GleghornLab/Signor_processed · Datasets at Hugging Face

IdA stringlengths 6 21	IdB stringlengths 6 21	mechanism stringclasses 40 values	effect stringclasses 10 values	score float64 0.1 0.99 ⌀	sentence stringlengths 10 1.63k ⌀	signor_id stringlengths 12 14
P25490	P07948	phosphorylation	down-regulates activity	0.2	In the case of Lyn overexpression, single mutations at either tyrosine 8, 254, or 383 severely reduced Lyn-mediated YY1 phosphorylation, suggesting that these three sites may be targets of Lyn in vivo (Fig. 3, A and B).	SIGNOR-276930
Q9BS26	Q86YB8	binding	up-regulates quantity by stabilization	0.2	Here, we report the functional characterization of a novel UPR-induced ER resident protein (ERp44) that forms mixed disulfides with both hEROs, as well as with partially unfolded Ig subunits.	SIGNOR-261048
Q99808	Q05655	phosphorylation	up-regulates activity	0.2	Phosphorylation of hENT1 by PKC has effects on both the function and subcellular trafficking of hENT1	SIGNOR-260888
Q9BR01	P27361	phosphorylation	down-regulates	0.2	The phosphorylation of sult4a1 allows interaction with pin1, which then promotes degradation of the sulfotransferase.	SIGNOR-168248
P84243	Q09472	acetylation	down-regulates activity	0.2	These results highlight the substrate and site specificities of hats in cells, demonstrate the distinct roles of gcn5/pcaf- and cbp/p300-mediated histone acetylations in gene activation, and suggest an important role of cbp/p300-mediated h3k18/27ac in nr-dependent transcription.	SIGNOR-170266
P02533	P06850	transcriptional regulation	down-regulates quantity by repression	0.2	CRH stimulated the expression of cytokeratin 1 and involucrin, and inhibited cytokeratin 14 on both mRNA and protein levels.	SIGNOR-251899
Q9Y4R8	P68400	phosphorylation	down-regulates	0.2	Here we report that tel2 and tti1 are targeted for degradation within mtorc1 by the scffbxo9 ubiquitin ligase to adjust mtor signalling to growth factor availability. This process is primed by ck2, which translocates to the cytoplasm to mediate mtorc1-specific phosphorylation of tel2/tti1. ere, we show that tel2 is constitutively phosphorylated on conserved serines 487 and 491 by casein kinase 2 (ck2)	SIGNOR-200202
O00257	Q9UNE7	ubiquitination	down-regulates quantity by destabilization	0.2	The phosphorylation of CBX4 at T437 by casein kinase 1α (CK1α) facilitated its ubiquitination at both K178 and K280 and subsequent degradation by CHIP, and this phosphorylation of CBX4 could be reduced by TNFα.	SIGNOR-277513
Q96PY5	P17252	phosphorylation	up-regulates activity	0.2	PKCα associates with and phosphorylates FMNL2 at S1072 within its Diaphanous autoregulatory region, leading to the release of formin autoinhibition.	SIGNOR-273796
P09471	Q9UNW8	binding	up-regulates activity	0.2	Here we systematically quantified ligand-induced interactions between 148 GPCRs and all 11 unique G alpha subunit C-termini. For each receptor, we probed chimeric G alpha subunit activation via a transforming growth factor-alpha (TGF alpha) shedding response in HEK293 cells lacking endogenous Gq/11- and G12/13- signaling. \| We defined positive coupling if any member of the subfamily scored LogRAi ≥ -1 and negative coupling if all of the members scored LogRAi < -1 (Figure 3A-B). ROC analysis gives AUC = 0.78 (Figure S4A) when considering high-confidence known coupling data and suggested a threshold of LogRAi ≥ -1.0 for defining true couplings. \| The score associated to this interaction has a LogRAi ≥ -1.0.	SIGNOR-257187
O43865	O15530	phosphorylation	down-regulates activity	0.2	Residue 68 resides in a consensus phosphorylation site for PKD (Figure 1A) [22,23]. Interestingly, phosphorylation of Ser68 could allow for subsequent phosphorylation of Ser71, Ser74, Ser77 and Ser80 by CK1, for which the consensus phosphorylation site is pS/T-X-X-S/T\| We found that phosphorylation of Ser71 and Ser74 were sufficient to enable inhibition of IP3 binding to the IP3R	SIGNOR-249174
Q9NRC8	P61289	binding	down-regulates quantity by destabilization	0.2	Here, the authors show that energy stress induces an AMPK-dependent phosphorylation of Sirt7, which promotes its ubiquitin-independent degradation by REGγ, resulting in the down-regulation of rRNA transcription and cell survival.\|These results strongly suggest that the phosphorylation status of SirT7 at T153 plays a crucial role in determining its subcellular distribution, degradation and binding to REGγ.	SIGNOR-275866
P35367	P17252	phosphorylation	down-regulates	0.2	In this study, we demonstrated that ser396 and ser398 are phosphorylated by pkc and, that phosphorylation of ser398 is particularly involved in pmainduced desensitization of the h1r.	SIGNOR-66015
P52630	Q7Z570	binding	up-regulates activity	0.2	Together these results indicate the formation of ZNF804A:STAT2 protein complex and its translocation from the cytoplasm into the nucleus upon IFN stimulation, suggesting that it may function as a signal transducer that activates IFN-mediated gene expression programs.	SIGNOR-269460
P21731-2	P35626	phosphorylation	down-regulates activity	0.2	These data suggest a model whereby agonist-induced PKC phosphorylation of Ser(145) partially impairs TPbeta signalling while GRK2/3 phosphorylation at both Ser(239) and Ser(357) within its IC(3) and C-tail domains, respectively, sterically inhibits G-protein coupling, profoundly desensitizing signalling, and promotes beta-arrestin association and, in turn, facilitates TPbeta internalization.	SIGNOR-274091
Q13148	O00311	phosphorylation	up-regulates activity	0.2	Among these, CDC7 directly phosphorylates TDP-43 on serines 409 and 410 both in vitro and in vivo .	SIGNOR-278256
P10636	Q9H992	ubiquitination	down-regulates activity	0.2	We have identified and characterized axotrophin, a protein that binds and preferentially mono-ubiquitinates tau protein.	SIGNOR-278655
Q9UN70	Q9Y5I2	binding	up-regulates activity	0.2	The clustered protocadherins comprise the largest subfamily of the cadherin superfamily and are predominantly expressed in the nervous system. Pcdh-alpha proteins interact with beta1-integrin to promote cell adhesion. They also form oligomers with Pcdh-gamma proteins at the same membrane sites.	SIGNOR-265696
Q13363	Q9BQ87	binding	down-regulates quantity by destabilization	0.2	TBL1 interacts in vivo with CtBP and promote its proteasomal degradation	SIGNOR-260902
Q03721	P05771	phosphorylation	down-regulates	0.2	We found that pkc specifically eliminates rapid inactivation of a cloned human a-type k+ channel (hkv3.4), converting this channel from a rapidly inactivating a type to a noninactivating delayed rectifier type.	SIGNOR-35626
Q9H808	Q96QT6	binding	up-regulates activity	0.2	We have cloned and characterized a new member of the PHD zinc finger family called Pf1 that interacts with two global transcription corepressors: mSin3A and TLE. Pf1 interacts with TLE. The Groucho/TLE proteins are members of an abundant corepressor family, and we hypothesized that Pf1 might interact with TLE family members. Together, these data suggest that in the absence of interactions with mSin3A, Gal4-Pf1 (102–273 L212P/A216P)-dependent repression can be attributed to interaction with endogenous TLE.	SIGNOR-266991
Q9Y2J4	P11362	phosphorylation	up-regulates activity	0.2	These data support an idea that Amotl2 Tyr-103 can be phosphorylated by FGF receptor tyrosine kinase activity. We then determined whether Amotl2 Tyr-103 is required for its interaction with c-Src. \|Amotl2 promotes MAPK/ERK activation via c-Src, which is dependent on phosphorylation of tyrosine residue at position 103 but independent of the C-terminal PDZ-binding domain.	SIGNOR-271869
P68431	Q9UGL1	demethylation	up-regulates activity	0.2	KDM5 subfamily is capable of removing tri‐ and di‐ methyl marks from lysine 4 on histone H3 (H3K4). Depending on the methylation site, its effect on transcription can be either activating or repressing.	SIGNOR-264302
Q03113	O14842	binding	up-regulates activity	0.2	Here we systematically quantified ligand-induced interactions between 148 GPCRs and all 11 unique G alpha subunit C-termini. For each receptor, we probed chimeric G alpha subunit activation via a transforming growth factor-alpha (TGF alpha) shedding response in HEK293 cells lacking endogenous Gq/11- and G12/13- signaling. \| We defined positive coupling if any member of the subfamily scored LogRAi ≥ -1 and negative coupling if all of the members scored LogRAi < -1 (Figure 3A-B). ROC analysis gives AUC = 0.78 (Figure S4A) when considering high-confidence known coupling data and suggested a threshold of LogRAi ≥ -1.0 for defining true couplings. \| The score associated to this interaction has a LogRAi ≥ -1.0.	SIGNOR-257338
Q53GL7	P53350	phosphorylation	up-regulates activity	0.2	PLK1, an important regulator for cell mitosis, directly interacts with and phosphorylates PARP10 at T601. PARP10 phosphorylation at T601 significantly decreases its binding to NEMO and disrupts its inhibition to NEMO ubiquitination, thereby enhancing the transcription activity of NF-κB toward multiple target genes and promoting HCC development.	SIGNOR-273728
O43791	P53671	phosphorylation	down-regulates activity	0.2	LIMK2 phosphorylates SPOP at S59, S171 and S226.\|Together, these results depict that LIMK2-mediated SPOP degradation is a key mechanism that regulates AR stability.	SIGNOR-278338
Q16695	P29375	demethylation	up-regulates activity	0.2	KDM5 subfamily is capable of removing tri‐ and di‐ methyl marks from lysine 4 on histone H3 (H3K4). Depending on the methylation site, its effect on transcription can be either activating or repressing.	SIGNOR-264300
P01100	P59595	transcriptional regulation	up-regulates quantity by expression	0.2	The transcription factors c-Fos, FosB, CREB-1, and ATF2 were all activated by the addition of SARS-CoV N protein to the sample well	SIGNOR-260726
Q13114	P0C6X7-PRO_0000037311	deubiquitination	down-regulates activity	0.2	Overexpressing PLPro of SARS-CoV or MERS-CoV significantly reduced the expression of IFN-Î² and proinflammatory cytokines in MDA5-stimulated 293T cells (83).Also, SARS-CoVPLPro catalyzed deubiquitination of TNF-receptor-associated factor3 (TRAF3) and TRAF6, thereby suppressing IFN-I and proinflammatory cytokines induced by TLR7 agonist (63). The deubiquitinating activity of SARS-CoV PLPro also suppressed a constitutively active phosphomimetic IRF3, suggesting its involvement in the postactivation signaling of IRF3	SIGNOR-260246
P54764	O00712	transcriptional regulation	up-regulates quantity	0.2	For example, within the NFI targetome, we identified 6 collagen genes, 13 genes encoding potassium channel or glutamate receptor subunits and a range of factors related to axon guidance (e.g. Slit1, Robo1, Epha4, Epha5, Epha8)	SIGNOR-268901
O14654	Q9UNE7	polyubiquitination	down-regulates quantity by destabilization	0.2	IRS4 was phosphorylated at Ser859 by CK1γ2 in vitro and in vivo, which promoted the polyubiquitination and degradation of IRS4 through the ubiquitin/lysosome pathway by the carboxyl terminus of Hsc70-interacting protein(CHIP).	SIGNOR-277616
Q14511	P30530	phosphorylation	up-regulates activity	0.2	Mechanistically, AXL phosphorylates NEDD9, leading to its binding to CRKII which in turn associates with and orchestrates the phosphorylation of the pseudo-kinase PEAK1.\|These results reveal NEDD9 as a specific AXL substrate.We next validated whether AXL promotes canonical NEDD9 signaling.	SIGNOR-278905
P52945	P49841	phosphorylation	down-regulates quantity	0.2	We show that glucose levels modulate PDX1 protein phosphorylation at a novel C-terminal GSK3 consensus that maps to serines 268 and 272. A decrease in glucose levels triggers increased turnover of the PDX1 protein in a GSK3-dependent manner, such that PDX1 phosphomutants are refractory to the destabilizing effect of low glucose	SIGNOR-255566
O95471	Q13547	transcriptional regulation	down-regulates quantity by repression	0.2	ChIP assays revealed that SNAI1P is recruited on the CLDN7 gene promoter along with the co-repressor CtBP1 and the effector HDAC1.\|These data further suggest that HDAC1 is involved in the SNAI1P-mediated repression of the human CLDN7 gene promoter.	SIGNOR-254106
P25098	P17612	phosphorylation	up-regulates activity	0.2	PKA directly phosphorylates GRK2 on serine 685. This modification increases G subunit binding to GRK2 and thus enhances the ability of the kinase to translocate to the membrane and phosphorylate the receptor.	SIGNOR-250334
Q96C90	Q05655	phosphorylation	up-regulates activity	0.2	Recombinant tagged PHI-1 was phosphorylated by protein kinase C at two sites, one a Ser and one a Thr; phosphorylation enhanced inhibitory potency 50-fold.	SIGNOR-265739
O15067	P28482	phosphorylation	up-regulates	0.2	T619 in PFAS is required to mediate ERK2-dependent purine synthesis stimulation. We demonstrate that ERK2, but not ERK1, phosphorylates the purine synthesis enzyme PFAS (phosphoribosylformylglycinamidine synthase) at T619 in cells to stimulate de novo purine synthesis. The expression of nonphosphorylatable PFAS (T619A) decreases purine synthesis, RAS-dependent cancer cell-colony formation, and tumor growth. Thus, ERK2-mediated PFAS phosphorylation facilitates the increase in nucleic acid synthesis required for anabolic cell growth and proliferation.	SIGNOR-267306
Q9UHD2	Q04759	phosphorylation	up-regulates activity	0.2	TBKBP1 recruits TBK1 to protein kinase C-theta (PKCθ) through a scaffold protein, CARD10. This enables PKCθ to phosphorylate TBK1 at Ser 716, a crucial step for TBK1 activation	SIGNOR-272472
Q13526	P45984	phosphorylation	up-regulates quantity by stabilization	0.2	Mechanistically, the JNK kinases directly bind to and phosphorylate PIN1 at Ser115, and this phosphorylation prevents PIN1 mono-ubiquitination at Lys117 and its proteasomal degradation.	SIGNOR-277563
O00548	P51608	transcriptional regulation	down-regulates quantity by repression	0.2	As the first step to reveal how MeCP2 phosphorylation may regulate Notch signaling, we conducted chromatin immunoprecipitation (ChIP) experiment to determine whether the phosphor-mutant MeCP2 protein has altered promoter occupancy at the promoters of Dll1 and Notch1. We found increased binding of the phosphor-mutant protein at the promoters of both Dll1 and Notch1	SIGNOR-264674
P36888	Q14469	transcriptional regulation	down-regulates quantity by repression	0.2	We then found that Hes1 directly bound to the promoter region of the FMS-like tyrosine kinase 3 (FLT3) gene and downregulated the promoter activity.	SIGNOR-261563
Q9NR31	Q9NRC8	deacetylation	up-regulates activity	0.2	SIRT7 interacts with the helicase DDX21. Deacetylation by SIRT7 is required for DDX21 activity and R-loop unwinding	SIGNOR-260978
P42336	O95819	phosphorylation	down-regulates activity	0.2	MST1/2 and HGK inhibit catalytic activity of p110α through phosphorylation at T1061	SIGNOR-277921
Q9Y261	O15111	phosphorylation	down-regulates	0.2	Here, we show that ikk_, an important downstream kinase of tnf_, interacts with and phosphorylates foxa2 at s107/s111, thereby suppressing foxa2 transactivation activity and leading to decreased numb expression	SIGNOR-195316
Q13363	Q13131	phosphorylation	down-regulates	0.2	We found that an activated amp-activated protein kinase (ampk) phosphorylates ctbp1 on ser-158 upon metabolic stresses. Moreover, ampk-mediated phosphorylation of ctbp1 (s158) attenuates the repressive function of ctbp1	SIGNOR-200250
P25208	P78317	binding	up-regulates activity	0.2	Coactivator RNF4 is involved in the GCH gene expression. Through serial deletion and mutagenesis studies of the GCH promoter, we defined the RNF4-responsive element on GCH proximal promoter as a CCAAT box. RNF4 did not possess specific DNA binding activity toward this CCAAT box, which suggests that RNF4 may be a coactivator of the CCAAT boxbinding protein nuclear factor Y (NF-Y). RNF4 is a coactivator for nuclear factor Y on GTP cyclohydrolase I proximal promoter.	SIGNOR-252230
P63092	Q96P68	binding	up-regulates activity	0.2	Here we systematically quantified ligand-induced interactions between 148 GPCRs and all 11 unique G alpha subunit C-termini. For each receptor, we probed chimeric G alpha subunit activation via a transforming growth factor-alpha (TGF alpha) shedding response in HEK293 cells lacking endogenous Gq/11- and G12/13- signaling. \| We defined positive coupling if any member of the subfamily scored LogRAi ‚â• -1 and negative coupling if all of the members scored LogRAi < -1 (Figure 3A-B). ROC analysis gives AUC = 0.78 (Figure S4A) when considering high-confidence known coupling data and suggested a threshold of LogRAi ‚â• -1.0 for defining true couplings. \| The score associated to this interaction has a LogRAi ‚â• -1.0.	SIGNOR-256770
P09471	Q99677	binding	up-regulates activity	0.2	Here we systematically quantified ligand-induced interactions between 148 GPCRs and all 11 unique G alpha subunit C-termini. For each receptor, we probed chimeric G alpha subunit activation via a transforming growth factor-alpha (TGF alpha) shedding response in HEK293 cells lacking endogenous Gq/11- and G12/13- signaling. \| We defined positive coupling if any member of the subfamily scored LogRAi ≥ -1 and negative coupling if all of the members scored LogRAi < -1 (Figure 3A-B). ROC analysis gives AUC = 0.78 (Figure S4A) when considering high-confidence known coupling data and suggested a threshold of LogRAi ≥ -1.0 for defining true couplings. \| The score associated to this interaction has a LogRAi ≥ -1.0.	SIGNOR-257258
P02675	P45452	cleavage	down-regulates quantity by destabilization	0.2	Matrix metalloproteinases collagenase-2, macrophage elastase, collagenase-3, and membrane type 1-matrix metalloproteinase impair clotting by degradation of fibrinogen and factor XII\| We have now investigated the role of collagenase-2 (MMP-8), macrophage elastase (MMP-12), collagenase-3 (MMP-13), and membrane type 1-matrix metalloproteinase (MT1-MMP, MMP-14) in the degradation of fibrinogen and Factor XII of the plasma clotting system.\|MMP-13 27YVATRDN g-chain\| 20ADSGEGD a-chain\| 124RNSVDXLNXN b-chain\| 442LRTGKEKV a-chain	SIGNOR-263615
P0DPK2	Q92831	acetylation	down-regulates activity	0.2	The HAT module within the SAGA and ADA complexes acetylates histone H3, mainly on residues K9 and K14.	SIGNOR-269614
Q92820	P08047	transcriptional regulation	up-regulates quantity by expression	0.2	Overexpression of Sp1 led to enhanced GGH promoter activity and GGH mRNA expression in allele-specific manners. These findings suggested that Sp1 acted as a positive regulator of human GGH transcription through the rs3758149 polymorphism in CEM/C1 cells.	SIGNOR-261350
Q96SR6	Q8NFU7	transcriptional regulation	up-regulates quantity by expression	0.2	Furthermore, TET1 catalytic domain possessed demethylase activity in cancer cells, being able to inhibit the CpG methylation of tumor suppressor gene (TSG) promoters and reactivate their expression, such as SLIT2, ZNF382 and HOXA9.	SIGNOR-259095
O14920	Q9Y5X2	binding	up-regulates activity	0.2	IFNγ induced JAK1-mediated phosphorylation of SNX8 at Tyr95 and Tyr126, which promoted the recruitment of IKKβ to the JAK1 complex.	SIGNOR-273646
P21730	Q05655	phosphorylation	down-regulates	0.2	Whole cell phosphorylation assays with specific inhibitors as well as in vitro phosphorylation assays with recombinant enzymes and peptide substrates revealed that phosphorylation of ser-334 is regulated by protein kinase c-beta this study is among the first to analyze in a detailed manner, using a non-mutational approach, modifications of a defined phosphorylation site in a g protein-coupled receptor and to correlate these findings with functional parameters of receptor deactivation.	SIGNOR-73967
Q13017	Q13882	phosphorylation	up-regulates	0.2	Breast tumor kinase phosphorylates p190rhogap to regulate rho and ras and promote breast carcinoma growth, migration, and invasion. Brk phosphorylates p190 at the y(1105) residue both in vitro and in vivo, thereby promoting the association of p190 with p120rasgap (p120). As a consequence, brk stimulates p190 and attenuates p120 functions, leading to rhoa inactivation and ras activation, respectively.	SIGNOR-181452
Q6PKG0	P24941	phosphorylation	up-regulates activity	0.2	CDK2 phosphorylates LARP1 protein, regulates TOP-protein expression and LARP1\u2019s translational activity.	SIGNOR-279015
Q16873	P23443	phosphorylation	down-regulates activity	0.2	Here, we identified Ser(36) as the major p70S6k phosphorylation site, along with a low frequency site at Thr(40), using an in vitro phosphorylation assay combined with mass spectrometry. Cellular LTC4S activity is suppressed by PKC-mediated phosphorylation, and recently a downstream p70S6k was shown to play an important role in this process.	SIGNOR-277256
Q06210	Q13131	phosphorylation	down-regulates	0.2	Amp-activated protein kinase phosphorylates glutamine : fructose-6-phosphate amidotransferase 1 at ser243 to modulate its enzymatic activityhe 2-dg induced phosphorylation of gfat1 . The assay of the gfat enzymatic activity in the cell lysates indicated that the 2-dg-treatment inhibited the enzymatic activity	SIGNOR-183528
P07288	Q02447	transcriptional regulation	up-regulates quantity by expression	0.2	We characterized four Sp1/Sp3 binding sites in the proximal promoter of the PSA gene. In a luciferase assay, these sites contributed to the basal promoter activity in prostate cancer cells. In an electrophoretic mobility shift assay and chromatin immunoprecipitation assay, we confirmed that Sp1 and Sp3 bind to these sites. Overexpression of wild-type Sp1 and Sp3 further upregulated the promoter activity, whereas overexpression of the Sp1 dominant-negative form or addition of mithramycin A significantly reduced the promoter activity and the endogenous mRNA level of PSA.	SIGNOR-253665
O95243	P17252	phosphorylation	up-regulates activity	0.2	Phosphorylation of MBD4 promotes 5-meC glycosylase activity Further evidence emerged to support the involvement of MBD4 in active demethylation. Protein-kinase C phosphorylation of MBD4 at two specific serine residues (165 and 262) following parathyroid hormone stimulation was shown to promote demethylation within the CYP27B1 gene promoter [12]	SIGNOR-275672
Q93008	O60729	dephosphorylation	down-regulates quantity by destabilization	0.2	Here, we find that CDC14B antagonizes CDK1-mediated activating mitotic phosphorylation of the deubiquitinase USP9X at serine residue 2563, which we show to be essential for USP9X to mediate mitotic survival. Starting from an unbiased proteome-wide screening approach, we specify Wilms' tumor protein 1 (WT1) as the relevant substrate that becomes deubiquitylated and stabilized by serine 2563-phosphorylated USP9X in mitosis.	SIGNOR-275613
Q02880	P48730	phosphorylation	down-regulates quantity by destabilization	0.2	Specifically, DNA damage signal, triggered by teniposide (VM-26) treatment, activates ATM, cooperating with CK1 to phosphorylate TOP2β on Ser1134 and Ser1130, respectively, in a canonical degron motif to facilitate β-TrCP binding and subsequent degradation.CK1 binds with and phosphorylates TOP2β at Ser1130 to promote its degradation by VM-26.	SIGNOR-277509
Q12913	P68400	phosphorylation	up-regulates activity	0.2	CK2-dependent phosphorylation of DEP-1 T1318 promotes Y1320 phosphorylation and Src activation upon VEGF stimulation.	SIGNOR-277876
Q8IX03	P51812	phosphorylation	up-regulates	0.2	Moreover, we found that rsk1/2 specifically phosphorylates kibra at two highly conserved sites (thr(929) and ser(947)) in vitro and in cells. Rsk-mediated phosphorylation is required for kibra binding to rsk1, but not rsk2.	SIGNOR-203302
Q71DI3	Q14493	translation regulation	up-regulates quantity by expression	0.2	Synthesis of mature histone mRNA requires only a single processing reaction: an endonucleolytic cleavage between a conserved stem-loop and a purine-rich downstream element to form the 3' end. The stem-loop binding protein (SLBP) is required for processing, and following processing, histone mRNA is transported to the cytoplasm, where SLBP participates in translation of the histone mRNA\|We used radiolabeled probes generated by PCR targeting the open reading frame (ORF) to detect histones H2A, H2B, H3, H4, and H1 and used 7SK snRNA as a loading control (Fig. 2A). The abundance of histone H2A, H2B, H3, and H4 mRNAs is reduced to 37% to 70% of control levels in the SLBP knockdown cells when compared to the C2 control.	SIGNOR-265414
P48730	Q5T0W9	binding	up-regulates quantity	0.2	We identified members of the FAM83 family of proteins as partners of CK1 in cells. All eight members of the FAM83 family (FAM83A–H) interacted with the α and α-like isoforms of CK1; FAM83A, -B, -E, and -H also interacted with the δ and ε isoforms of CK1. The intrinsic catalytic activity of CK1 is not affected by or required for the association of CK1 with FAM83 proteins. Our findings imply that the DUF1669 domains of FAM83 proteins anchor CK1 α, α-like, δ, and ε isoforms in specific subcellular compartments and potentially mediate their association with substrates.	SIGNOR-273766
P01574	P03209	transcriptional regulation	down-regulates quantity by repression	0.2	Epstein-Barr Virus BRLF1 Inhibits Transcription of IRF3 and IRF7 and Suppresses Induction of Interferon-β. These results suggest that EBV Rta is capable of regulating the activation of the IFN-β promoter.	SIGNOR-266646
Q8TE73	Q96M91	binding	up-regulates activity	0.2	CFAP53 likely facilitates the transport of TTC25 and the dyneins into cilia. CFAP53 at the centriolar satellites may form a complex with TTC25 and ODAs, including DNAH5 and DNAH11, and regulate their trafficking into the cilium (Fig 10B).	SIGNOR-265544
P35222	Q9H1B7	ubiquitination	down-regulates quantity by destabilization	0.2	FOXF2 directly bound the promoter of E3 ligase interferon regulatory factor 2-binding protein-like (IRF2BPL) and induced its transcriptional expression. IRF2BPL in turn interacted with β-catenin, increasing its ubiquitination and degradation.	SIGNOR-267153
P15036	Q9UQM7	phosphorylation	down-regulates	0.2	Camkii caused ets-2 phosphorylation.Serine 246, 310, and 313 were the targets. Camkii to phosphorylates ets-2, thus altering ets-2 binding to its downstream promoters	SIGNOR-183596
P62879	Q99835	binding	up-regulates	0.2	Consistent with its predicted topology, smo couples to a specific family of inhibitory g protein (gis) to regulate hh signaling.	SIGNOR-199177
P38117	Q8IXQ9	methylation	down-regulates activity	0.2	Accordingly, we found that METTL20-mediated methylation of ETFβ in vitro reduced its ability to receive electrons from the medium chain acyl-CoA dehydrogenase and the glutaryl-CoA dehydrogenase. In conclusion, the present study establishes METTL20 as the first human KMT localized to mitochondria and suggests that it may regulate cellular metabolism through modulating the interaction between its substrate ETFβ and dehydrogenases.	SIGNOR-269450
P43629	P05129	phosphorylation	down-regulates	0.2	Functional studies of the wild-type receptor and serine/threonine mutants indicated that phosphorylation of ser(394) by protein kinase c slightly suppresses kir3dl1 inhibitory function, and reduces receptor internalization and turnover.	SIGNOR-158133
Q13541	P49674	phosphorylation	down-regulates	0.2	Mechanistic investigations showed that ck1_ interacted with and phosphorylated 4e-bp1 at two novel sites t41 and t50, which were essential for 4e-bp1 inactivation along with increased mrna translation and cell proliferation.	SIGNOR-203240
P49959	P53350	phosphorylation	down-regulates activity	0.2	Plk1 phosphorylates Mre11 at S649.Mre11 phosphorylation at S649/S688 inhibits its binding to dsDNA and antagonizes the ATM signaling.	SIGNOR-265943
P35236	Q15139	phosphorylation	up-regulates activity	0.2	HePTP is phosphorylated by PKC isozymes at Ser-225 in vitro. While all isozymes phosphorylated Ser-225 predominantly and Ser-113 to a lesser extent (Fig. (Fig.5),5), they differed strikingly in how much 32P they incorporated into HePTP during the 30-min assay. PKC θ was the most efficient, while PKC ζ and PKC μ were clearly less potent; PKC δ, ɛ, and η were quite inefficient.	SIGNOR-276046
Q92952	P00533	phosphorylation	up-regulates activity	0.2	These results demonstrate the novel information that hSKCa1 channels are inhibited by genistein, T25 and AG556 via EGFR tyrosine kinase inhibition, which is related to the phosphorylation of Tyr(109) in the N-terminus.	SIGNOR-276490
P01189-PRO_0000024969	P16519	cleavage	up-regulates quantity	0.2	POMC is post-translationally cleaved by prohormone convertase enzymes 1 and 2 (PC1, PC2) into ACTH, an N-terminal glycopeptide	SIGNOR-268725
P68871	P15289	acetylation	up-regulates activity	0.2	ASA acetylates hemoglobin. Purified acetylated hemoglobin had a slightly increased oxygen affinity and decreased heme-heme interaction.	SIGNOR-251772
P05556	Q9UN74	binding	up-regulates activity	0.2	The clustered protocadherins comprise the largest subfamily of the cadherin superfamily and are predominantly expressed in the nervous system. Pcdh-alpha proteins interact with beta1-integrin to promote cell adhesion.	SIGNOR-265665
P68431	O15550	demethylation	down-regulates activity	0.2	Ubiquitously Transcribed Tetratricopeptide Repeat on chromosome X (UTX) and Jumonji D3 (JMJD3) as novel histone demethylases that catalyze the removal of di- and trimethyl groups on histone H3 lysine 27, thereby promoting target gene activation.	SIGNOR-260017
Q9C0B5	P04637	transcriptional regulation	up-regulates quantity by expression	0.2	Mechanistic investigations revealed that mutant p53 transcriptionally upregulated ZDHHC5 along with the nuclear transcription factor NF-Y	SIGNOR-261150
P23769	Q5D1E8	post transcriptional regulation	up-regulates quantity	0.2	Here, we show that Regnase-1 regulates self-renewal of HSPCs through modulating the stability of Gata2 and Tal1 mRNA	SIGNOR-259943
P32004	P17252	phosphorylation	down-regulates activity	0.2	CKII phosphorylates T1172 of the L1 CD and phosphorylation of T1172 is responsible for loss of 2C2 signal.	SIGNOR-276283
P19484	P11802	phosphorylation	up-regulates activity	0.2	CDK4 and CDK6 phosphorylate TFEB and TFE3.	SIGNOR-279450
Q8IW41	Q9UKI8	phosphorylation	up-regulates activity	0.2	We established that TLK1 phosphorylates MK5 on three residues (S160, S354 and S386), resulting in MK5 activation, and additionally, mobility shifts of MK5 also supported its phosphorylation by TLK1 in transfected HEK 293 cells.	SIGNOR-276747
Q9Y5G6	Q9Y5I2	binding	up-regulates activity	0.2	The clustered protocadherins comprise the largest subfamily of the cadherin superfamily and are predominantly expressed in the nervous system. Pcdh-alpha proteins interact with beta1-integrin to promote cell adhesion. They also form oligomers with Pcdh-gamma proteins at the same membrane sites.	SIGNOR-265709
P84243	P83916	binding	up-regulates activity	0.2	A core characteristic of heterochromatin is its association with heterochromatin protein 1 (HP1) proteins, a highly conserved family of chromosomal proteins that bind to di- and trimethylated H3K9 via a conserved N-terminal domain called the chromodomain (CD) HP1 proteins are a highly conserved family of eukaryotic proteins that bind to methylated histone H3 lysine 9 (H3K9) and are required for heterochromatic gene silencing.	SIGNOR-264491
Q6NXT2	Q14493	translation regulation	up-regulates quantity by expression	0.2	Synthesis of mature histone mRNA requires only a single processing reaction: an endonucleolytic cleavage between a conserved stem-loop and a purine-rich downstream element to form the 3' end. The stem-loop binding protein (SLBP) is required for processing, and following processing, histone mRNA is transported to the cytoplasm, where SLBP participates in translation of the histone mRNA\|We used radiolabeled probes generated by PCR targeting the open reading frame (ORF) to detect histones H2A, H2B, H3, H4, and H1 and used 7SK snRNA as a loading control (Fig. 2A). The abundance of histone H2A, H2B, H3, and H4 mRNAs is reduced to 37% to 70% of control levels in the SLBP knockdown cells when compared to the C2 control.	SIGNOR-265420
O43896	Q6ZP65	binding	up-regulates activity	0.2	BICDR-1 interacts with the dynein/dynactin motor complex. In young neurons, BICDR-1 accumulates Rab6 secretory vesicles around the centrosome, restricts anterograde secretory transport and inhibits neuritogenesis. Later during development, BICDR-1 expression is strongly reduced, which permits anterograde secretory transport required for neurite outgrowth. These results indicate an important role for BICDR-1 as temporal regulator of secretory trafficking during the early phase of neuronal differentiation. These results show that BICDR-1 regulates recruitment and/or activity of the anterograde kinesin motor Kif1C on Rab6 secretory carriers.	SIGNOR-266876
P84243	Q9UPS6	methylation	down-regulates activity	0.2	SETD1B encodes a lysine-specific methyltransferase that assists in transcriptional activation of genes by depositing H3K4 methyl marks.	SIGNOR-265578
Q9BXH1	Q92570	transcriptional regulation	up-regulates quantity by expression	0.2	Over-expression of NR4A3 attenuated proliferation of cancer cells and promoted apoptosis by augmenting the expression of pro-apoptotic genes, PUMA and Bax.	SIGNOR-259396
P48426	Q15139	phosphorylation	down-regulates	0.2	We conclude that the type ii pip kinases are physiological targets for pkd phosphorylation, and that this modification is likely to regulate inositol lipid turnover by inhibition of these lipid kinases.	SIGNOR-145370
Q5TEC6	Q9NRC8	deacetylation	up-regulates activity	0.2	Besides confirming the previously reported histone H3K18 deacylation activity, our results revealed that SIRT7 has an astonishingly high activity to catalyze deacylation of H3K36 and is also catalytically active to deacylate H3K37.	SIGNOR-275883
Q15109	Q13315	phosphorylation	up-regulates activity	0.2	RAGE is phosphorylated at Serine 376 and Serine 389 by the ATM kinase and is recruited to the site of DNA-DSBs via an early DNA damage response.	SIGNOR-278907
Q99250	Q8NEV1	phosphorylation	up-regulates activity	0.2	We found that the ankyrin-binding motif of Na(v)1.2 that determines channel concentration at the AIS depends on a glutamate residue (E1111), but also on several serine residues (S1112, S1124, and S1126). We showed that phosphorylation of these residues by protein kinase CK2 (CK2) regulates Na(v) channel interaction with ankyrins. \| inhibition of CK2 activity reduced sodium channel accumulation at the AIS of neurons. In conclusion, CK2 contributes to sodium channel organization by regulating their interaction with ankyrin G.	SIGNOR-275755
O95243	P63279	sumoylation	up-regulates activity	0.2	MBD4 is sumoylated at three main sites: K137, K215 and K377.\|Sumoylation increases the G:T repair activity of MBD4 in cell extracts.\|we conducted an in vitrosumoylation assay, employing recombinant activating E1 (Aos1-Uba2) and conjugating E2 (Ubc9) enzymes, along with recombinant YFP-SUMO1 and MBD4 or, as positive control for sumoylation, TDG (Fig. 2D). These results indicate that MBD4 is sumoylated in vivo and in vitro.	SIGNOR-275678
P04628	P11308	transcriptional regulation	up-regulates quantity by expression	0.2	Interestingly, our data showed that ERG drastically induced Wnt ligand gene expression.	SIGNOR-261597
P38405	P47900	binding	up-regulates activity	0.2	Here we systematically quantified ligand-induced interactions between 148 GPCRs and all 11 unique G alpha subunit C-termini. For each receptor, we probed chimeric G alpha subunit activation via a transforming growth factor-alpha (TGF alpha) shedding response in HEK293 cells lacking endogenous Gq/11- and G12/13- signaling. \| We defined positive coupling if any member of the subfamily scored LogRAi ≥ -1 and negative coupling if all of the members scored LogRAi < -1 (Figure 3A-B). ROC analysis gives AUC = 0.78 (Figure S4A) when considering high-confidence known coupling data and suggested a threshold of LogRAi ≥ -1.0 for defining true couplings. \| The score associated to this interaction has a LogRAi ≥ -1.0.	SIGNOR-256943
P30793	P04792	binding	up-regulates quantity by stabilization	0.2	GTP cyclohydrolase I (GCH), an oligomeric protein composed of 10 identical subunits, is required for the synthesis of neurotransmitters; mutations in GCH are associated with dopa-responsive dystonia (DRD) and hyperphenylalaninemia. Mutated GCH proteins are unstable and prone to dominant-negative effect. We show herein that expression of the GCH mutant GCH-201E or the splicing variant GCH-II caused intracellular inclusion bodies. When Hsp27 was expressed together with the GCH mutants, Hsp27 expression decreased the formation of inclusion bodies by GCH (as assessed by immunofluorescence) and decreased the amount of insoluble GCH mutant proteins (as assessed by Western blot). we demonstrated that Hsp27 increases the expression of the wild-type GCH protein, causes the appearance of the soluble GCH-II protein, and decreases the quantities of insoluble mutated GCH protein. Therefore, it is likely that Hsp27 improves the folding of mutated GCH proteins, so they can stay in free cytosolic compartment.	SIGNOR-252222

P25490

P07948

0

phosphorylation

down-regulates activity

0.2

In the case of Lyn overexpression, single mutations at either tyrosine 8, 254, or 383 severely reduced Lyn-mediated YY1 phosphorylation, suggesting that these three sites may be targets of Lyn in vivo (Fig. 3, A and B).

SIGNOR-276930

Q9BS26

Q86YB8

0

binding

up-regulates quantity by stabilization

0.2

Here, we report the functional characterization of a novel UPR-induced ER resident protein (ERp44) that forms mixed disulfides with both hEROs, as well as with partially unfolded Ig subunits.

SIGNOR-261048

Q99808

Q05655

0

phosphorylation

up-regulates activity

0.2

Phosphorylation of hENT1 by PKC has effects on both the function and subcellular trafficking of hENT1

SIGNOR-260888

Q9BR01

P27361

0

phosphorylation

down-regulates

0.2

The phosphorylation of sult4a1 allows interaction with pin1, which then promotes degradation of the sulfotransferase.

SIGNOR-168248

P84243

Q09472

0

acetylation

down-regulates activity

0.2

These results highlight the substrate and site specificities of hats in cells, demonstrate the distinct roles of gcn5/pcaf- and cbp/p300-mediated histone acetylations in gene activation, and suggest an important role of cbp/p300-mediated h3k18/27ac in nr-dependent transcription.

SIGNOR-170266

P02533

P06850

0

transcriptional regulation

down-regulates quantity by repression

0.2

CRH stimulated the expression of cytokeratin 1 and involucrin, and inhibited cytokeratin 14 on both mRNA and protein levels.

SIGNOR-251899

Q9Y4R8

P68400

0

phosphorylation

down-regulates

0.2

Here we report that tel2 and tti1 are targeted for degradation within mtorc1 by the scffbxo9 ubiquitin ligase to adjust mtor signalling to growth factor availability. This process is primed by ck2, which translocates to the cytoplasm to mediate mtorc1-specific phosphorylation of tel2/tti1. ere, we show that tel2 is constitutively phosphorylated on conserved serines 487 and 491 by casein kinase 2 (ck2)

SIGNOR-200202

O00257

Q9UNE7

0

ubiquitination

down-regulates quantity by destabilization

0.2

The phosphorylation of CBX4 at T437 by casein kinase 1α (CK1α) facilitated its ubiquitination at both K178 and K280 and subsequent degradation by CHIP, and this phosphorylation of CBX4 could be reduced by TNFα.

SIGNOR-277513

Q96PY5

P17252

0

phosphorylation

up-regulates activity

0.2

PKCα associates with and phosphorylates FMNL2 at S1072 within its Diaphanous autoregulatory region, leading to the release of formin autoinhibition.

SIGNOR-273796

P09471

Q9UNW8

0

binding

up-regulates activity

0.2

Here we systematically quantified ligand-induced interactions between 148 GPCRs and all 11 unique G alpha subunit C-termini. For each receptor, we probed chimeric G alpha subunit activation via a transforming growth factor-alpha (TGF alpha) shedding response in HEK293 cells lacking endogenous Gq/11- and G12/13- signaling. | We defined positive coupling if any member of the subfamily scored LogRAi ≥ -1 and negative coupling if all of the members scored LogRAi < -1 (Figure 3A-B). ROC analysis gives AUC = 0.78 (Figure S4A) when considering high-confidence known coupling data and suggested a threshold of LogRAi ≥ -1.0 for defining true couplings. | The score associated to this interaction has a LogRAi ≥ -1.0.

SIGNOR-257187

O43865

O15530

0

phosphorylation

down-regulates activity

0.2

Residue 68 resides in a consensus phosphorylation site for PKD (Figure 1A) [22,23]. Interestingly, phosphorylation of Ser68 could allow for subsequent phosphorylation of Ser71, Ser74, Ser77 and Ser80 by CK1, for which the consensus phosphorylation site is pS/T-X-X-S/T| We found that phosphorylation of Ser71 and Ser74 were sufficient to enable inhibition of IP3 binding to the IP3R

SIGNOR-249174

Q9NRC8

P61289

0

binding

down-regulates quantity by destabilization

0.2

Here, the authors show that energy stress induces an AMPK-dependent phosphorylation of Sirt7, which promotes its ubiquitin-independent degradation by REGγ, resulting in the down-regulation of rRNA transcription and cell survival.|These results strongly suggest that the phosphorylation status of SirT7 at T153 plays a crucial role in determining its subcellular distribution, degradation and binding to REGγ.

SIGNOR-275866

P35367

P17252

0

phosphorylation

down-regulates

0.2

In this study, we demonstrated that ser396 and ser398 are phosphorylated by pkc and, that phosphorylation of ser398 is particularly involved in pmainduced desensitization of the h1r.

SIGNOR-66015

P52630

Q7Z570

0

binding

up-regulates activity

0.2

Together these results indicate the formation of ZNF804A:STAT2 protein complex and its translocation from the cytoplasm into the nucleus upon IFN stimulation, suggesting that it may function as a signal transducer that activates IFN-mediated gene expression programs.

SIGNOR-269460

P21731-2

P35626

0

phosphorylation

down-regulates activity

0.2

These data suggest a model whereby agonist-induced PKC phosphorylation of Ser(145) partially impairs TPbeta signalling while GRK2/3 phosphorylation at both Ser(239) and Ser(357) within its IC(3) and C-tail domains, respectively, sterically inhibits G-protein coupling, profoundly desensitizing signalling, and promotes beta-arrestin association and, in turn, facilitates TPbeta internalization.

SIGNOR-274091

Q13148

O00311

0

phosphorylation

up-regulates activity

0.2

Among these, CDC7 directly phosphorylates TDP-43 on serines 409 and 410 both in vitro and in vivo .

SIGNOR-278256

P10636

Q9H992

0

ubiquitination

down-regulates activity

0.2

We have identified and characterized axotrophin, a protein that binds and preferentially mono-ubiquitinates tau protein.

SIGNOR-278655

Q9UN70

Q9Y5I2

0

binding

up-regulates activity

0.2

The clustered protocadherins comprise the largest subfamily of the cadherin superfamily and are predominantly expressed in the nervous system. Pcdh-alpha proteins interact with beta1-integrin to promote cell adhesion. They also form oligomers with Pcdh-gamma proteins at the same membrane sites.

SIGNOR-265696

Q13363

Q9BQ87

0

binding

down-regulates quantity by destabilization

0.2

TBL1 interacts in vivo with CtBP and promote its proteasomal degradation

SIGNOR-260902

Q03721

P05771

0

phosphorylation

down-regulates

0.2

We found that pkc specifically eliminates rapid inactivation of a cloned human a-type k+ channel (hkv3.4), converting this channel from a rapidly inactivating a type to a noninactivating delayed rectifier type.

SIGNOR-35626

Q9H808

Q96QT6

0

binding

up-regulates activity

0.2

We have cloned and characterized a new member of the PHD zinc finger family called Pf1 that interacts with two global transcription corepressors: mSin3A and TLE. Pf1 interacts with TLE. The Groucho/TLE proteins are members of an abundant corepressor family, and we hypothesized that Pf1 might interact with TLE family members. Together, these data suggest that in the absence of interactions with mSin3A, Gal4-Pf1 (102–273 L212P/A216P)-dependent repression can be attributed to interaction with endogenous TLE.

SIGNOR-266991

Q9Y2J4

P11362

0

phosphorylation

up-regulates activity

0.2

These data support an idea that Amotl2 Tyr-103 can be phosphorylated by FGF receptor tyrosine kinase activity. We then determined whether Amotl2 Tyr-103 is required for its interaction with c-Src. |Amotl2 promotes MAPK/ERK activation via c-Src, which is dependent on phosphorylation of tyrosine residue at position 103 but independent of the C-terminal PDZ-binding domain.

SIGNOR-271869

P68431

Q9UGL1

0

demethylation

up-regulates activity

0.2

KDM5 subfamily is capable of removing tri‐ and di‐ methyl marks from lysine 4 on histone H3 (H3K4). Depending on the methylation site, its effect on transcription can be either activating or repressing.

SIGNOR-264302

Q03113

O14842

0

binding

up-regulates activity

0.2

Here we systematically quantified ligand-induced interactions between 148 GPCRs and all 11 unique G alpha subunit C-termini. For each receptor, we probed chimeric G alpha subunit activation via a transforming growth factor-alpha (TGF alpha) shedding response in HEK293 cells lacking endogenous Gq/11- and G12/13- signaling. | We defined positive coupling if any member of the subfamily scored LogRAi ≥ -1 and negative coupling if all of the members scored LogRAi < -1 (Figure 3A-B). ROC analysis gives AUC = 0.78 (Figure S4A) when considering high-confidence known coupling data and suggested a threshold of LogRAi ≥ -1.0 for defining true couplings. | The score associated to this interaction has a LogRAi ≥ -1.0.

SIGNOR-257338

Q53GL7

P53350

0

phosphorylation

up-regulates activity

0.2

PLK1, an important regulator for cell mitosis, directly interacts with and phosphorylates PARP10 at T601. PARP10 phosphorylation at T601 significantly decreases its binding to NEMO and disrupts its inhibition to NEMO ubiquitination, thereby enhancing the transcription activity of NF-κB toward multiple target genes and promoting HCC development.

SIGNOR-273728

O43791

P53671

0

phosphorylation

down-regulates activity

0.2

LIMK2 phosphorylates SPOP at S59, S171 and S226.|Together, these results depict that LIMK2-mediated SPOP degradation is a key mechanism that regulates AR stability.

SIGNOR-278338

Q16695

P29375

0

demethylation

up-regulates activity

0.2

KDM5 subfamily is capable of removing tri‐ and di‐ methyl marks from lysine 4 on histone H3 (H3K4). Depending on the methylation site, its effect on transcription can be either activating or repressing.

SIGNOR-264300

P01100

P59595

0

transcriptional regulation

up-regulates quantity by expression

0.2

The transcription factors c-Fos, FosB, CREB-1, and ATF2 were all activated by the addition of SARS-CoV N protein to the sample well

SIGNOR-260726

Q13114

P0C6X7-PRO_0000037311

0

deubiquitination

down-regulates activity

0.2

Overexpressing PLPro of SARS-CoV or MERS-CoV significantly reduced the expression of IFN-Î² and proinflammatory cytokines in MDA5-stimulated 293T cells (83).Also, SARS-CoVPLPro catalyzed deubiquitination of TNF-receptor-associated factor3 (TRAF3) and TRAF6, thereby suppressing IFN-I and proinflammatory cytokines induced by TLR7 agonist (63). The deubiquitinating activity of SARS-CoV PLPro also suppressed a constitutively active phosphomimetic IRF3, suggesting its involvement in the postactivation signaling of IRF3

SIGNOR-260246

P54764

O00712

0

transcriptional regulation

up-regulates quantity

0.2

For example, within the NFI targetome, we identified 6 collagen genes, 13 genes encoding potassium channel or glutamate receptor subunits and a range of factors related to axon guidance (e.g. Slit1, Robo1, Epha4, Epha5, Epha8)

SIGNOR-268901

O14654

Q9UNE7

0

polyubiquitination

down-regulates quantity by destabilization

0.2

IRS4 was phosphorylated at Ser859 by CK1γ2 in vitro and in vivo, which promoted the polyubiquitination and degradation of IRS4 through the ubiquitin/lysosome pathway by the carboxyl terminus of Hsc70-interacting protein(CHIP).

SIGNOR-277616

Q14511

P30530

0

phosphorylation

up-regulates activity

0.2

Mechanistically, AXL phosphorylates NEDD9, leading to its binding to CRKII which in turn associates with and orchestrates the phosphorylation of the pseudo-kinase PEAK1.|These results reveal NEDD9 as a specific AXL substrate.We next validated whether AXL promotes canonical NEDD9 signaling.

SIGNOR-278905

P52945

P49841

0

phosphorylation

down-regulates quantity

0.2

We show that glucose levels modulate PDX1 protein phosphorylation at a novel C-terminal GSK3 consensus that maps to serines 268 and 272. A decrease in glucose levels triggers increased turnover of the PDX1 protein in a GSK3-dependent manner, such that PDX1 phosphomutants are refractory to the destabilizing effect of low glucose

SIGNOR-255566

O95471

Q13547

0

transcriptional regulation

down-regulates quantity by repression

0.2

ChIP assays revealed that SNAI1P is recruited on the CLDN7 gene promoter along with the co-repressor CtBP1 and the effector HDAC1.|These data further suggest that HDAC1 is involved in the SNAI1P-mediated repression of the human CLDN7 gene promoter.

SIGNOR-254106

P25098

P17612

0

phosphorylation

up-regulates activity

0.2

PKA directly phosphorylates GRK2 on serine 685. This modification increases G subunit binding to GRK2 and thus enhances the ability of the kinase to translocate to the membrane and phosphorylate the receptor.

SIGNOR-250334

Q96C90

Q05655

0

phosphorylation

up-regulates activity

0.2

Recombinant tagged PHI-1 was phosphorylated by protein kinase C at two sites, one a Ser and one a Thr; phosphorylation enhanced inhibitory potency 50-fold.

SIGNOR-265739

O15067

P28482

0

phosphorylation

up-regulates

0.2

T619 in PFAS is required to mediate ERK2-dependent purine synthesis stimulation. We demonstrate that ERK2, but not ERK1, phosphorylates the purine synthesis enzyme PFAS (phosphoribosylformylglycinamidine synthase) at T619 in cells to stimulate de novo purine synthesis. The expression of nonphosphorylatable PFAS (T619A) decreases purine synthesis, RAS-dependent cancer cell-colony formation, and tumor growth. Thus, ERK2-mediated PFAS phosphorylation facilitates the increase in nucleic acid synthesis required for anabolic cell growth and proliferation.

SIGNOR-267306

Q9UHD2

Q04759

0

phosphorylation

up-regulates activity

0.2

TBKBP1 recruits TBK1 to protein kinase C-theta (PKCθ) through a scaffold protein, CARD10. This enables PKCθ to phosphorylate TBK1 at Ser 716, a crucial step for TBK1 activation

SIGNOR-272472

Q13526

P45984

0

phosphorylation

up-regulates quantity by stabilization

0.2

Mechanistically, the JNK kinases directly bind to and phosphorylate PIN1 at Ser115, and this phosphorylation prevents PIN1 mono-ubiquitination at Lys117 and its proteasomal degradation.

SIGNOR-277563

O00548

P51608

0

transcriptional regulation

down-regulates quantity by repression

0.2

As the first step to reveal how MeCP2 phosphorylation may regulate Notch signaling, we conducted chromatin immunoprecipitation (ChIP) experiment to determine whether the phosphor-mutant MeCP2 protein has altered promoter occupancy at the promoters of Dll1 and Notch1. We found increased binding of the phosphor-mutant protein at the promoters of both Dll1 and Notch1

SIGNOR-264674

P36888

Q14469

0

transcriptional regulation

down-regulates quantity by repression

0.2

We then found that Hes1 directly bound to the promoter region of the FMS-like tyrosine kinase 3 (FLT3) gene and downregulated the promoter activity.

SIGNOR-261563

Q9NR31

Q9NRC8

0

deacetylation

up-regulates activity

0.2

SIRT7 interacts with the helicase DDX21. Deacetylation by SIRT7 is required for DDX21 activity and R-loop unwinding

SIGNOR-260978

P42336

O95819

0

phosphorylation

down-regulates activity

0.2

MST1/2 and HGK inhibit catalytic activity of p110α through phosphorylation at T1061

SIGNOR-277921

Q9Y261

O15111

0

phosphorylation

down-regulates

0.2

Here, we show that ikk_, an important downstream kinase of tnf_, interacts with and phosphorylates foxa2 at s107/s111, thereby suppressing foxa2 transactivation activity and leading to decreased numb expression

SIGNOR-195316

Q13363

Q13131

0

phosphorylation

down-regulates

0.2

We found that an activated amp-activated protein kinase (ampk) phosphorylates ctbp1 on ser-158 upon metabolic stresses. Moreover, ampk-mediated phosphorylation of ctbp1 (s158) attenuates the repressive function of ctbp1

SIGNOR-200250

P25208

P78317

0

binding

up-regulates activity

0.2

Coactivator RNF4 is involved in the GCH gene expression. Through serial deletion and mutagenesis studies of the GCH promoter, we defined the RNF4-responsive element on GCH proximal promoter as a CCAAT box. RNF4 did not possess specific DNA binding activity toward this CCAAT box, which suggests that RNF4 may be a coactivator of the CCAAT boxbinding protein nuclear factor Y (NF-Y). RNF4 is a coactivator for nuclear factor Y on GTP cyclohydrolase I proximal promoter.

SIGNOR-252230

P63092

Q96P68

0

binding

up-regulates activity

0.2

Here we systematically quantified ligand-induced interactions between 148 GPCRs and all 11 unique G alpha subunit C-termini. For each receptor, we probed chimeric G alpha subunit activation via a transforming growth factor-alpha (TGF alpha) shedding response in HEK293 cells lacking endogenous Gq/11- and G12/13- signaling. | We defined positive coupling if any member of the subfamily scored LogRAi ‚â• -1 and negative coupling if all of the members scored LogRAi < -1 (Figure 3A-B). ROC analysis gives AUC = 0.78 (Figure S4A) when considering high-confidence known coupling data and suggested a threshold of LogRAi ‚â• -1.0 for defining true couplings. | The score associated to this interaction has a LogRAi ‚â• -1.0.

SIGNOR-256770

P09471

Q99677

0

binding

up-regulates activity

0.2

Here we systematically quantified ligand-induced interactions between 148 GPCRs and all 11 unique G alpha subunit C-termini. For each receptor, we probed chimeric G alpha subunit activation via a transforming growth factor-alpha (TGF alpha) shedding response in HEK293 cells lacking endogenous Gq/11- and G12/13- signaling. | We defined positive coupling if any member of the subfamily scored LogRAi ≥ -1 and negative coupling if all of the members scored LogRAi < -1 (Figure 3A-B). ROC analysis gives AUC = 0.78 (Figure S4A) when considering high-confidence known coupling data and suggested a threshold of LogRAi ≥ -1.0 for defining true couplings. | The score associated to this interaction has a LogRAi ≥ -1.0.

SIGNOR-257258

P02675

P45452

0

cleavage

down-regulates quantity by destabilization

0.2

Matrix metalloproteinases collagenase-2, macrophage elastase, collagenase-3, and membrane type 1-matrix metalloproteinase impair clotting by degradation of fibrinogen and factor XII| We have now investigated the role of collagenase-2 (MMP-8), macrophage elastase (MMP-12), collagenase-3 (MMP-13), and membrane type 1-matrix metalloproteinase (MT1-MMP, MMP-14) in the degradation of fibrinogen and Factor XII of the plasma clotting system.|MMP-13 27YVATRDN g-chain| 20ADSGEGD a-chain| 124RNSVDXLNXN b-chain| 442LRTGKEKV a-chain

SIGNOR-263615

P0DPK2

Q92831

0

acetylation

down-regulates activity

0.2

The HAT module within the SAGA and ADA complexes acetylates histone H3, mainly on residues K9 and K14.

SIGNOR-269614

Q92820

P08047

0

transcriptional regulation

up-regulates quantity by expression

0.2

Overexpression of Sp1 led to enhanced GGH promoter activity and GGH mRNA expression in allele-specific manners. These findings suggested that Sp1 acted as a positive regulator of human GGH transcription through the rs3758149 polymorphism in CEM/C1 cells.

SIGNOR-261350

Q96SR6

Q8NFU7

0

transcriptional regulation

up-regulates quantity by expression

0.2

Furthermore, TET1 catalytic domain possessed demethylase activity in cancer cells, being able to inhibit the CpG methylation of tumor suppressor gene (TSG) promoters and reactivate their expression, such as SLIT2, ZNF382 and HOXA9.

SIGNOR-259095

O14920

Q9Y5X2

0

binding

up-regulates activity

0.2

IFNγ induced JAK1-mediated phosphorylation of SNX8 at Tyr95 and Tyr126, which promoted the recruitment of IKKβ to the JAK1 complex.

SIGNOR-273646

P21730

Q05655

0

phosphorylation

down-regulates

0.2

Whole cell phosphorylation assays with specific inhibitors as well as in vitro phosphorylation assays with recombinant enzymes and peptide substrates revealed that phosphorylation of ser-334 is regulated by protein kinase c-beta this study is among the first to analyze in a detailed manner, using a non-mutational approach, modifications of a defined phosphorylation site in a g protein-coupled receptor and to correlate these findings with functional parameters of receptor deactivation.

SIGNOR-73967

Q13017

Q13882

0

phosphorylation

up-regulates

0.2

Breast tumor kinase phosphorylates p190rhogap to regulate rho and ras and promote breast carcinoma growth, migration, and invasion. Brk phosphorylates p190 at the y(1105) residue both in vitro and in vivo, thereby promoting the association of p190 with p120rasgap (p120). As a consequence, brk stimulates p190 and attenuates p120 functions, leading to rhoa inactivation and ras activation, respectively.

SIGNOR-181452

Q6PKG0

P24941

0

phosphorylation

up-regulates activity

0.2

CDK2 phosphorylates LARP1 protein, regulates TOP-protein expression and LARP1\u2019s translational activity.

SIGNOR-279015

Q16873

P23443

0

phosphorylation

down-regulates activity

0.2

Here, we identified Ser(36) as the major p70S6k phosphorylation site, along with a low frequency site at Thr(40), using an in vitro phosphorylation assay combined with mass spectrometry. Cellular LTC4S activity is suppressed by PKC-mediated phosphorylation, and recently a downstream p70S6k was shown to play an important role in this process.

SIGNOR-277256

Q06210

Q13131

0

phosphorylation

down-regulates

0.2

Amp-activated protein kinase phosphorylates glutamine : fructose-6-phosphate amidotransferase 1 at ser243 to modulate its enzymatic activityhe 2-dg induced phosphorylation of gfat1 . The assay of the gfat enzymatic activity in the cell lysates indicated that the 2-dg-treatment inhibited the enzymatic activity

SIGNOR-183528

P07288

Q02447

0

transcriptional regulation

up-regulates quantity by expression

0.2

We characterized four Sp1/Sp3 binding sites in the proximal promoter of the PSA gene. In a luciferase assay, these sites contributed to the basal promoter activity in prostate cancer cells. In an electrophoretic mobility shift assay and chromatin immunoprecipitation assay, we confirmed that Sp1 and Sp3 bind to these sites. Overexpression of wild-type Sp1 and Sp3 further upregulated the promoter activity, whereas overexpression of the Sp1 dominant-negative form or addition of mithramycin A significantly reduced the promoter activity and the endogenous mRNA level of PSA.

SIGNOR-253665

O95243

P17252

0

phosphorylation

up-regulates activity

0.2

Phosphorylation of MBD4 promotes 5-meC glycosylase activity Further evidence emerged to support the involvement of MBD4 in active demethylation. Protein-kinase C phosphorylation of MBD4 at two specific serine residues (165 and 262) following parathyroid hormone stimulation was shown to promote demethylation within the CYP27B1 gene promoter [12]

SIGNOR-275672

Q93008

O60729

0

dephosphorylation

down-regulates quantity by destabilization

0.2

Here, we find that CDC14B antagonizes CDK1-mediated activating mitotic phosphorylation of the deubiquitinase USP9X at serine residue 2563, which we show to be essential for USP9X to mediate mitotic survival. Starting from an unbiased proteome-wide screening approach, we specify Wilms' tumor protein 1 (WT1) as the relevant substrate that becomes deubiquitylated and stabilized by serine 2563-phosphorylated USP9X in mitosis.

SIGNOR-275613

Q02880

P48730

0

phosphorylation

down-regulates quantity by destabilization

0.2

Specifically, DNA damage signal, triggered by teniposide (VM-26) treatment, activates ATM, cooperating with CK1 to phosphorylate TOP2β on Ser1134 and Ser1130, respectively, in a canonical degron motif to facilitate β-TrCP binding and subsequent degradation.CK1 binds with and phosphorylates TOP2β at Ser1130 to promote its degradation by VM-26.

SIGNOR-277509

Q12913

P68400

0

phosphorylation

up-regulates activity

0.2

CK2-dependent phosphorylation of DEP-1 T1318 promotes Y1320 phosphorylation and Src activation upon VEGF stimulation.

SIGNOR-277876

Q8IX03

P51812

0

phosphorylation

up-regulates

0.2

Moreover, we found that rsk1/2 specifically phosphorylates kibra at two highly conserved sites (thr(929) and ser(947)) in vitro and in cells. Rsk-mediated phosphorylation is required for kibra binding to rsk1, but not rsk2.

SIGNOR-203302

Q71DI3

Q14493

0

translation regulation

up-regulates quantity by expression

0.2

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

SIGNOR-265414

P48730

Q5T0W9

0

binding

up-regulates quantity

0.2

We identified members of the FAM83 family of proteins as partners of CK1 in cells. All eight members of the FAM83 family (FAM83A–H) interacted with the α and α-like isoforms of CK1; FAM83A, -B, -E, and -H also interacted with the δ and ε isoforms of CK1. The intrinsic catalytic activity of CK1 is not affected by or required for the association of CK1 with FAM83 proteins. Our findings imply that the DUF1669 domains of FAM83 proteins anchor CK1 α, α-like, δ, and ε isoforms in specific subcellular compartments and potentially mediate their association with substrates.

SIGNOR-273766

P01574

P03209

0

transcriptional regulation

down-regulates quantity by repression

0.2

Epstein-Barr Virus BRLF1 Inhibits Transcription of IRF3 and IRF7 and Suppresses Induction of Interferon-β. These results suggest that EBV Rta is capable of regulating the activation of the IFN-β promoter.

SIGNOR-266646

Q8TE73

Q96M91

0

binding

up-regulates activity

0.2

CFAP53 likely facilitates the transport of TTC25 and the dyneins into cilia. CFAP53 at the centriolar satellites may form a complex with TTC25 and ODAs, including DNAH5 and DNAH11, and regulate their trafficking into the cilium (Fig 10B).

SIGNOR-265544

P35222

Q9H1B7

0

ubiquitination

down-regulates quantity by destabilization

0.2

FOXF2 directly bound the promoter of E3 ligase interferon regulatory factor 2-binding protein-like (IRF2BPL) and induced its transcriptional expression. IRF2BPL in turn interacted with β-catenin, increasing its ubiquitination and degradation.

SIGNOR-267153

P15036

Q9UQM7

0

phosphorylation

down-regulates

0.2

Camkii caused ets-2 phosphorylation.Serine 246, 310, and 313 were the targets. Camkii to phosphorylates ets-2, thus altering ets-2 binding to its downstream promoters

SIGNOR-183596

P62879

Q99835

0

binding

up-regulates

0.2

Consistent with its predicted topology, smo couples to a specific family of inhibitory g protein (gis) to regulate hh signaling.

SIGNOR-199177

P38117

Q8IXQ9

0

methylation

down-regulates activity

0.2

Accordingly, we found that METTL20-mediated methylation of ETFβ in vitro reduced its ability to receive electrons from the medium chain acyl-CoA dehydrogenase and the glutaryl-CoA dehydrogenase. In conclusion, the present study establishes METTL20 as the first human KMT localized to mitochondria and suggests that it may regulate cellular metabolism through modulating the interaction between its substrate ETFβ and dehydrogenases.

SIGNOR-269450

P43629

P05129

0

phosphorylation

down-regulates

0.2

Functional studies of the wild-type receptor and serine/threonine mutants indicated that phosphorylation of ser(394) by protein kinase c slightly suppresses kir3dl1 inhibitory function, and reduces receptor internalization and turnover.

SIGNOR-158133

Q13541

P49674

0

phosphorylation

down-regulates

0.2

Mechanistic investigations showed that ck1_ interacted with and phosphorylated 4e-bp1 at two novel sites t41 and t50, which were essential for 4e-bp1 inactivation along with increased mrna translation and cell proliferation.

SIGNOR-203240

P49959

P53350

0

phosphorylation

down-regulates activity

0.2

Plk1 phosphorylates Mre11 at S649.Mre11 phosphorylation at S649/S688 inhibits its binding to dsDNA and antagonizes the ATM signaling.

SIGNOR-265943

P35236

Q15139

0

phosphorylation

up-regulates activity

0.2

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

SIGNOR-276046

Q92952

P00533

0

phosphorylation

up-regulates activity

0.2

These results demonstrate the novel information that hSKCa1 channels are inhibited by genistein, T25 and AG556 via EGFR tyrosine kinase inhibition, which is related to the phosphorylation of Tyr(109) in the N-terminus.

SIGNOR-276490

P01189-PRO_0000024969

P16519

0

cleavage

up-regulates quantity

0.2

POMC is post-translationally cleaved by prohormone convertase enzymes 1 and 2 (PC1, PC2) into ACTH, an N-terminal glycopeptide

SIGNOR-268725

P68871

P15289

0

acetylation

up-regulates activity

0.2

ASA acetylates hemoglobin. Purified acetylated hemoglobin had a slightly increased oxygen affinity and decreased heme-heme interaction.

SIGNOR-251772

P05556

Q9UN74

0

binding

up-regulates activity

0.2

The clustered protocadherins comprise the largest subfamily of the cadherin superfamily and are predominantly expressed in the nervous system. Pcdh-alpha proteins interact with beta1-integrin to promote cell adhesion.

SIGNOR-265665

P68431

O15550

0

demethylation

down-regulates activity

0.2

Ubiquitously Transcribed Tetratricopeptide Repeat on chromosome X (UTX) and Jumonji D3 (JMJD3) as novel histone demethylases that catalyze the removal of di- and trimethyl groups on histone H3 lysine 27, thereby promoting target gene activation.

SIGNOR-260017

Q9C0B5

P04637

0

transcriptional regulation

up-regulates quantity by expression

0.2

Mechanistic investigations revealed that mutant p53 transcriptionally upregulated ZDHHC5 along with the nuclear transcription factor NF-Y

SIGNOR-261150

P23769

Q5D1E8

0

post transcriptional regulation

up-regulates quantity

0.2

Here, we show that Regnase-1 regulates self-renewal of HSPCs through modulating the stability of Gata2 and Tal1 mRNA

SIGNOR-259943

P32004

P17252

0

phosphorylation

down-regulates activity

0.2

CKII phosphorylates T1172 of the L1 CD and phosphorylation of T1172 is responsible for loss of 2C2 signal.

SIGNOR-276283

P19484

P11802

0

phosphorylation

up-regulates activity

0.2

CDK4 and CDK6 phosphorylate TFEB and TFE3.

SIGNOR-279450

Q8IW41

Q9UKI8

0

phosphorylation

up-regulates activity

0.2

We established that TLK1 phosphorylates MK5 on three residues (S160, S354 and S386), resulting in MK5 activation, and additionally, mobility shifts of MK5 also supported its phosphorylation by TLK1 in transfected HEK 293 cells.

SIGNOR-276747

Q9Y5G6

Q9Y5I2

0

binding

up-regulates activity

0.2

The clustered protocadherins comprise the largest subfamily of the cadherin superfamily and are predominantly expressed in the nervous system. Pcdh-alpha proteins interact with beta1-integrin to promote cell adhesion. They also form oligomers with Pcdh-gamma proteins at the same membrane sites.

SIGNOR-265709

P84243

P83916

0

binding

up-regulates activity

0.2

A core characteristic of heterochromatin is its association with heterochromatin protein 1 (HP1) proteins, a highly conserved family of chromosomal proteins that bind to di- and trimethylated H3K9 via a conserved N-terminal domain called the chromodomain (CD) HP1 proteins are a highly conserved family of eukaryotic proteins that bind to methylated histone H3 lysine 9 (H3K9) and are required for heterochromatic gene silencing.

SIGNOR-264491

Q6NXT2

Q14493

0

translation regulation

up-regulates quantity by expression

0.2

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

SIGNOR-265420

O43896

Q6ZP65

0

binding

up-regulates activity

0.2

BICDR-1 interacts with the dynein/dynactin motor complex. In young neurons, BICDR-1 accumulates Rab6 secretory vesicles around the centrosome, restricts anterograde secretory transport and inhibits neuritogenesis. Later during development, BICDR-1 expression is strongly reduced, which permits anterograde secretory transport required for neurite outgrowth. These results indicate an important role for BICDR-1 as temporal regulator of secretory trafficking during the early phase of neuronal differentiation. These results show that BICDR-1 regulates recruitment and/or activity of the anterograde kinesin motor Kif1C on Rab6 secretory carriers.

SIGNOR-266876

P84243

Q9UPS6

0

methylation

down-regulates activity

0.2

SETD1B encodes a lysine-specific methyltransferase that assists in transcriptional activation of genes by depositing H3K4 methyl marks.

SIGNOR-265578

Q9BXH1

Q92570

0

transcriptional regulation

up-regulates quantity by expression

0.2

Over-expression of NR4A3 attenuated proliferation of cancer cells and promoted apoptosis by augmenting the expression of pro-apoptotic genes, PUMA and Bax.

SIGNOR-259396

P48426

Q15139

0

phosphorylation

down-regulates

0.2

We conclude that the type ii pip kinases are physiological targets for pkd phosphorylation, and that this modification is likely to regulate inositol lipid turnover by inhibition of these lipid kinases.

SIGNOR-145370

Q5TEC6

Q9NRC8

0

deacetylation

up-regulates activity

0.2

Besides confirming the previously reported histone H3K18 deacylation activity, our results revealed that SIRT7 has an astonishingly high activity to catalyze deacylation of H3K36 and is also catalytically active to deacylate H3K37.

SIGNOR-275883

Q15109

Q13315

0

phosphorylation

up-regulates activity

0.2

RAGE is phosphorylated at Serine 376 and Serine 389 by the ATM kinase and is recruited to the site of DNA-DSBs via an early DNA damage response.

SIGNOR-278907

Q99250

Q8NEV1

0

phosphorylation

up-regulates activity

0.2

We found that the ankyrin-binding motif of Na(v)1.2 that determines channel concentration at the AIS depends on a glutamate residue (E1111), but also on several serine residues (S1112, S1124, and S1126). We showed that phosphorylation of these residues by protein kinase CK2 (CK2) regulates Na(v) channel interaction with ankyrins. | inhibition of CK2 activity reduced sodium channel accumulation at the AIS of neurons. In conclusion, CK2 contributes to sodium channel organization by regulating their interaction with ankyrin G.

SIGNOR-275755

O95243

P63279

0

sumoylation

up-regulates activity

0.2

MBD4 is sumoylated at three main sites: K137, K215 and K377.|Sumoylation increases the G:T repair activity of MBD4 in cell extracts.|we conducted an in vitrosumoylation assay, employing recombinant activating E1 (Aos1-Uba2) and conjugating E2 (Ubc9) enzymes, along with recombinant YFP-SUMO1 and MBD4 or, as positive control for sumoylation, TDG (Fig. 2D). These results indicate that MBD4 is sumoylated in vivo and in vitro.

SIGNOR-275678

P04628

P11308

0

transcriptional regulation

up-regulates quantity by expression

0.2

Interestingly, our data showed that ERG drastically induced Wnt ligand gene expression.

SIGNOR-261597

P38405

P47900

0

binding

up-regulates activity

0.2

Here we systematically quantified ligand-induced interactions between 148 GPCRs and all 11 unique G alpha subunit C-termini. For each receptor, we probed chimeric G alpha subunit activation via a transforming growth factor-alpha (TGF alpha) shedding response in HEK293 cells lacking endogenous Gq/11- and G12/13- signaling. | We defined positive coupling if any member of the subfamily scored LogRAi ≥ -1 and negative coupling if all of the members scored LogRAi < -1 (Figure 3A-B). ROC analysis gives AUC = 0.78 (Figure S4A) when considering high-confidence known coupling data and suggested a threshold of LogRAi ≥ -1.0 for defining true couplings. | The score associated to this interaction has a LogRAi ≥ -1.0.

SIGNOR-256943

P30793

P04792

0

binding

up-regulates quantity by stabilization

0.2

GTP cyclohydrolase I (GCH), an oligomeric protein composed of 10 identical subunits, is required for the synthesis of neurotransmitters; mutations in GCH are associated with dopa-responsive dystonia (DRD) and hyperphenylalaninemia. Mutated GCH proteins are unstable and prone to dominant-negative effect. We show herein that expression of the GCH mutant GCH-201E or the splicing variant GCH-II caused intracellular inclusion bodies. When Hsp27 was expressed together with the GCH mutants, Hsp27 expression decreased the formation of inclusion bodies by GCH (as assessed by immunofluorescence) and decreased the amount of insoluble GCH mutant proteins (as assessed by Western blot). we demonstrated that Hsp27 increases the expression of the wild-type GCH protein, causes the appearance of the soluble GCH-II protein, and decreases the quantities of insoluble mutated GCH protein. Therefore, it is likely that Hsp27 improves the folding of mutated GCH proteins, so they can stay in free cytosolic compartment.

SIGNOR-252222