhibits the VEGFR-2 driven proliferation of PAE cells (XREF_FIG).\|Taken together, the data demonstrate that Src kinases upon activation by VEGFR-2 phosphorylate Y1173 of VEGFR-2 (XREF_FIG).	SIGNOR-279120
P49585	Q02447	0	transcriptional regulation	up-regulates quantity by expression	0.2	Sp1 and Sp3 function as transcriptional activators of the Ctpct promoter	SIGNOR-266232
P06493	O94916	1	phosphorylation	up-regulates	0.2	High nacl-induced activation of cdk5 increases phosphorylation of the osmoprotective transcription factor tonebp/orebp at threonine 135, which contributes to its rapid nuclear localization. we performed in vitro kinase assays using the tonebp/orebp peptide containing t135 as substrate (figure 3b, right panel) and various recombinant kinases. The peptide is strongly phosphorylated by cdk5, less by cdk1.	SIGNOR-170882
Q9HD43	P00533	1	dephosphorylation	down-regulates activity	0.288	We further found that PTPRH and PTPRB directly dephosphorylate EGFR and repress its downstream signaling.	SIGNOR-277090
P40763	P42224	1	transcriptional regulation	up-regulates quantity by expression	0.615	In summary, we report in this study that STAT1 expression is upregulated by nuclear EGFR, EGFRvIII and HER2, and that STAT3 synergizes with the three receptors to further enhance STAT1 expression. These novel findings establish a novel link between the mitogenic ErbB signaling pathway and the inflammatory pathway mediated by STAT1. The oncogenic transcription factor STAT3 binds to the STAT1 promoter and synergizes with nuclear EGFR to significantly enhance STAT1 gene expression.	SIGNOR-263650
P22413	P0DMV9	0	post transcriptional regulation	up-regulates quantity	0.2	We demonstrated the binding of heat shock protein 70 (HSP70) to ENPP1-3'UTR. Through this binding, HSP70 stabilizes ENPP1 mRNA and increases ENPP1 transcript and protein levels. This positive modulation of ENPP1 expression is paralleled by a reduced insulin-induced IR and IRS-1 phosphorylation.	SIGNOR-252198
O60603	P03217	0	post transcriptional regulation	down-regulates quantity by repression	0.2	The RNA degradation induced by EBV BGLF5 can affect immunologically relevant proteins, including TLR2. Alkaline exonuclease involved in host shutoff, downregulates TLR2.	SIGNOR-266741
P41236	P68400	0	phosphorylation	up-regulates activity	0.307	Recombinant wild-type I-2 and the Ala-120/121 mutant were phosphorylated synergistically by GSK-3 and casein kinase II. The Thr-72 and Ser-86 mutants, however, did not undergo this synergistic phosphorylation. Our studies indicate that Thr-72 is the only GSK-3 site and that Ser-86 is the casein kinase II site required for the potentiation of GSK-3 action.	SIGNOR-250929
O75531	Q99986	0	phosphorylation	down-regulates	0.877	We demonstrate that phosphorylation of ser4 and/or thr2/thr3 abrogates the interaction of baf with dna and reduces its interaction with the lem domain. Coexpression of vrk1 and gfp-baf greatly diminishes the association of baf with the nuclear chromatin/matrix and leads to its dispersal throughout the cell	SIGNOR-144783
P00533	P35222	1	phosphorylation	up-regulates activity	0.773	EGFR and TRKA effect on WNT3a mediated Topflash induction was abolished by U0126 or expression of dominant negative LRP6-5A mutant (XREF_FIG), demonstrating that both EGFR and TRKA signal via ERK and LRP6 pathway to upregulate WNT and beta-catenin signaling.\|FGFR2, FGFR3, EGFR and TRKA Phosphorylate beta-catenin at Tyr142.	SIGNOR-278309
P31751	P46527	1	phosphorylation	down-regulates	0.53	Akt-induced t157 phosphorylation causes retention of p27(kip1) in the cytoplasm, precluding p27(kip1)-induced g1 arrest.[__]Thus, cytoplasmic relocalization of p27(kip1), secondary to akt-mediated phosphorylation, is a novel mechanism whereby the growth inhibitory properties of p27(kip1) are functionally inactivated and the proliferation of breast cancer cells is sustained.	SIGNOR-93122
Q9Y3M8	P61586	1	gtpase-activating protein	down-regulates activity	0.645	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-260521
P53350	Q12834	1	phosphorylation	down-regulates quantity by destabilization	0.977	Plk1 directly bound to Cdc20 and phosphorylates it on serine-170 located in CRY-box. Whereas wild-type Cdc20 was degraded according to progress cell cycle beyond mitosis, the phosphorylation-defective mutant, which serine-170 was changed into alanine, was not destroyed in early G1 phase.	SIGNOR-276493
Q99689	O95155	0	polyubiquitination	up-regulates activity	0.391	E4B mediated the polyubiquitylation of FEZ1 but did not affect its intracellular stability, suggesting that such modification of FEZ1 is not a signal for its proteolysis. Polyubiquitylation of FEZ1 by E4B required Lys(27) of ubiquitin. Expression of a dominant-negative mutant of E4B in rat pheochromocytoma PC12 cells resulted in inhibition of neurite extension induced either by nerve growth factor or by coexpression of FEZ1 and constitutively active PKCzeta. These findings indicate that E4B serves as a ubiquitin ligase for FEZ1 and thereby regulates its function but not its degradation. The polyubiquitin chain attached by E4B to FEZ1 might therefore facilitate the interaction of FEZ1 with an unidentified target that functions in neuritogenesis.	SIGNOR-271510
Q01892	P19784	0	phosphorylation	down-regulates quantity by destabilization	0.307	Phosphorylation of the Spi-B transcription factor reduces its intrinsic stability. \| Serine residues 37 in the transactivation domain and 129, 144 and 146 in the PEST domain of Spi-B are phosphorylated by CKII in vitro \| The CKII phosphorylation sites mapped in vitro are phosphorylated in vivo	SIGNOR-251042
Q9UPT9	Q96EB6	1	deubiquitination	up-regulates quantity by stabilization	0.534	USP22 expression was regulated by c-MYC and contributed to c-MYC mediated reduction in SIRT1 polyubiquitination and degradation. USP22 directly interacted with and removing polyubiquitin chains from SIRT1 to increase SIRT1 protein stabilization and expression. These results support a role for USP22 in MYC-mediated increase in SIRT1 protein stabilization, and indicate that FLT3-ITD, c-MYC and USP22 form an oncogenic network that enhances SIRT1 expression and activity in leukemic cells.	SIGNOR-261561
P00533	O14828	1	phosphorylation	up-regulates activity	0.399	In our efforts to identify cellular tyrosine kinases that phosphorylate SCAMPs, we are quite intrigued by the observation that among a number of kinases, only the EGFR exhibits activity toward SCAMPs. EGF catalyzes the progressive phosphorylation of the SCAMPs up to 1 h poststimulation and may enhance colocalization of the EGFR and SCAMP3 within the cell interior. EGF also induces SCAMP-EGFR association, as detected by coimmunoprecipitation, and phosphorylation of SCAMP3 is stimulated by the EGFR in vitro. These results suggest that phosphorylation of SCAMPs, either directly or indirectly, may be functionally linked to the internalization/down-regulation of the EGFR. we have observed that there are two tyrosines conserved in SCAMP1 and SCAMP3, which are not found in SCAMP2. Of these two tyrosines (Tyr37 and Tyr73 in SCAMP1; Tyr 41 and Tyr83 in SCAMP3), we consider Tyr37/41 to be a more likely site for tyrosine phosphorylation	SIGNOR-262858
P41143	P02775	0	chemical inhibition	down-regulates activity	0.385	Accordingly, for the OTDP, the binding affinity and activity of a large number of opiate compounds have been tested at μ-, δ-, and κ-opiate receptors. Binding studies were originally conducted in guinea pig brain membranes, and subsequent studies have been carried out in CHO cells transfected with human receptors. Table 7 shows a biochemical method for determining activity and potency of opioid compounds, stimulation of [35S]GTPγS binding in membranes from cells transfected with human μ, δ, or κ receptors.	SIGNOR-258412
P48735	Q9NTG7	0	deacetylation	up-regulates	0.657	Site-specific, genetic incorporation of n(_)-acetyllysine into position 413 of idh2 revealed that acetylated idh2 displays a dramatic 44-fold loss in activity. Deacetylation by sirt3 fully restored maximum idh2 activity.	SIGNOR-196617
P84022	P11802	0	phosphorylation	down-regulates activity	0.757	We have mapped CDK4 and CDK2 phosphorylation sites to Thr 8, Thr 178 and Ser 212 in Smad3. Mutation of the CDK phosphorylation sites increases Smad3 transcriptional activity	SIGNOR-232142
P49840	Q9NZQ7	1	phosphorylation	down-regulates quantity by destabilization	0.2	We find EGFR inhibitors promote PD-L1 ubiquitination and proteasomal degradation following GSK3α-mediated phosphorylation of Ser279/Ser283. We identify ARIH1 as the E3 ubiquitin ligase responsible for targeting PD-L1 to degradation.	SIGNOR-277552
Q8TF76	P06493	0	phosphorylation	up-regulates activity	0.2	Phosphorylation by Cyclin B-Cdk1 allows Haspin to bind Plk1-PBD. Phosphorylation of Haspin at T128 and Plk1 target sites is required for full H3T3ph generation and normal Aurora B localization in mitosis.	SIGNOR-275419
Q9Y4D8	Q8TEK3	0	transcriptional regulation	down-regulates quantity by repression	0.2	Overexpression of DOT1L decreased the expression of HECTD4 and MYCBP2 in LNCaP, C42B, and 22rv1 cells (Supplementary Fig. 5c), suggesting that DOT1L plays a role in repressing these targets either directly or indirectly.	SIGNOR-267150
P45984	Q13115	0	dephosphorylation	down-regulates	0.606	We assayed the relative ability of mkp-2, pac1, and mkp-1 to dephosphorylate erk2 and the other related map kinases, jnk2 and p38. . Mkp-2 had detectable activity against jnk2, although full inactivation of jnk2 was not observed even at the higher phosphatase concentration.	SIGNOR-40929
Q8IWU2	P13569	1	phosphorylation	down-regulates activity	0.401	The present study discovered that in human airway epithelial cells CFTR endocytosis is regulated by the LMTK2-mediated phosphorylation of CFTR-Ser737 that decreases the cell surface density of CFTR Cl\u2212 channels and inhibits CFTR-mediated Cl\u2212 secretion.\|Together, the above results demonstrate that the LMTK2 phosphorylation of CFTR-Ser737 facilitates CFTR endocytosis and reduces the plasma membrane abundance of CFTR in human airway epithelial cells.	SIGNOR-278227
Q13237	Q03393	1	phosphorylation	up-regulates	0.53	Upon expression in cos-1 cells, ptps-s19a was stable but not phosphorylated and had a reduced activity of approximately 33% in comparison to wild-type ptps. Addition of cgmp stimulated phosphotransferase activity 2-fold. Extracts from transfected cos-1 cells overexpressing cgkii stimulated ser(19) phosphorylation more than 100-fold.In assays with purified enzymes, wild-type but not ptps-s19a was a specific substrate for the cgmp-dependent protein kinase (cgk) type i and ii. Upon expression in cos-1 cells, ptps-s19a was stable but not phosphorylated and had a reduced activity of approximately 33% in comparison to wild-type ptps	SIGNOR-71751
P09874	Q13535	0	phosphorylation	down-regulates	0.357	Specifically, ATR binds to and phosphorylates PARP1 at Ser179 after the ionophore treatments.\|These data suggest that the phosphorylation of S179 is necessary and sufficient for ATR inhibition of PARP1 PARylation activity.	SIGNOR-278506
Q96MU7	P00519	0	phosphorylation	down-regulates	0.305	We show that yt521-b is tyrosine phosphorylated by c-abl in the nucleus.We propose that tyrosine phosphorylation causes sequestration of YT521-B in an insoluble nuclear form, which abolishes the ability of YT521-B to change alternative splice sites.	SIGNOR-125167
Q9Y3E7	Q9UN37	0	cleavage	up-regulates activity	0.625	Here, we show, using high-speed atomic force microscopy and electron microscopy, that the AAA-type adenosine triphosphatase VPS4 constricts and cleaves ESCRT-III CHMP2A-CHMP3 helical filaments in vitro. Our results demonstrate that VPS4 actively constricts ESCRT-III filaments and cleaves them before their complete disassembly. We propose that the formation of ESCRT-III dome-like end caps by VPS4 within a membrane neck structure constricts the membrane to set the stage for membrane fission.	SIGNOR-260847
P20807	P10636	1	cleavage	down-regulates activity	0.324	Besides tau phosphorylation, calpain activation might play a role in tau-mediated neurodegeneration by inducing tau cleavage. In vitro studies have shown that both fetal and adult tau isoforms are rapidly proteolyzed by calpains	SIGNOR-251605
P49841	P30279	1	phosphorylation	down-regulates	0.454	Glycogen synthase kinase-3beta and p38 phosphorylate cyclin d2 on thr280 to trigger its ubiquitin/proteasome-dependent degradation in hematopoietic cells	SIGNOR-154668
O95398	P61224	1	guanine nucleotide exchange factor	up-regulates activity	0.718	Epac1 (cAMP-GEFI) and Epac2 (cAMP-GEFII) are closely related guanine nucleotide exchange factors (GEFs) for the small GTPase Rap1, which are directly regulated by cAMP. Here we show that both GEFs efficiently activate Rap2 as well.	SIGNOR-263957
P04626	P12931	0	phosphorylation	up-regulates activity	0.615	In addition, the c-Src inhibitor 4-(4\u2019-phenoxyanilino)-6,7-dimethoxyquinazoline prevented SP-induced activation of HER2.\|On the other hand, c-Src directly phosphorylates the cytoplasmic tails of both EGFR and HER2, allowing the binding of scaffold proteins that will further activate signal transduction.	SIGNOR-279432
Q9UHD2	Q14653	1	phosphorylation	up-regulates activity	0.822	Virus-induced phosphoactivation of irf-3, thought to be mediated directly or indirectly by ikk? And/or tbk1 occurs in the c-terminal region of irf-3 at seven ser/thr residues, 385sslentvdlhisnshplslts405 (fig. 1a).Within This region, irf-3 has two phosphorylation sites: site 1 includes ser385 and ser386, whereas site 2 includes ser396, ser398, ser402, ser405, and thr404.	SIGNOR-178420
P68400	Q9Y237	1	phosphorylation	down-regulates activity	0.326	As proved by MALDI-TOF mass spectrometry and MS/MS fragmentation, hPar14 is phosphorylated at Ser19 in vitro and in vivo. In human HeLa cells the protein is most likely modified by casein kinase 2 (CK2). \|In contrast to wild-type hPar14, the in vitro DNA-binding affinity of the Glu19 mutant is strongly reduced, suggesting that only the dephosphorylated protein is the active DNA-binding form of hPar14 in the nucleus.	SIGNOR-265753
Q02817	Q99626	0	transcriptional regulation	up-regulates quantity by expression	0.2	COS-7 cells were transiently transfected with a CDX1 or CDX2 expression construct and then used for the luciferase assay, reverse transcription-polymerase chain reaction, and electrophoretic mobility shift assay (EMSA). The CDX2 expression construct activated the MUC2 promoter and increased the endogenous MUC2 mRNA level, while the CDX1 one did not.	SIGNOR-253966
Q12888	P60510	0	dephosphorylation	up-regulates activity	0.357	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 \|Depletion of PP4C, or PP4R3beta, causes persistence of phospho-T1609 and phospho-S1618	SIGNOR-264450
O95786	Q14258	0	ubiquitination	up-regulates activity	0.803	Lys63 linked polyubiquitination of RIG-I at Lys 172 catalyzed by TRIM25 is an important step for RIG-I activation.	SIGNOR-278730
P53350	Q9BVS4	1	phosphorylation	up-regulates activity	0.429	Here, we report that the atypical protein kinase Rio2 is a novel substrate of Plk1 and can be phosphorylated by Plk1 at Ser-335, Ser-380, and Ser-548. Overexpression of Rio2 causes a prolonged mitotic exit whereas knockdown of Rio2 accelerates mitotic progression, suggesting that Rio2 is required for the proper mitotic progression. F urthermore, time-lapse imaging data show that overexpression of Rio2 but not Rio2 S3A results in a slowed metaphase-anaphase transition. Collectively, these findings strongly indicate that the Plk1-mediated phosphorylation of Rio2 regulates metaphase-anaphase transition during mitotic progression.	SIGNOR-262937
P41743	P08670	1	phosphorylation	up-regulates activity	0.2	Results suggest that aPKCs target multiple activation sites (Ser33/39/56) on Vimentin and therefore is essential for VIF dynamics regulation during the metastasis of prostate cancer cells.	SIGNOR-277623
P17612	P08670	1	phosphorylation	down-regulates activity	0.309	Ser-46 was phosphorylated preferentially by cAMP-dependent protein kinase. Both kinases reacted with Ser-6, Ser-24, Ser-38, Ser-50, and Ser-65. Domain- and sequence-specific phosphorylation of vimentin induces disassembly of the filament structure.	SIGNOR-250068
P68400	P31749	1	phosphorylation	up-regulates	0.372	CK2 hyperactivates AKT by phosphorylation at Ser129	SIGNOR-252595
O14965	Q9NWT8	1	phosphorylation	up-regulates quantity by stabilization	0.681	AIP is phosphorylated on Serine 70 by Aurora‐A but not Aurora‐B and expression of phosphorylation mimic mutant of AIP results in prolonged protein stability compared to unphosphorylatable mutant. Phosphorylation of AIP Prolongs its Protein Stability	SIGNOR-262648
O15033	Q8N2W9	1	ubiquitination	down-regulates quantity by destabilization	0.403	In this study, we discovered a new protein isoform encoded by KIAA0317, termed fibrosis-inducing E3 ligase 1 (FIEL1), which potently stimulates the TGFβ signaling pathway through the site-specific ubiquitination of PIAS4.FIEL1 targets PIAS4 using a double locking mechanism that is facilitated by the kinases PKCζ and GSK3β. Specifically, PKCζ phosphorylation of PIAS4 and GSK3β phosphorylation of FIEL1 are both essential for the degradation of PIAS4.	SIGNOR-275575
Q15717	P49137	0	phosphorylation	up-regulates	0.303	Mk2 and mk3 participate in the control of gene expression mostly at the post-transcriptional level, by phosphorylating the are-binding proteins ttp and hur, and by regulating eef2k	SIGNOR-166622
P22681	P04626	1	ubiquitination	down-regulates quantity by destabilization	0.601	Ligand binding to EGFR also leads to rapid internalization and proteosomal/lysosomal degradation of the receptors. This process results in a dramatic downregulation of both total and cell surface receptors. EGF-induced degradation of EGFR is thought to be initiated by phosphorylation of tyrosine 1045 of the receptor followed by binding of Cbl adaptor proteins and ubiquitination of the receptor. Internalized EGFR is transported to early endosomes where receptor-ligand complexes are sorted for either degradation or recycling to the cell surface.	SIGNOR-30794
P53350	P14635	1	phosphorylation	up-regulates activity	0.922	Phosphorylation of cyclin b1 is central to its nuclear translocationduring cell-cycle progression in hela cells, a change in the kinase activity of endogenous plk1 toward s147 and/or s133 correlates with a kinase activity in the cell extractsa mutant cyclin b1 in which s133 and s147 are replaced by alanines remains in the cytoplasm, whereas wild-type cyclin b1 accumulates in the nucleus during prophase.Together, these results suggest that phosphorylation of s133 and s147 is necessary for the nuclear translocation of cyclin b1 during prophase, and that phosphorylation of s126 and s128 may stimulate the nuclear translocation.	SIGNOR-105719
O15226	P01574	1	transcriptional regulation	down-regulates quantity by repression	0.358	Constitutive silencing of IFN-beta promoter is mediated by NRF (NF-kappaB-repressing factor), a nuclear inhibitor of NF-kappaB	SIGNOR-266227
P02818	P38435	0	carboxylation	up-regulates activity	0.687	Thus, vitamin K acts as a cofactor for GGCX via the vitamin K cycle and exerts physiological effects through its regulation of VKDPs [29]. More than 20 VKDPs have been found. Osteocalcin promotes bone formation, and blood coagulation factors II, VII, IX, and X activate blood coagulation. Matrix Gla protein suppresses cardiovascular calcification, and brain-expressed Gas 6 promotes neural differentiation [29]. GGCX is an enzyme that converts glutamic acid (Glu) residues to Gla residues, so that the Gla-containing proteins can exert various physiological actions such as blood coagulation and bone formation.	SIGNOR-265922
P04637	P40692	1	transcriptional regulation	up-regulates quantity	0.61	.... numerous potentially novel targets, including the DNA mismatch repair genes MLH1 and PMS2. Both of these genes were determined to be responsive to DNA damage and p53 activation in normal human fibroblasts, and have p53-response elements within their first intron.	SIGNOR-257605
P24941	Q12974	0	dephosphorylation	up-regulates	0.2	Cells overexpressing prl-2 exhibited enhanced cyclin-dependent kinase 2 (cdk2) activity	SIGNOR-119478
Q12857	Q14938	1	transcriptional regulation	up-regulates quantity	0.2	We report that, in the absence of Nfia or Nfib, there is a marked reduction in the spinal cord expression of NFIX, and that NFIB can transcriptionally activate Nfix expression in vitro. These data demonstrate that NFIX is part of the downstream transcriptional program through which NFIA and NFIB coordinate gliogenesis within the spinal cord.	SIGNOR-268871
P05067	P55212	0	cleavage	up-regulates activity	0.724	Inhibition of caspase-6 activity prevents serum deprivation-mediated increase of Ab. Caspase-6 directly cleaves APP at the C terminus and generates a C-terminal fragment of 3 kDa (Capp3) and an Ab-containing 6.5-kDa fragment, Capp6.5, that increases in serum-deprived neurons	SIGNOR-261762
Q05469	P28482	0	phosphorylation	up-regulates activity	0.368	Thus, activation of the ERK pathway appears to be able to regulate adipocyte lipolysis by phosphorylating HSL on Ser(600) and increasing the activity of HSL.	SIGNOR-249413
Q9UHD2	Q13568	1	phosphorylation	up-regulates	0.541	Activation of interferon regulatory factor 5 by site specific phosphorylation. Although the gene induction by irf5 in the presence of tbk-1 was modest, phosphorylation by tbk-1 produced a significant shift in the mobility of irf5 in sds-page. For this reason we identified the residues that are phosphorylated on irf5 by tbk-1 with mass spectrometry. Ser-158 and ser-309 were found to be phosphorylated	SIGNOR-196528
Q9UEW8	O95863	1	phosphorylation	up-regulates activity	0.2	In this study, we found that STK39 also enhances SNAI1 stability by its phosphorylation at T203.\|STK39 interacts with SNAI1 and phosphorylates SNAI1 on T203.	SIGNOR-279128
P43115	P00533	1	relocalization	up-regulates quantity	0.332	These results demonstrate that PGE2 -mediated EGFR nuclear translocation requires the EP3 receptor.	SIGNOR-278884
P18031	Q9H1D0	1	dephosphorylation	down-regulates activity	0.631	In HEK293 cells, transfected with the Ca2+ channel protein TRPV6, Ca2+ influx is increased and TRPV6 is tyrosine phosphorylated following addition of the tyrosine phosphatase inhibitor\|PTP1B interacts with the N-terminal domain of TRPV6 within a region of amino acids 1-191 as shown by co-immunoprecipitation, bimolecular fluorescence complementation and the yeast 2-hybrid system. Point mutation of both tyrosines 161 and 162 in the TRPV6 protein abolishes the DMHV-effect on Ca2+ influx and tyrosine phosphorylation by Src. Single mutations of Y161 or Y162 shows that each of both tyrosines alone is sufficient for the DMHV-effect. We conclude that phosphorylation/dephosphorylation of tyrosines in position 161 and 162 is essential for regulation of Ca2+ influx through TRPV6 Ca2+ channels in HEK293 cells.	SIGNOR-248433
P12931	P25963	1	phosphorylation	down-regulates quantity by destabilization	0.688	C-src phosphorylates IkappaB On tyrosine 42\|NF-kappaB is sequestered in the cytosol by IkappaBalpha and, in most cells, released upon serine phosphorylation of this inhibitory protein which then undergoes rapid, ubiquitin-dependent degradation.	SIGNOR-60879
Q14012	P17600	1	phosphorylation	down-regulates activity	0.561	Synapsin phosphorylation in the A domain, at the only phosphorylation site shared by all synapsins, dissociates synapsins from synaptic vesicles.This site is located in the N-terminal A domain and is a substrate for both PKA and CaM Kinase I	SIGNOR-250615
Q02535	P24941	0	phosphorylation	down-regulates	0.342	We now show that an analogous cell-cycle-regulated phosphorylation of id3 alters the specificity of id3 for abrogating both e-box-dependent bhlh homo- or heterodimer complex formation in vitro and e-box-dependent reporter gene function in vivo._	SIGNOR-53306
P05787	O15264	0	phosphorylation	up-regulates	0.2	Keratin 8 (k8) serine 73 occurs within a relatively conserved type ii keratin motif . Here we show that ser-73 is exclusively phosphorylated in vitro by p38 mitogen-activated protein kinase. The ser-73 --> ala-associated filament reorganization defect is rescued by a ser-73 --> asp mutation. Also, disease-causing keratin mutations can modulate keratin phosphorylation and organization, which may affect disease pathogenesis.	SIGNOR-114075
P53778	P05787	1	phosphorylation	up-regulates	0.2	Keratin 8 (k8) serine 73 occurs within a relatively conserved type ii keratin motif . Here we show that ser-73 is exclusively phosphorylated in vitro by p38 mitogen-activated protein kinase. The ser-73 --> ala-associated filament reorganization defect is rescued by a ser-73 --> asp mutation. Also, disease-causing keratin mutations can modulate keratin phosphorylation and organization, which may affect disease pathogenesis.	SIGNOR-114067
P04637	P33981	0	phosphorylation	up-regulates	0.499	Ttk/hmps1 mediates the p53-dependent postmitotic checkpoint by phosphorylating p53 at thr18. phosphorylation at thr18 enhances p53-dependent activation of not only p21 but also lats2, two mediators of the postmitotic checkpoint.	SIGNOR-184931
P04626	O60674	0	phosphorylation	up-regulates activity	0.623	Our results indicate that autocrine secretion of PRL stimulates tyrosine phosphorylation of ErbB-2 by Jak2, provides docking sites for Grb2 and stimulates Ras-MAP kinase cascade, thereby causing unrestricted cellular proliferation.	SIGNOR-279197
P12830	Q00535	0	phosphorylation	down-regulates activity	0.298	Using both the Cdk inhibitor roscovitine and an RNA interference strategy, it was also demonstrated that Cdh1 was phosphorylated by Cdk5, an enzyme that can be persistently activated when bound to p25 [ xref ], the proteolytic product of p35 that has previously been shown to accumulate in the neurons of patients with Alzheimer\u2019s disease [ xref ].	SIGNOR-279679
Q14524	Q96PU5	0	ubiquitination	down-regulates quantity by destabilization	0.464	The control of Nav density at the cell membrane is crucial to ensuring normal neuronal excitability. Navs are subject to posttranslational modifications that may influence their cell membrane availability. Ubiquitylation is a key process that orchestrates the internalization and subsequent degradation or recycling of Navs. This is accomplished by ubiquitin protein ligases, such as NEDD4-2 (neuronal precursor cell expressed developmentally downregulated-4 type 2).	SIGNOR-253456
Q13315	Q92993	0	acetylation	up-regulates activity	0.8	Here, we report that sirtuin 7 (SIRT7)-mediated deacetylation is essential for dephosphorylation and deactivation of ATM. We show that SIRT7, a class III histone deacetylase, interacts with and deacetylates ATM in vitro and in vivo. \|Upon DNA damage, ATM is activated via a series of highly organized machineries, including acetylation by the histone acetyltransferase TIP60 at lysine 3016	SIGNOR-275891
P12931	P08238	1	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
Q15648	P28482	0	phosphorylation	up-regulates	0.354	We demonstrate that erk phosphorylates trap220/med1 in vivo at two specific sites: threonine 1032 and threonine 1457. importantly, we found that erk phosphorylation significantly increases the stability and half-life of trap220/med1 in vivo and correlates with increased thyroid hormone receptor-dependent transcription.	SIGNOR-142462
Q96J02	P06241	0	phosphorylation	down-regulates activity	0.366	Tyrosine phosphorylation of Itch appears to reduce its interaction with its substrate JunB. The turnover of JunB is accelerated in Fyn-deficient T cells, which is further reconstituted by Itch Tyr371 mutation	SIGNOR-245332
Q96P20	Q6PJ69	0	ubiquitination	down-regulates activity	0.2	These results suggest that TRIM65 could inhibit the activation of the NLRP3 inflammasome in response to multiple agonists.\|Thus, TRIM65 deficiency impairs NLRP3 ubiquitination and enhances NLRP3 inflammasome activation, but has no effects on AIM2 or IPAF inflammasome activation.	SIGNOR-278566
P63279	P06493	0	phosphorylation	up-regulates activity	0.512	Overall, these results suggest that Cdk1 and cyclin B mediates the phosphorylation of Ubc9 at serine 71.	SIGNOR-278174
Q13153	P30291	1	phosphorylation	down-regulates	0.299	Kinases targeted sequentially to the neck, cla4/pak and cdc5/polo, are responsible for stepwise phosphorylation and down-regulation of swe1.	SIGNOR-123528
Q08209	O00429	1	dephosphorylation	up-regulates activity	0.277	When mitochondrial depolarization is associated with sustained cytosolic Ca(2+) rise, it activates the cytosolic phosphatase calcineurin that normally interacts with Drp1. Calcineurin-dependent dephosphorylation of Drp1, and in particular of its conserved serine 637, regulates its translocation to mitochondria as substantiated by site directed mutagenesis.	SIGNOR-248676
P17252	O60500	1	phosphorylation	up-regulates activity	0.2	Binding of _-arrestin2 to the nephrin intracellular domain depended on phosphorylation of nephrin threonine residues 1120 and 1125 by pkc_.	SIGNOR-172056
P19838	P07288	1	transcriptional regulation	up-regulates quantity by expression	0.2	NF-kappa B activates prostate-specific antigen expression and is upregulated in androgen-independent prostate cancer.	SIGNOR-253668
Q96QS3	P17252	0	phosphorylation	up-regulates activity	0.2	We confirm that ARX is phosphorylated by PRKCA and demonstrate phosphorylation at serine 174. We demonstrate that phosphorylation is required for correct transcriptional activity of the ARX protein using transcriptome-wide analysis of gene expression of phospho-null mutants (alanines replacing serines) compared to ARX wild-type (ARX-WT) overexpressed in pancreatic alpha TC cells.	SIGNOR-277418
Q13131	P17600	1	phosphorylation	down-regulates activity	0.2	It has been reported that site 1 of syn i can be phosphorylated by pka. Pka-mediated synapsin i ser9 phosphorylation occurs in response to cgs 21680 treatment. Results show that the adenosine a2a receptor agonist, cgs 21680, increases neurotransmitter release, in particular, glutamate and noradrenaline and such response is mediated by protein kinase a activation, which in turn increased synapsin i phosphorylation	SIGNOR-78891
O14649	P17612	0	phosphorylation	up-regulates activity	0.2	Mutation of the ser393 to alanine, which can neither be phosphorylated nor mimic a phosphorylated residue, resulted in the channel failing to pass current all of our findings support the conclusion that camp-dependent protein kinase is responsible for the phosphorylation of the terminal serine in both k2p3.1 and k2p9.1.	SIGNOR-172430
Q96SN8	P05067	1	phosphorylation	up-regulates quantity by stabilization	0.2	The APPcyt is phosphorylated at Thr668 in vivo specifically in the brain. Cyclin‐dependent kinase 5 (Cdk5), a unique member of the Cdk family that is implicated in central nervous system development, participates in this phosphorylation. \| In the present study, we demonstrate that APP phosphorylated at Thr668 is less vulnerable to cytoplasmic cleavage by caspase-3 and caspase-8.	SIGNOR-260818
Q96RK0	P28482	0	phosphorylation	down-regulates	0.372	Specifically, 14-3-3 binds to p90(rsk)-phosphorylated ser?_??_ Of capic?_A thereby modulating dna binding to its hmg (high-mobility group) box, whereas erk phosphorylations prevent binding of a c-terminal nls (nuclear localization sequence) to importin ?4 (kpna3))[...] These results suggest that erk phosphorylation of ser1382 and ser1409 masks the nls and prevents its binding to kpna3	SIGNOR-169875
P0C0S5	Q86Y13	0	monoubiquitination	up-regulates activity	0.2	2A-HUB catalyzes monoubiquitination of H2A at lysine 119, functioning as a combinatoric component of the repression machinery required for specific gene regulation programs. Thus, 2A-HUB mediates a selective repression of a specific set of chemokine genes in macrophages, critically modulating migratory responses to TLR activation. H2A monoubiquitination acts to prevent FACT recruitment at the transcriptional promoter region, blocking RNA polymerase II release at the early stage of elongation.	SIGNOR-271748
Q15139	Q14247	1	phosphorylation	down-regulates	0.421	Pkd phosphorylates cortactin in vitro and in vivo at serine 298 thereby generating a 14-3-3 binding motif. In vitro, a phosphorylation-deficient cortactin-s298a protein accelerated vca-arp-cortactin-mediated synergistic actin polymerization and showed reduced f-actin binding	SIGNOR-164756
P49675	Q13285	0	transcriptional regulation	up-regulates quantity by expression	0.472	The in vivo existence of an SF-1 corepressor complex consisting of DAX-1, RNF31, and SMRT at the steroidogenic promoters of the human StAR and CYP19 genes. We demonstrate that RNF31 is necessary for the stable association of the DAX-1 corepressor complex with chromatin-bound SF-1, thereby inhibiting the recruitment of coactivators and Pol II and controlling basal transcription levels of SF-1 target genes.	SIGNOR-271788
P31749	P42574	0	cleavage	down-regulates activity	0.602	P53 can inhibit the survival function of integrins by inducing the caspase-dependent cleavage and inactivation of the serine/threonine kinase akt/pkb;the involvement of caspase 3 in akt/pkb regulation was indicated by the ability of z-devd-fmk, a caspase 3 inhibitor, to block the alpha6beta4-associated reduction in akt/pkb levels in vivo, and by the ability of recombinant caspase 3 to promote the cleavage of akt/pkb in vitro	SIGNOR-252624
P06493	Q99661	1	phosphorylation	down-regulates	0.686	We show here that cyclin-dependent kinase 1 (cdk1) phosphorylates t537 in the core domain of mcak and attenuates its microtubule-destabilizing activity in vitro and in vivo. Phosphorylation of mcak by cdk1 promotes the release of mcak from centrosomes and is required for proper spindle formation.	SIGNOR-164761
O15287	P06493	0	phosphorylation	up-regulates	0.355	S387a mutant abolished fancg fusion protein phosphorylation by cdc2.	SIGNOR-129061
Q8TDC3	P23258	1	phosphorylation	up-regulates	0.248	Sadb kinases associate and phosphorylate gamma-tubulin on ser 131 s131d gamma-tubulin expression amplifies centrosome duplication	SIGNOR-187405
Q92949	Q96DT5	1	transcriptional regulation	up-regulates quantity by expression	0.361	FOXJ1 expression in basal cells induced the expression of a panel of cilia-associated genes, including centrin 2 (CETN2); dynein, axonemal, heavy chain 11 (DNAH11); dynein, axonemal, intermediate chain 1 (DNAI1); dynein, axonemal, light intermediate chain 1 (DNALI1); EF-hand domain, C-terminal, containing 1 (EFHC1); sperm associated antigen 6 (SPAG6); tektin 1 (TEKT1), TEKT2 and tubulin, alpha 1a (TUBA1A; Figure 3C and Additional file 2: Table S1).	SIGNOR-266931
P08243	Q02447	0	transcriptional regulation	up-regulates quantity by expression	0.2	Sp1 and Sp3 Activate Transcription Driven by the AS Promoter	SIGNOR-268020
Q9BZS1	P42229	0	null	up-regulates	0.48	We demonstrate that the signal transducer and activator of transcription 5 (STAT5)-signaling cytokines, IL-2, IL-15 and to a lesser extent IL-7, induce FOXP3 up-regulation in vitro in activated human Teff cell	SIGNOR-254301
P09874	P17612	0	phosphorylation	up-regulates activity	0.2	In the presence of cAMP, recombinant PKA directly phosphorylated recombinant PARP1 on serines 465 (in the automodification domain) and 782 and 785 (both in the catalytic domain).	SIGNOR-276652
Q99075	P08254	0	cleavage	up-regulates	0.517	It was concluded that mmp-3 cleaves hb-egf at a specific site in the jm domain and that this enzyme might regulate the conversion of hb-egf from being a juxtacrine to a paracrine/autocrine growth factor.	SIGNOR-83339
Q5VWQ8	P31749	0	phosphorylation	down-regulates activity	0.497	DAB2IP can be phosphorylated by RIP1 on Ser 604 within the PER domain, and by AKT1 on Ser 847 within the proline-rich domain. Although RIP1-mediated phosphorylation is stimulatory,40 a recent study reported that AKT-mediated phosphorylation inhibits DAB2IP functions	SIGNOR-254780
Q9UNH5	Q16659	1	dephosphorylation	down-regulates	0.641	Using ms analysis, we identified four novel phosphorylation sites, ser684, ser688, thr698 and ser705, located at the extreme c-terminus of erk3.alanine substitution of the four c-terminal phosphorylation sites markedly decreased the half-life of erk3 in mitosis, thereby linking phosphorylation to the stabilization of the kinase.we found that the phosphatases cdc14a and cdc14b (cdc is cell-division cycle) bind to erk3 and reverse its c-terminal phosphorylation in mitosis.	SIGNOR-164412

Q06187

Q9UJV9

1

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

P30304

P49841

0

phosphorylation

down-regulates quantity by repression

0.313

Here, we report that casein kinase 1 alpha (ck1alpha) phosphorylates cdc25a on both s79 and s82 in a hierarchical manner requiring prior phosphorylation of s76 by chk1 or gsk-3beta. This facilitates beta-trcp binding and ubiquitin-mediated proteolysis of cdc25a

SIGNOR-164742

P06493

Q13415

1

phosphorylation

up-regulates

0.637

Horc1p contains three (s/t)px(k/r) consensus sites for cdk phosphorylation (ser258, ser273, and thr375). These data combined strongly suggest that skp2 promotes horc1p turnover and that the n-terminal domain of horc1p, containing most of the phosphorylation sites and overlapping with one of the skp2-interacting domains, is a regulatory element for horc1p stability.

SIGNOR-116329

Q9UQD0

Q13554

0

phosphorylation

up-regulates activity

0.272

CaMKII enhances voltage-gated sodium channel Nav1.6 activity and neuronal excitability|mmobilized peptide arrays and nanoflow LC-electrospray ionization/MS of Nav1.6 reveal potential sites of CaMKII phosphorylation, specifically Ser-561 and Ser-641/Thr-642 within the first intracellular loop of the channel.

SIGNOR-275788

P12931

P35968

1

phosphorylation

up-regulates activity

0.614

In contrast, our analysis showed that over-expression of c-Src significantly enhances the ability of VEGFR-2 to stimulate proliferation of PAE cells and over-expression of dominant negative Src (Src kinase-dead) inhibits the VEGFR-2 driven proliferation of PAE cells (XREF_FIG).|Taken together, the data demonstrate that Src kinases upon activation by VEGFR-2 phosphorylate Y1173 of VEGFR-2 (XREF_FIG).

SIGNOR-279120

P49585

Q02447

0

transcriptional regulation

up-regulates quantity by expression

0.2

Sp1 and Sp3 function as transcriptional activators of the Ctpct promoter

SIGNOR-266232

P06493

O94916

1

phosphorylation

up-regulates

0.2

High nacl-induced activation of cdk5 increases phosphorylation of the osmoprotective transcription factor tonebp/orebp at threonine 135, which contributes to its rapid nuclear localization. we performed in vitro kinase assays using the tonebp/orebp peptide containing t135 as substrate (figure 3b, right panel) and various recombinant kinases. The peptide is strongly phosphorylated by cdk5, less by cdk1.

SIGNOR-170882

Q9HD43

P00533

1

dephosphorylation

down-regulates activity

0.288

We further found that PTPRH and PTPRB directly dephosphorylate EGFR and repress its downstream signaling.

SIGNOR-277090

P40763

P42224

1

transcriptional regulation

up-regulates quantity by expression

0.615

In summary, we report in this study that STAT1 expression is upregulated by nuclear EGFR, EGFRvIII and HER2, and that STAT3 synergizes with the three receptors to further enhance STAT1 expression. These novel findings establish a novel link between the mitogenic ErbB signaling pathway and the inflammatory pathway mediated by STAT1. The oncogenic transcription factor STAT3 binds to the STAT1 promoter and synergizes with nuclear EGFR to significantly enhance STAT1 gene expression.

SIGNOR-263650

P22413

P0DMV9

0

post transcriptional regulation

up-regulates quantity

0.2

We demonstrated the binding of heat shock protein 70 (HSP70) to ENPP1-3'UTR. Through this binding, HSP70 stabilizes ENPP1 mRNA and increases ENPP1 transcript and protein levels. This positive modulation of ENPP1 expression is paralleled by a reduced insulin-induced IR and IRS-1 phosphorylation.

SIGNOR-252198

O60603

P03217

0

post transcriptional regulation

down-regulates quantity by repression

0.2

The RNA degradation induced by EBV BGLF5 can affect immunologically relevant proteins, including TLR2. Alkaline exonuclease involved in host shutoff, downregulates TLR2.

SIGNOR-266741

P41236

P68400

0

phosphorylation

up-regulates activity

0.307

Recombinant wild-type I-2 and the Ala-120/121 mutant were phosphorylated synergistically by GSK-3 and casein kinase II. The Thr-72 and Ser-86 mutants, however, did not undergo this synergistic phosphorylation. Our studies indicate that Thr-72 is the only GSK-3 site and that Ser-86 is the casein kinase II site required for the potentiation of GSK-3 action.

SIGNOR-250929

O75531

Q99986

0

phosphorylation

down-regulates

0.877

We demonstrate that phosphorylation of ser4 and/or thr2/thr3 abrogates the interaction of baf with dna and reduces its interaction with the lem domain. Coexpression of vrk1 and gfp-baf greatly diminishes the association of baf with the nuclear chromatin/matrix and leads to its dispersal throughout the cell

SIGNOR-144783

P00533

P35222

1

phosphorylation

up-regulates activity

0.773

EGFR and TRKA effect on WNT3a mediated Topflash induction was abolished by U0126 or expression of dominant negative LRP6-5A mutant (XREF_FIG), demonstrating that both EGFR and TRKA signal via ERK and LRP6 pathway to upregulate WNT and beta-catenin signaling.|FGFR2, FGFR3, EGFR and TRKA Phosphorylate beta-catenin at Tyr142.

SIGNOR-278309

P31751

P46527

1

phosphorylation

down-regulates

0.53

Akt-induced t157 phosphorylation causes retention of p27(kip1) in the cytoplasm, precluding p27(kip1)-induced g1 arrest.[__]Thus, cytoplasmic relocalization of p27(kip1), secondary to akt-mediated phosphorylation, is a novel mechanism whereby the growth inhibitory properties of p27(kip1) are functionally inactivated and the proliferation of breast cancer cells is sustained.

SIGNOR-93122

Q9Y3M8

P61586

1

gtpase-activating protein

down-regulates activity

0.645

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-260521

P53350

Q12834

1

phosphorylation

down-regulates quantity by destabilization

0.977

Plk1 directly bound to Cdc20 and phosphorylates it on serine-170 located in CRY-box. Whereas wild-type Cdc20 was degraded according to progress cell cycle beyond mitosis, the phosphorylation-defective mutant, which serine-170 was changed into alanine, was not destroyed in early G1 phase.

SIGNOR-276493

Q99689

O95155

0

polyubiquitination

up-regulates activity

0.391

E4B mediated the polyubiquitylation of FEZ1 but did not affect its intracellular stability, suggesting that such modification of FEZ1 is not a signal for its proteolysis. Polyubiquitylation of FEZ1 by E4B required Lys(27) of ubiquitin. Expression of a dominant-negative mutant of E4B in rat pheochromocytoma PC12 cells resulted in inhibition of neurite extension induced either by nerve growth factor or by coexpression of FEZ1 and constitutively active PKCzeta. These findings indicate that E4B serves as a ubiquitin ligase for FEZ1 and thereby regulates its function but not its degradation. The polyubiquitin chain attached by E4B to FEZ1 might therefore facilitate the interaction of FEZ1 with an unidentified target that functions in neuritogenesis.

SIGNOR-271510

Q01892

P19784

0

phosphorylation

down-regulates quantity by destabilization

0.307

Phosphorylation of the Spi-B transcription factor reduces its intrinsic stability. | Serine residues 37 in the transactivation domain and 129, 144 and 146 in the PEST domain of Spi-B are phosphorylated by CKII in vitro | The CKII phosphorylation sites mapped in vitro are phosphorylated in vivo

SIGNOR-251042

Q9UPT9

Q96EB6

1

deubiquitination

up-regulates quantity by stabilization

0.534

USP22 expression was regulated by c-MYC and contributed to c-MYC mediated reduction in SIRT1 polyubiquitination and degradation. USP22 directly interacted with and removing polyubiquitin chains from SIRT1 to increase SIRT1 protein stabilization and expression. These results support a role for USP22 in MYC-mediated increase in SIRT1 protein stabilization, and indicate that FLT3-ITD, c-MYC and USP22 form an oncogenic network that enhances SIRT1 expression and activity in leukemic cells.

SIGNOR-261561

P00533

O14828

1

phosphorylation

up-regulates activity

0.399

In our efforts to identify cellular tyrosine kinases that phosphorylate SCAMPs, we are quite intrigued by the observation that among a number of kinases, only the EGFR exhibits activity toward SCAMPs. EGF catalyzes the progressive phosphorylation of the SCAMPs up to 1 h poststimulation and may enhance colocalization of the EGFR and SCAMP3 within the cell interior. EGF also induces SCAMP-EGFR association, as detected by coimmunoprecipitation, and phosphorylation of SCAMP3 is stimulated by the EGFR in vitro. These results suggest that phosphorylation of SCAMPs, either directly or indirectly, may be functionally linked to the internalization/down-regulation of the EGFR. we have observed that there are two tyrosines conserved in SCAMP1 and SCAMP3, which are not found in SCAMP2. Of these two tyrosines (Tyr37 and Tyr73 in SCAMP1; Tyr 41 and Tyr83 in SCAMP3), we consider Tyr37/41 to be a more likely site for tyrosine phosphorylation

SIGNOR-262858

P41143

P02775

0

chemical inhibition

down-regulates activity

0.385

Accordingly, for the OTDP, the binding affinity and activity of a large number of opiate compounds have been tested at μ-, δ-, and κ-opiate receptors. Binding studies were originally conducted in guinea pig brain membranes, and subsequent studies have been carried out in CHO cells transfected with human receptors. Table 7 shows a biochemical method for determining activity and potency of opioid compounds, stimulation of [35S]GTPγS binding in membranes from cells transfected with human μ, δ, or κ receptors.

SIGNOR-258412

P48735

Q9NTG7

0

deacetylation

up-regulates

0.657

Site-specific, genetic incorporation of n(_)-acetyllysine into position 413 of idh2 revealed that acetylated idh2 displays a dramatic 44-fold loss in activity. Deacetylation by sirt3 fully restored maximum idh2 activity.

SIGNOR-196617

P84022

P11802

0

phosphorylation

down-regulates activity

0.757

We have mapped CDK4 and CDK2 phosphorylation sites to Thr 8, Thr 178 and Ser 212 in Smad3. Mutation of the CDK phosphorylation sites increases Smad3 transcriptional activity

SIGNOR-232142

P49840

Q9NZQ7

1

phosphorylation

down-regulates quantity by destabilization

0.2

We find EGFR inhibitors promote PD-L1 ubiquitination and proteasomal degradation following GSK3α-mediated phosphorylation of Ser279/Ser283. We identify ARIH1 as the E3 ubiquitin ligase responsible for targeting PD-L1 to degradation.

SIGNOR-277552

Q8TF76

P06493

0

phosphorylation

up-regulates activity

0.2

Phosphorylation by Cyclin B-Cdk1 allows Haspin to bind Plk1-PBD. Phosphorylation of Haspin at T128 and Plk1 target sites is required for full H3T3ph generation and normal Aurora B localization in mitosis.

SIGNOR-275419

Q9Y4D8

Q8TEK3

0

transcriptional regulation

down-regulates quantity by repression

0.2

Overexpression of DOT1L decreased the expression of HECTD4 and MYCBP2 in LNCaP, C42B, and 22rv1 cells (Supplementary Fig. 5c), suggesting that DOT1L plays a role in repressing these targets either directly or indirectly.

SIGNOR-267150

P45984

Q13115

0

dephosphorylation

down-regulates

0.606

We assayed the relative ability of mkp-2, pac1, and mkp-1 to dephosphorylate erk2 and the other related map kinases, jnk2 and p38. . Mkp-2 had detectable activity against jnk2, although full inactivation of jnk2 was not observed even at the higher phosphatase concentration.

SIGNOR-40929

Q8IWU2

P13569

1

phosphorylation

down-regulates activity

0.401

The present study discovered that in human airway epithelial cells CFTR endocytosis is regulated by the LMTK2-mediated phosphorylation of CFTR-Ser737 that decreases the cell surface density of CFTR Cl\u2212 channels and inhibits CFTR-mediated Cl\u2212 secretion.|Together, the above results demonstrate that the LMTK2 phosphorylation of CFTR-Ser737 facilitates CFTR endocytosis and reduces the plasma membrane abundance of CFTR in human airway epithelial cells.

SIGNOR-278227

Q13237

Q03393

1

phosphorylation

up-regulates

0.53

Upon expression in cos-1 cells, ptps-s19a was stable but not phosphorylated and had a reduced activity of approximately 33% in comparison to wild-type ptps. Addition of cgmp stimulated phosphotransferase activity 2-fold. Extracts from transfected cos-1 cells overexpressing cgkii stimulated ser(19) phosphorylation more than 100-fold.In assays with purified enzymes, wild-type but not ptps-s19a was a specific substrate for the cgmp-dependent protein kinase (cgk) type i and ii. Upon expression in cos-1 cells, ptps-s19a was stable but not phosphorylated and had a reduced activity of approximately 33% in comparison to wild-type ptps

SIGNOR-71751

P09874

Q13535

0

phosphorylation

down-regulates

0.357

Specifically, ATR binds to and phosphorylates PARP1 at Ser179 after the ionophore treatments.|These data suggest that the phosphorylation of S179 is necessary and sufficient for ATR inhibition of PARP1 PARylation activity.

SIGNOR-278506

Q96MU7

P00519

0

phosphorylation

down-regulates

0.305

We show that yt521-b is tyrosine phosphorylated by c-abl in the nucleus.We propose that tyrosine phosphorylation causes sequestration of YT521-B in an insoluble nuclear form, which abolishes the ability of YT521-B to change alternative splice sites.

SIGNOR-125167

Q9Y3E7

Q9UN37

0

cleavage

up-regulates activity

0.625

Here, we show, using high-speed atomic force microscopy and electron microscopy, that the AAA-type adenosine triphosphatase VPS4 constricts and cleaves ESCRT-III CHMP2A-CHMP3 helical filaments in vitro. Our results demonstrate that VPS4 actively constricts ESCRT-III filaments and cleaves them before their complete disassembly. We propose that the formation of ESCRT-III dome-like end caps by VPS4 within a membrane neck structure constricts the membrane to set the stage for membrane fission.

SIGNOR-260847

P20807

P10636

1

cleavage

down-regulates activity

0.324

Besides tau phosphorylation, calpain activation might play a role in tau-mediated neurodegeneration by inducing tau cleavage. In vitro studies have shown that both fetal and adult tau isoforms are rapidly proteolyzed by calpains

SIGNOR-251605

P49841

P30279

1

phosphorylation

down-regulates

0.454

Glycogen synthase kinase-3beta and p38 phosphorylate cyclin d2 on thr280 to trigger its ubiquitin/proteasome-dependent degradation in hematopoietic cells

SIGNOR-154668

O95398

P61224

1

guanine nucleotide exchange factor

up-regulates activity

0.718

Epac1 (cAMP-GEFI) and Epac2 (cAMP-GEFII) are closely related guanine nucleotide exchange factors (GEFs) for the small GTPase Rap1, which are directly regulated by cAMP. Here we show that both GEFs efficiently activate Rap2 as well.

SIGNOR-263957

P04626

P12931

0

phosphorylation

up-regulates activity

0.615

In addition, the c-Src inhibitor 4-(4\u2019-phenoxyanilino)-6,7-dimethoxyquinazoline prevented SP-induced activation of HER2.|On the other hand, c-Src directly phosphorylates the cytoplasmic tails of both EGFR and HER2, allowing the binding of scaffold proteins that will further activate signal transduction.

SIGNOR-279432

Q9UHD2

Q14653

1

phosphorylation

up-regulates activity

0.822

Virus-induced phosphoactivation of irf-3, thought to be mediated directly or indirectly by ikk? And/or tbk1 occurs in the c-terminal region of irf-3 at seven ser/thr residues, 385sslentvdlhisnshplslts405 (fig. 1a).Within This region, irf-3 has two phosphorylation sites: site 1 includes ser385 and ser386, whereas site 2 includes ser396, ser398, ser402, ser405, and thr404.

SIGNOR-178420

P68400

Q9Y237

1

phosphorylation

down-regulates activity

0.326

As proved by MALDI-TOF mass spectrometry and MS/MS fragmentation, hPar14 is phosphorylated at Ser19 in vitro and in vivo. In human HeLa cells the protein is most likely modified by casein kinase 2 (CK2). |In contrast to wild-type hPar14, the in vitro DNA-binding affinity of the Glu19 mutant is strongly reduced, suggesting that only the dephosphorylated protein is the active DNA-binding form of hPar14 in the nucleus.

SIGNOR-265753

Q02817

Q99626

0

transcriptional regulation

up-regulates quantity by expression

0.2

COS-7 cells were transiently transfected with a CDX1 or CDX2 expression construct and then used for the luciferase assay, reverse transcription-polymerase chain reaction, and electrophoretic mobility shift assay (EMSA). The CDX2 expression construct activated the MUC2 promoter and increased the endogenous MUC2 mRNA level, while the CDX1 one did not.

SIGNOR-253966

Q12888

P60510

0

dephosphorylation

up-regulates activity

0.357

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 |Depletion of PP4C, or PP4R3beta, causes persistence of phospho-T1609 and phospho-S1618

SIGNOR-264450

O95786

Q14258

0

ubiquitination

up-regulates activity

0.803

Lys63 linked polyubiquitination of RIG-I at Lys 172 catalyzed by TRIM25 is an important step for RIG-I activation.

SIGNOR-278730

P53350

Q9BVS4

1

phosphorylation

up-regulates activity

0.429

Here, we report that the atypical protein kinase Rio2 is a novel substrate of Plk1 and can be phosphorylated by Plk1 at Ser-335, Ser-380, and Ser-548. Overexpression of Rio2 causes a prolonged mitotic exit whereas knockdown of Rio2 accelerates mitotic progression, suggesting that Rio2 is required for the proper mitotic progression. F urthermore, time-lapse imaging data show that overexpression of Rio2 but not Rio2 S3A results in a slowed metaphase-anaphase transition. Collectively, these findings strongly indicate that the Plk1-mediated phosphorylation of Rio2 regulates metaphase-anaphase transition during mitotic progression.

SIGNOR-262937

P41743

P08670

1

phosphorylation

up-regulates activity

0.2

Results suggest that aPKCs target multiple activation sites (Ser33/39/56) on Vimentin and therefore is essential for VIF dynamics regulation during the metastasis of prostate cancer cells.

SIGNOR-277623

P17612

P08670

1

phosphorylation

down-regulates activity

0.309

Ser-46 was phosphorylated preferentially by cAMP-dependent protein kinase. Both kinases reacted with Ser-6, Ser-24, Ser-38, Ser-50, and Ser-65. Domain- and sequence-specific phosphorylation of vimentin induces disassembly of the filament structure.

SIGNOR-250068

P68400

P31749

1

phosphorylation

up-regulates

0.372

CK2 hyperactivates AKT by phosphorylation at Ser129

SIGNOR-252595

O14965

Q9NWT8

1

phosphorylation

up-regulates quantity by stabilization

0.681

AIP is phosphorylated on Serine 70 by Aurora‐A but not Aurora‐B and expression of phosphorylation mimic mutant of AIP results in prolonged protein stability compared to unphosphorylatable mutant. Phosphorylation of AIP Prolongs its Protein Stability

SIGNOR-262648

O15033

Q8N2W9

1

ubiquitination

down-regulates quantity by destabilization

0.403

In this study, we discovered a new protein isoform encoded by KIAA0317, termed fibrosis-inducing E3 ligase 1 (FIEL1), which potently stimulates the TGFβ signaling pathway through the site-specific ubiquitination of PIAS4.FIEL1 targets PIAS4 using a double locking mechanism that is facilitated by the kinases PKCζ and GSK3β. Specifically, PKCζ phosphorylation of PIAS4 and GSK3β phosphorylation of FIEL1 are both essential for the degradation of PIAS4.

SIGNOR-275575

Q15717

P49137

0

phosphorylation

up-regulates

0.303

Mk2 and mk3 participate in the control of gene expression mostly at the post-transcriptional level, by phosphorylating the are-binding proteins ttp and hur, and by regulating eef2k

SIGNOR-166622

P22681

P04626

1

ubiquitination

down-regulates quantity by destabilization

0.601

Ligand binding to EGFR also leads to rapid internalization and proteosomal/lysosomal degradation of the receptors. This process results in a dramatic downregulation of both total and cell surface receptors. EGF-induced degradation of EGFR is thought to be initiated by phosphorylation of tyrosine 1045 of the receptor followed by binding of Cbl adaptor proteins and ubiquitination of the receptor. Internalized EGFR is transported to early endosomes where receptor-ligand complexes are sorted for either degradation or recycling to the cell surface.

SIGNOR-30794

P53350

P14635

1

phosphorylation

up-regulates activity

0.922

Phosphorylation of cyclin b1 is central to its nuclear translocationduring cell-cycle progression in hela cells, a change in the kinase activity of endogenous plk1 toward s147 and/or s133 correlates with a kinase activity in the cell extractsa mutant cyclin b1 in which s133 and s147 are replaced by alanines remains in the cytoplasm, whereas wild-type cyclin b1 accumulates in the nucleus during prophase.Together, these results suggest that phosphorylation of s133 and s147 is necessary for the nuclear translocation of cyclin b1 during prophase, and that phosphorylation of s126 and s128 may stimulate the nuclear translocation.

SIGNOR-105719

O15226

P01574

1

transcriptional regulation

down-regulates quantity by repression

0.358

Constitutive silencing of IFN-beta promoter is mediated by NRF (NF-kappaB-repressing factor), a nuclear inhibitor of NF-kappaB

SIGNOR-266227

P02818

P38435

0

carboxylation

up-regulates activity

0.687

Thus, vitamin K acts as a cofactor for GGCX via the vitamin K cycle and exerts physiological effects through its regulation of VKDPs [29]. More than 20 VKDPs have been found. Osteocalcin promotes bone formation, and blood coagulation factors II, VII, IX, and X activate blood coagulation. Matrix Gla protein suppresses cardiovascular calcification, and brain-expressed Gas 6 promotes neural differentiation [29]. GGCX is an enzyme that converts glutamic acid (Glu) residues to Gla residues, so that the Gla-containing proteins can exert various physiological actions such as blood coagulation and bone formation.

SIGNOR-265922

P04637

P40692

1

transcriptional regulation

up-regulates quantity

0.61

.... numerous potentially novel targets, including the DNA mismatch repair genes MLH1 and PMS2. Both of these genes were determined to be responsive to DNA damage and p53 activation in normal human fibroblasts, and have p53-response elements within their first intron.

SIGNOR-257605

P24941

Q12974

0

dephosphorylation

up-regulates

0.2

Cells overexpressing prl-2 exhibited enhanced cyclin-dependent kinase 2 (cdk2) activity

SIGNOR-119478

Q12857

Q14938

1

transcriptional regulation

up-regulates quantity

0.2

We report that, in the absence of Nfia or Nfib, there is a marked reduction in the spinal cord expression of NFIX, and that NFIB can transcriptionally activate Nfix expression in vitro. These data demonstrate that NFIX is part of the downstream transcriptional program through which NFIA and NFIB coordinate gliogenesis within the spinal cord.

SIGNOR-268871

P05067

P55212

0

cleavage

up-regulates activity

0.724

Inhibition of caspase-6 activity prevents serum deprivation-mediated increase of Ab. Caspase-6 directly cleaves APP at the C terminus and generates a C-terminal fragment of 3 kDa (Capp3) and an Ab-containing 6.5-kDa fragment, Capp6.5, that increases in serum-deprived neurons

SIGNOR-261762

Q05469

P28482

0

phosphorylation

up-regulates activity

0.368

Thus, activation of the ERK pathway appears to be able to regulate adipocyte lipolysis by phosphorylating HSL on Ser(600) and increasing the activity of HSL.

SIGNOR-249413

Q9UHD2

Q13568

1

phosphorylation

up-regulates

0.541

Activation of interferon regulatory factor 5 by site specific phosphorylation. Although the gene induction by irf5 in the presence of tbk-1 was modest, phosphorylation by tbk-1 produced a significant shift in the mobility of irf5 in sds-page. For this reason we identified the residues that are phosphorylated on irf5 by tbk-1 with mass spectrometry. Ser-158 and ser-309 were found to be phosphorylated

SIGNOR-196528

Q9UEW8

O95863

1

phosphorylation

up-regulates activity

0.2

In this study, we found that STK39 also enhances SNAI1 stability by its phosphorylation at T203.|STK39 interacts with SNAI1 and phosphorylates SNAI1 on T203.

SIGNOR-279128

P43115

P00533

1

relocalization

up-regulates quantity

0.332

These results demonstrate that PGE2 -mediated EGFR nuclear translocation requires the EP3 receptor.

SIGNOR-278884

P18031

Q9H1D0

1

dephosphorylation

down-regulates activity

0.631

In HEK293 cells, transfected with the Ca2+ channel protein TRPV6, Ca2+ influx is increased and TRPV6 is tyrosine phosphorylated following addition of the tyrosine phosphatase inhibitor|PTP1B interacts with the N-terminal domain of TRPV6 within a region of amino acids 1-191 as shown by co-immunoprecipitation, bimolecular fluorescence complementation and the yeast 2-hybrid system. Point mutation of both tyrosines 161 and 162 in the TRPV6 protein abolishes the DMHV-effect on Ca2+ influx and tyrosine phosphorylation by Src. Single mutations of Y161 or Y162 shows that each of both tyrosines alone is sufficient for the DMHV-effect. We conclude that phosphorylation/dephosphorylation of tyrosines in position 161 and 162 is essential for regulation of Ca2+ influx through TRPV6 Ca2+ channels in HEK293 cells.

SIGNOR-248433

P12931

P25963

1

phosphorylation

down-regulates quantity by destabilization

0.688

C-src phosphorylates IkappaB On tyrosine 42|NF-kappaB is sequestered in the cytosol by IkappaBalpha and, in most cells, released upon serine phosphorylation of this inhibitory protein which then undergoes rapid, ubiquitin-dependent degradation.

SIGNOR-60879

Q14012

P17600

1

phosphorylation

down-regulates activity

0.561

Synapsin phosphorylation in the A domain, at the only phosphorylation site shared by all synapsins, dissociates synapsins from synaptic vesicles.This site is located in the N-terminal A domain and is a substrate for both PKA and CaM Kinase I

SIGNOR-250615

Q02535

P24941

0

phosphorylation

down-regulates

0.342

We now show that an analogous cell-cycle-regulated phosphorylation of id3 alters the specificity of id3 for abrogating both e-box-dependent bhlh homo- or heterodimer complex formation in vitro and e-box-dependent reporter gene function in vivo._

SIGNOR-53306

P05787

O15264

0

phosphorylation

up-regulates

0.2

Keratin 8 (k8) serine 73 occurs within a relatively conserved type ii keratin motif . Here we show that ser-73 is exclusively phosphorylated in vitro by p38 mitogen-activated protein kinase. The ser-73 --> ala-associated filament reorganization defect is rescued by a ser-73 --> asp mutation. Also, disease-causing keratin mutations can modulate keratin phosphorylation and organization, which may affect disease pathogenesis.

SIGNOR-114075

P53778

P05787

1

phosphorylation

up-regulates

0.2

Keratin 8 (k8) serine 73 occurs within a relatively conserved type ii keratin motif . Here we show that ser-73 is exclusively phosphorylated in vitro by p38 mitogen-activated protein kinase. The ser-73 --> ala-associated filament reorganization defect is rescued by a ser-73 --> asp mutation. Also, disease-causing keratin mutations can modulate keratin phosphorylation and organization, which may affect disease pathogenesis.

SIGNOR-114067

P04637

P33981

0

phosphorylation

up-regulates

0.499

Ttk/hmps1 mediates the p53-dependent postmitotic checkpoint by phosphorylating p53 at thr18. phosphorylation at thr18 enhances p53-dependent activation of not only p21 but also lats2, two mediators of the postmitotic checkpoint.

SIGNOR-184931

P04626

O60674

0

phosphorylation

up-regulates activity

0.623

Our results indicate that autocrine secretion of PRL stimulates tyrosine phosphorylation of ErbB-2 by Jak2, provides docking sites for Grb2 and stimulates Ras-MAP kinase cascade, thereby causing unrestricted cellular proliferation.

SIGNOR-279197

P12830

Q00535

0

phosphorylation

down-regulates activity

0.298

Using both the Cdk inhibitor roscovitine and an RNA interference strategy, it was also demonstrated that Cdh1 was phosphorylated by Cdk5, an enzyme that can be persistently activated when bound to p25 [ xref ], the proteolytic product of p35 that has previously been shown to accumulate in the neurons of patients with Alzheimer\u2019s disease [ xref ].

SIGNOR-279679

Q14524

Q96PU5

0

ubiquitination

down-regulates quantity by destabilization

0.464

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

SIGNOR-253456

Q13315

Q92993

0

acetylation

up-regulates activity

0.8

Here, we report that sirtuin 7 (SIRT7)-mediated deacetylation is essential for dephosphorylation and deactivation of ATM. We show that SIRT7, a class III histone deacetylase, interacts with and deacetylates ATM in vitro and in vivo. |Upon DNA damage, ATM is activated via a series of highly organized machineries, including acetylation by the histone acetyltransferase TIP60 at lysine 3016

SIGNOR-275891

P12931

P08238

1

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

Q15648

P28482

0

phosphorylation

up-regulates

0.354

We demonstrate that erk phosphorylates trap220/med1 in vivo at two specific sites: threonine 1032 and threonine 1457. importantly, we found that erk phosphorylation significantly increases the stability and half-life of trap220/med1 in vivo and correlates with increased thyroid hormone receptor-dependent transcription.

SIGNOR-142462

Q96J02

P06241

0

phosphorylation

down-regulates activity

0.366

Tyrosine phosphorylation of Itch appears to reduce its interaction with its substrate JunB. The turnover of JunB is accelerated in Fyn-deficient T cells, which is further reconstituted by Itch Tyr371 mutation

SIGNOR-245332

Q96P20

Q6PJ69

0

ubiquitination

down-regulates activity

0.2

These results suggest that TRIM65 could inhibit the activation of the NLRP3 inflammasome in response to multiple agonists.|Thus, TRIM65 deficiency impairs NLRP3 ubiquitination and enhances NLRP3 inflammasome activation, but has no effects on AIM2 or IPAF inflammasome activation.

SIGNOR-278566

P63279

P06493

0

phosphorylation

up-regulates activity

0.512

Overall, these results suggest that Cdk1 and cyclin B mediates the phosphorylation of Ubc9 at serine 71.

SIGNOR-278174

Q13153

P30291

1

phosphorylation

down-regulates

0.299

Kinases targeted sequentially to the neck, cla4/pak and cdc5/polo, are responsible for stepwise phosphorylation and down-regulation of swe1.

SIGNOR-123528

Q08209

O00429

1

dephosphorylation

up-regulates activity

0.277

When mitochondrial depolarization is associated with sustained cytosolic Ca(2+) rise, it activates the cytosolic phosphatase calcineurin that normally interacts with Drp1. Calcineurin-dependent dephosphorylation of Drp1, and in particular of its conserved serine 637, regulates its translocation to mitochondria as substantiated by site directed mutagenesis.

SIGNOR-248676

P17252

O60500

1

phosphorylation

up-regulates activity

0.2

Binding of _-arrestin2 to the nephrin intracellular domain depended on phosphorylation of nephrin threonine residues 1120 and 1125 by pkc_.

SIGNOR-172056

P19838

P07288

1

transcriptional regulation

up-regulates quantity by expression

0.2

NF-kappa B activates prostate-specific antigen expression and is upregulated in androgen-independent prostate cancer.

SIGNOR-253668

Q96QS3

P17252

0

phosphorylation

up-regulates activity

0.2

We confirm that ARX is phosphorylated by PRKCA and demonstrate phosphorylation at serine 174. We demonstrate that phosphorylation is required for correct transcriptional activity of the ARX protein using transcriptome-wide analysis of gene expression of phospho-null mutants (alanines replacing serines) compared to ARX wild-type (ARX-WT) overexpressed in pancreatic alpha TC cells.

SIGNOR-277418

Q13131

P17600

1

phosphorylation

down-regulates activity

0.2

It has been reported that site 1 of syn i can be phosphorylated by pka. Pka-mediated synapsin i ser9 phosphorylation occurs in response to cgs 21680 treatment. Results show that the adenosine a2a receptor agonist, cgs 21680, increases neurotransmitter release, in particular, glutamate and noradrenaline and such response is mediated by protein kinase a activation, which in turn increased synapsin i phosphorylation

SIGNOR-78891

O14649

P17612

0

phosphorylation

up-regulates activity

0.2

Mutation of the ser393 to alanine, which can neither be phosphorylated nor mimic a phosphorylated residue, resulted in the channel failing to pass current all of our findings support the conclusion that camp-dependent protein kinase is responsible for the phosphorylation of the terminal serine in both k2p3.1 and k2p9.1.

SIGNOR-172430

Q96SN8

P05067

1

phosphorylation

up-regulates quantity by stabilization

0.2

The APPcyt is phosphorylated at Thr668 in vivo specifically in the brain. Cyclin‐dependent kinase 5 (Cdk5), a unique member of the Cdk family that is implicated in central nervous system development, participates in this phosphorylation. | In the present study, we demonstrate that APP phosphorylated at Thr668 is less vulnerable to cytoplasmic cleavage by caspase-3 and caspase-8.

SIGNOR-260818

Q96RK0

P28482

0

phosphorylation

down-regulates

0.372

Specifically, 14-3-3 binds to p90(rsk)-phosphorylated ser?_??_ Of capic?_A thereby modulating dna binding to its hmg (high-mobility group) box, whereas erk phosphorylations prevent binding of a c-terminal nls (nuclear localization sequence) to importin ?4 (kpna3))[...] These results suggest that erk phosphorylation of ser1382 and ser1409 masks the nls and prevents its binding to kpna3

SIGNOR-169875

P0C0S5

Q86Y13

0

monoubiquitination

up-regulates activity

0.2

2A-HUB catalyzes monoubiquitination of H2A at lysine 119, functioning as a combinatoric component of the repression machinery required for specific gene regulation programs. Thus, 2A-HUB mediates a selective repression of a specific set of chemokine genes in macrophages, critically modulating migratory responses to TLR activation. H2A monoubiquitination acts to prevent FACT recruitment at the transcriptional promoter region, blocking RNA polymerase II release at the early stage of elongation.

SIGNOR-271748

Q15139

Q14247

1

phosphorylation

down-regulates

0.421

Pkd phosphorylates cortactin in vitro and in vivo at serine 298 thereby generating a 14-3-3 binding motif. In vitro, a phosphorylation-deficient cortactin-s298a protein accelerated vca-arp-cortactin-mediated synergistic actin polymerization and showed reduced f-actin binding

SIGNOR-164756

P49675

Q13285

0

transcriptional regulation

up-regulates quantity by expression

0.472

The in vivo existence of an SF-1 corepressor complex consisting of DAX-1, RNF31, and SMRT at the steroidogenic promoters of the human StAR and CYP19 genes. We demonstrate that RNF31 is necessary for the stable association of the DAX-1 corepressor complex with chromatin-bound SF-1, thereby inhibiting the recruitment of coactivators and Pol II and controlling basal transcription levels of SF-1 target genes.

SIGNOR-271788

P31749

P42574

0

cleavage

down-regulates activity

0.602

P53 can inhibit the survival function of integrins by inducing the caspase-dependent cleavage and inactivation of the serine/threonine kinase akt/pkb;the involvement of caspase 3 in akt/pkb regulation was indicated by the ability of z-devd-fmk, a caspase 3 inhibitor, to block the alpha6beta4-associated reduction in akt/pkb levels in vivo, and by the ability of recombinant caspase 3 to promote the cleavage of akt/pkb in vitro

SIGNOR-252624

P06493

Q99661

1

phosphorylation

down-regulates

0.686

We show here that cyclin-dependent kinase 1 (cdk1) phosphorylates t537 in the core domain of mcak and attenuates its microtubule-destabilizing activity in vitro and in vivo. Phosphorylation of mcak by cdk1 promotes the release of mcak from centrosomes and is required for proper spindle formation.

SIGNOR-164761

O15287

P06493

0

phosphorylation

up-regulates

0.355

S387a mutant abolished fancg fusion protein phosphorylation by cdc2.

SIGNOR-129061

Q8TDC3

P23258

1

phosphorylation

up-regulates

0.248

Sadb kinases associate and phosphorylate gamma-tubulin on ser 131 s131d gamma-tubulin expression amplifies centrosome duplication

SIGNOR-187405

Q92949

Q96DT5

1

transcriptional regulation

up-regulates quantity by expression

0.361

FOXJ1 expression in basal cells induced the expression of a panel of cilia-associated genes, including centrin 2 (CETN2); dynein, axonemal, heavy chain 11 (DNAH11); dynein, axonemal, intermediate chain 1 (DNAI1); dynein, axonemal, light intermediate chain 1 (DNALI1); EF-hand domain, C-terminal, containing 1 (EFHC1); sperm associated antigen 6 (SPAG6); tektin 1 (TEKT1), TEKT2 and tubulin, alpha 1a (TUBA1A; Figure 3C and Additional file 2: Table S1).

SIGNOR-266931

P08243

Q02447

0

transcriptional regulation

up-regulates quantity by expression

0.2

Sp1 and Sp3 Activate Transcription Driven by the AS Promoter

SIGNOR-268020

Q9BZS1

P42229

0

null

up-regulates

0.48

We demonstrate that the signal transducer and activator of transcription 5 (STAT5)-signaling cytokines, IL-2, IL-15 and to a lesser extent IL-7, induce FOXP3 up-regulation in vitro in activated human Teff cell

SIGNOR-254301

P09874

P17612

0

phosphorylation

up-regulates activity

0.2

In the presence of cAMP, recombinant PKA directly phosphorylated recombinant PARP1 on serines 465 (in the automodification domain) and 782 and 785 (both in the catalytic domain).

SIGNOR-276652

Q99075

P08254

0

cleavage

up-regulates

0.517

It was concluded that mmp-3 cleaves hb-egf at a specific site in the jm domain and that this enzyme might regulate the conversion of hb-egf from being a juxtacrine to a paracrine/autocrine growth factor.

SIGNOR-83339

Q5VWQ8

P31749

0

phosphorylation

down-regulates activity

0.497

DAB2IP can be phosphorylated by RIP1 on Ser 604 within the PER domain, and by AKT1 on Ser 847 within the proline-rich domain. Although RIP1-mediated phosphorylation is stimulatory,40 a recent study reported that AKT-mediated phosphorylation inhibits DAB2IP functions

SIGNOR-254780

Q9UNH5

Q16659

1

dephosphorylation

down-regulates

0.641

Using ms analysis, we identified four novel phosphorylation sites, ser684, ser688, thr698 and ser705, located at the extreme c-terminus of erk3.alanine substitution of the four c-terminal phosphorylation sites markedly decreased the half-life of erk3 in mitosis, thereby linking phosphorylation to the stabilization of the kinase.we found that the phosphatases cdc14a and cdc14b (cdc is cell-division cycle) bind to erk3 and reverse its c-terminal phosphorylation in mitosis.

SIGNOR-164412