GleghornLab/Signor_3class · Datasets at Hugging Face

IdA stringlengths 6 21	IdB stringlengths 6 21	labels int64 0 2	mechanism stringclasses 40 values	effect stringclasses 10 values	score float64 0.1 0.99 ⌀	sentence stringlengths 10 1.63k ⌀	signor_id stringlengths 12 14
Q8IWS0	P17480	2	binding	down-regulates	0.28	We demonstrate that phf6 is a nucleolus, ribosomal rna promoter-associated protein. Phf6 directly interacts with upstream binding factor (ubf) through its phd1 domain and suppresses ribosomal rna (rrna) transcription by affecting the protein level of ubf	SIGNOR-200133
P35968	P23470	0	dephosphorylation	down-regulates activity	0.253	PTPRG activation by the P1-WD peptide affected the tyrosine phosphorylation of several signaling molecules. Data analysis identified 31 molecules whose phosphorylation was modified in a statistically significant manner (Table I). inhibition of ABL1, BMX, BTK, DAB1, ITGB1, JAK2, KDR, KIT, LIMK1, MET, PDGFRB, SHC1, and VCL correlates with tyrosine dephosphorylation. In contrast, SRC inhibition correlates with hyperphosphorylation of the inhibitory Tyr530 residue and with dephosphorylation of the activatory Tyr419. Moreover, CDK2 and CTTN inhibition correlates with a hyperphosphorylation of the inhibitory Tyr15 and Tyr470, respectively. In contrast, a subgroup of 13 proteins, including BLNK, DOK2, ERBB2, GRIN2B, INSR, PDGFRA, PRKCD, PXN, STAT1, STAT2, STAT3, STAT5A, and ZAP70, appears to be activated by PTPRG activity.	SIGNOR-254707
P41440	P17676	0	transcriptional regulation	up-regulates quantity by expression	0.2	Collectively, these results identify transcriptionally important regions in the hRFC-C minimal promoter that include a GC-box and CCAAT-box, and suggest that cooperative interactions between Sp1 and C/EBP beta are essential for hRFC-C transactivation.	SIGNOR-254053
Q13351	P42773	1	transcriptional regulation	up-regulates quantity by expression	0.266	Thus, EKLF is a direct regulator of p18INK4c gene expression, and much of EKLF's role in driving erythroid cell differentiation may occur via p18INK4c.	SIGNOR-266046
O43683	Q9Y6D9	1	relocalization	up-regulates activity	0.727	Spindle checkpoint protein Bub1 is required for kinetochore localization of Mad1, Mad2, Bub3, and CENP-E, independently of its kinase activity	SIGNOR-252017
Q15762	Q92692	2	binding	up-regulates activity	0.2	CD226 (DNAM-1) is an adhesion molecule involved in NK and T cell-mediated cytotoxicity against certain tumors. Here, we have identified the human poliovirus receptor-related (PRR) family members CD155 [poliovirus receptor (PVR)] and CD112 (nectin-2/PRR-2) as the ligands for human CD226.	SIGNOR-261426
P42127	P41968	2	binding	down-regulates activity	0.511	The melanocortin (MC) receptor family consists of five Gs-coupled receptors that control various physiological functions in response to four distinct agonists, adrenocorticotropic hormone (ACTH, also known as corticotrophin) and alpha, beta, and gamma melanocyte-stimulating hormone (MSH), which are derived from the proopiomelanocortin precursor protein, and two inverse agonists, agouti and agouti-related proteins	SIGNOR-268703
P78317	P29590	1	polyubiquitination	down-regulates quantity by destabilization	0.487	Upon TGF-β induction, interaction of Arkadia with phosphorylated Smad2 triggers degradation of SnoN, whereas upon arsenic treatment, interaction of Arkadia with poly-SUMO in PML nuclear bodies induces degradation of polysumoylated PML together with RNF4.	SIGNOR-272884
P42338	P01111	2	binding	up-regulates	0.668	Grb2 binds and activates sos, which then activates ras, and this activates p110 independently of p85./it was also described that ras interacts with pi3k in a direct manner./lysine residue 227 is essential for the interaction of ras with pi3k	SIGNOR-175225
P35442	Q08722	2	binding	up-regulates	0.592	We report here that iap is a receptor for the ts1 cbd and its vvm-containing peptides and that a function-blocking anti-iap mab inhibits the chemotactic response to ts1 and its cbd peptides in endothelial cells.	SIGNOR-39749
Q17RY0	P28482	0	phosphorylation	up-regulates activity	0.325	Our results indicate that CPEB4 activation is driven by ERK2- and Cdk1 mediated hyperphosphorylation of at least 12 residues in the intrinsically disordered NTD.\|We concluded that, in interphase, unphosphorylated CPEB4 phase separates into liquid like droplets that recruit mRNAs but are inactive for cytoplasmic polyadenylation and translation, whereas in M-phase, CPEB4 is phosphorylated by ERK2 and Cdk1 and recovers its monomeric form, which can drive the cytoplasmic polyadenylation of target mRNAs.	SIGNOR-280021
Q9UQ26	O14795	1	relocalization	up-regulates activity	0.358	N-terminal interactions of RIMs with RAB3 and MUNC13 regulate DCV fusion. Through N-terminal interactions, RIMs position MUNC13 and recruit DCVs via RAB3, which is located on the vesicle	SIGNOR-264383
P49841	Q9NZQ7	1	phosphorylation	down-regulates quantity by destabilization	0.307	We show that glycogen synthase kinase 3β (GSK3β) interacts with PD-L1 and induces phosphorylation-dependent proteasome degradation of PD-L1 by β-TrCP.	SIGNOR-277275
Q92918	P07948	0	phosphorylation	up-regulates activity	0.381	BCR ligation induced rapid tyrosine-phosphorylation of HPK1 mainly by Syk and Lyn, resulting in its association with BASH and catalytic activation. Tyr-379 within HPK1 is essential for binding to BASH and thus strongly suggest that the DDDYDDV sequence containing the phosphorylated Tyr-379 is the binding site for the BASH SH2 domain.	SIGNOR-251403
Q16539	P52564	0	phosphorylation	up-regulates activity	0.744	These data indicate that mkk6 phosphorylates p38 map kinase on thr-180 and tyr-182, the sites of phosphorylation that activate p38 map kinase	SIGNOR-40427
P35354	O95644	0	transcriptional regulation	up-regulates quantity by expression	0.316	NFAT induces the transcription of the COX2 (cyclo-oxygenase-2) gene incancer cells thereby enhancing invasive migration	SIGNOR-264026
P46020	P17612	0	phosphorylation	up-regulates activity	0.432	Phosphorylation of the alpha and beta subunits by the 3',5'-cyclic adenosine monophosphate (cAMP)-dependent protein kinase (PKA) also relieves inhibition of the gamma subunit and thereby activates the enzyme.	SIGNOR-267411
P01106	P11166	1	transcriptional regulation	up-regulates quantity	0.43	C-Myc directly transactivates genes encoding GLUT1, phosphofructokinase, and enolase and increases glucose uptake in Rat1 fibroblasts. Nuclear run-on studies confirmed that the GLUT1 transcriptional rate is elevated by c-Myc. Our findings suggest that overexpression of the c-Myc oncoprotein deregulates glycolysis through the activation of several components of the glucose metabolic pathway.	SIGNOR-259987
Q00987	Q9H0A0	0	ubiquitination	down-regulates quantity by destabilization	0.33	NAT10 acetylates p53 at K120 and stabilizes p53 by counteracting Mdm2 action. In addition, NAT10 promotes Mdm2 degradation with its intrinsic E3 ligase activity.	SIGNOR-272405
P30793	O95433	2	binding	up-regulates activity	0.297	The interaction of GCH1 with Aha1 may recruit GCH1 into the eNOS/Hsp90 complex so as to support local changes in nitric oxide production by endothelial cells.	SIGNOR-252213
P36956	P14618	1	transcriptional regulation	up-regulates quantity by expression	0.29	Well-described targets of srebp-1 and the carbohydrate response element binding protein (chrebp), which include the following: fatty acid synthase (fas), acetyl coa carboxylase (acc1), and liver pyruvate kinase (l-pk)	SIGNOR-166381
P16949	Q9UQM7	0	phosphorylation	down-regulates	0.403	Involved in the regulation of the microtubule (mt) filament system by destabilizing microtubules. Prevents assembly and promotes disassembly of microtubules. In vitro, ser16 of recombinant human stathmin was phosphorylated also by purified cam kinase ii, and in vivo, cam kinase ii activity was indeed stimulated in cd2-triggered jurkat cells. Altogether, our results favor an association of cam kinase ii activity with costimulatory signals of t lymphocyte activation and phosphorylation of stathmin on ser16.	SIGNOR-149640
Q16288	P19174	2	binding	up-regulates	0.619	Unglycosylated trka core protein is phosphorylated even in the absence of ligand stimulation and displays constitutive kinase activity as well as constitutive interaction with the signaling molecules shc and plc-gamma.	SIGNOR-67404
Q9BXW9	O14757	0	phosphorylation	up-regulates activity	0.585	In vitro and in vivo experiments show that phosphorylation of s331 is mediated by chk1, the s-phase checkpoint kinase implicated in the fanconi anemia dna repair pathway. phosphorylation at this site is dependent on chk1, signifying the importance of the s-phase checkpoint in the activation of fanconi anemia pathway.	SIGNOR-107042
P17252	P04049	1	phosphorylation	down-regulates	0.558	Pka can inhibit raf-1 function directly via phosphorylation of the raf-1 kinase domain	SIGNOR-34761
P46937	Q15208	0	phosphorylation	down-regulates activity	0.383	We show that mammalian NDR1/2 kinases phosphorylate YAP1 on S127 and thereby negatively regulate YAP1 activity in tissue-cultured cells.	SIGNOR-259855
P48730	P11308	1	phosphorylation	down-regulates activity	0.2	Interestingly, only CKId, but not other CKI isoforms or CKII could promote ERG degradation under ectopic expression conditions (XREF_FIG).\|These results indicate that phosphorylation of ERG by CKIdelta within the SPOP-recognition degron triggers its interaction with SPOP to promote ERG destruction .	SIGNOR-280234
Q04206	Q99576	2	binding	down-regulates activity	0.373	GILZ inhibits NF-kappaB nuclear translocation and DNA binding due to a direct protein-to-protein interaction of GILZ with the NF-kappaB subunits.	SIGNOR-253297
P06850	P10275	0	transcriptional regulation	down-regulates quantity by repression	0.305	A direct androgenic involvement in the expression of human corticotropin-releasing hormone\|A potential androgen-responsive element (ARE) in the human CRH promoter was subsequently analyzed with bandshifts and cotransfections in neuroblastoma cells. In the presence of testosterone, recombinant human AR bound specifically to the CRH-ARE.	SIGNOR-268723
O43521	Q16611	2	binding	up-regulates	0.837	Bim, and puma bind with high affinity to all pro-survival proteins	SIGNOR-196932
O95644	P35354	1	transcriptional regulation	up-regulates quantity by expression	0.316	NFAT induces the transcription of the COX2 (cyclo-oxygenase-2) gene incancer cells thereby enhancing invasive migration	SIGNOR-264026
P31751	P49840	1	phosphorylation	down-regulates	0.557	Activated pi3k/akt pathway results in inhibitory phosphorylation of gsk3	SIGNOR-138179
P53355	P19105	1	phosphorylation	up-regulates activity	0.275	DAPK Phosphorylates Myosin II RLC in Vitro and in Vivo. Together these results show that similar to the conventional MLCKs, Ser-19 is the primary RLC residue phosphorylated by DAPK and that phosphorylation of Thr-18 is also possible.	SIGNOR-262842
Q8TB45	Q15418	0	phosphorylation	down-regulates	0.492	We found that deptor was rapidly phosphorylated on three serines in a conserved degron, facilitating binding and ubiquitylation by the f box protein _trcp, with consequent proteasomal degradation of deptor. Phosphorylation of the _trcp degron in deptor is executed by ck1	SIGNOR-176883
Q99880	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-265389
Q7KZF4	P42226	2	binding	up-regulates activity	0.479	STAT6 interacted with p100 in vitro and in vivo. Here, we show that the TAD of STAT6 is interacting with p100. p100 was found to enhance the STAT6-mediated transcription [.].	SIGNOR-259134
Q9H4G4	P51617	0	phosphorylation	up-regulates activity	0.325	We found that TIRAP-MyD88 dependent kinase IRAK1 phosphorylated GAPR-1 at Serine 58 site. The phosphorylation of GAPR-1 promoted its interaction with TRAM-TRIF dependent inhibitor TMED7, and impaired TMED7-mediated disruption of the TRAM-TRIF complex to trigger IFN-β and the IL10 secretion.	SIGNOR-262887
Q9UKT5	P49841	0	phosphorylation	up-regulates	0.2	Gsk3beta-mediated phosphorylation of fbx4 ser12 during the g1/s transition regulates fbx4 dimerization, which in turn governs fbx4-driven e3 ligase activity.	SIGNOR-171648
P02671	P50281	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-14 27YVATRDN g-chain\| 105XDAATLKSR g-chain \| 92LTYNPDES g-chain \|105LTTNIXEXL a-chain\|433LVTSKGDKE a-chain\| 117FXSANNRD a-chain	SIGNOR-263620
Q99558	P11413	1	phosphorylation	up-regulates activity	0.2	Mass spectrometry identified four serine residues of G6PD phosphorylated by NIK (Extended Data Fig. 8f). All of these serines, except S278, are conserved between human and mouse G6PD proteins. In transfected cells, NIK stimulated G6PD activity, which was not affected by S8A or S486A mutation but abolished by S40A mutation (Extended Data Fig. 8g).	SIGNOR-277545
Q8TD19	Q8NHV4	1	phosphorylation	up-regulates activity	0.426	Nek9 phosphorylates NEDD1 on Ser377 driving its recruitment and thereby that of γ-tubulin to the centrosome in mitotic cells.	SIGNOR-263016
O75604	P37173	0	phosphorylation	up-regulates activity	0.2	Here, we report the role of USP2a in promoting metastasis by facilitating TGF-β-triggered signaling. USP2a interacts with TGFBR1 and TGFBR2 upon TGF-β stimulation and removes K33-linked polyubiquitin chains from Lys502 of TGFBR1, promoting the recruitment of SMAD2/3. Simultaneously, TGFBR2 phosphorylates Ser207/Ser225 of USP2a, leading to the disassociation of SMAD2/3 from TGFBR1.	SIGNOR-273604
Q13387	P45984	2	binding	up-regulates	0.571	These experiments demonstrated that 10 different jnk isoforms bound to both jip proteins.	SIGNOR-70866
Q96EB6	P24941	0	phosphorylation	up-regulates activity	0.465	Sirt1 is in turn phosphorylated by Cdk2, which may further regulate its activity.\|Taken together, these data demonstrate that Cdk2 deletion does not decrease Hif1\u03b1 expression induced by HX, and strongly suggests that the phosphorylation of Sirt1 at Ser47 by Cdk2 requires Sirt1 deacetylase activity.	SIGNOR-279513
Q15672	Q16539	0	phosphorylation	up-regulates	0.269	Phosphorylation of serine 68 of twist1 by mapks stabilizes twist1 protein and promotes breast cancer cell invasiveness. this ser 68 is phosphorylated by p38, c-jun n-terminal kinases (jnk), and extracellular signal-regulated kinases1/2 in vitro	SIGNOR-173409
Q13546	Q8N5C8	2	binding	up-regulates activity	0.574	Tab2 and tab3 activate the jun n-terminal kinase and nuclear factor-kappab pathways through the specific recognition of lys 63-linked polyubiquitin chains by its npl4 zinc-finger (nzf) domain.	SIGNOR-161787
P55072	O00124	0	relocalization	down-regulates quantity	0.521	The human protein named Rep8 or Ubxd6 as a new cofactor of p97. Rep8 tethers p97 to the ER membrane for efficient ER-associated degradation.	SIGNOR-261002
Q9BV68	Q16595	1	ubiquitination	down-regulates quantity by destabilization	0.385	Depletion of RNF126 by specific small interfering RNA delays the degradation of frataxin precursor and increases its stability.\|Here we report on the identification of really interesting new gene finger protein 126 (RNF126) as the E3 ligase that ubiquitinates frataxin.	SIGNOR-278663
Q99731	P32248	2	binding	up-regulates activity	0.784	CCL19 and CCL21 are endogenous agonists for the seven-trans membrane receptor CCR7.	SIGNOR-278123
Q5TCX8	O15111	1	phosphorylation	down-regulates activity	0.2	Immunoprecipitation and in vitro kinase analysis revealed that MLK4 physically interacts with both IKKalpha and beta, but preferentially phosphorylates IKKalpha over IKKbeta (XREF_FIG	SIGNOR-279067
O43541	P84022	2	binding	down-regulates activity	0.497	Smad6 and smad7, can prevent tgfb signaling by interacting either with the receptor or with smad2 and smad3	SIGNOR-64071
O95372	P17677	1	deacetylation	down-regulates quantity by destabilization	0.477	Acyl-protein thioesterase 2 catalyzes the deacylation of peripheral membrane-associated GAP-43. In this work, we investigated the deacylation of growth-associated protein-43 (GAP-43), a dually acylated protein at cysteine residues 3 and 4. Thus, the results demonstrate that APT-2 is the protein thioesterase involved in the acylation/deacylation cycle operating in GAP-43 subcellular distribution.we demonstrated that the reduction in the protein level was abrogated when cells were also treated with proteasome inhibitors (chloroquine, MG132 and lactacystin) which strongly suggest that GAP-43 deacylation is an early and necessary step for its later ubiquitination and degradation by the proteasome. In addition, it also suggests that acyl-protein thioesterase levels not only regulate palmitate turnover but also global protein turnover of GAP-43.	SIGNOR-266768
P60484	P37231	0	null	down-regulates activity	0.456	The PAX8-PPARγ rearrangement leads to strong induction of the PPARγ protein and the consequent abrogation of the normal PPARγ function. PPARγ overexpression abolishes the PTEN-inhibitory effect on immunoactive AKT, which in turn induces the PI3K signaling pathway.	SIGNOR-251997
Q15772	Q92736	1	phosphorylation	down-regulates activity	0.248	Conclusions : Unlike other kinases (PKA, CaMKII) that increase RyR2 activity, SPEG phosphorylation reduces RyR2 mediated SR Ca 2+ -release.\|Further, we show that SPEG phosphorylates RyR2 at a previously uncharacterized serine (S2367) located in the central domain of the channel. xref Importantly, in contrast to previously studied phosphorylation sites that activate RyR2 (e.g. S2808, S2814), we show that SPEG mediated RyR2-S2367 phosphorylation suppresses pathogenic diastolic SR Ca 2+ -leak.	SIGNOR-279114
Q7Z6I6	P60953	1	gtpase-activating protein	down-regulates activity	0.458	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-260487
P51587	P53350	0	phosphorylation	down-regulates activity	0.539	M phase-specific phosphorylation of brca2 by polo-like kinase 1 correlates with the dissociation of the brca2-p/caf complex.Plk1 interacts with brca2 in vivo, and mutation of ser193, ser205/206, and thr203/207 to ala in br-n1 abolished plk1 phosphorylation, suggesting that brca2 is the substrate of plk1	SIGNOR-102486
Q02127	P01106	0	transcriptional regulation	up-regulates quantity by expression	0.346	PPAT, catalyzing the first step of purine synthesis, and DHODH, an enzyme generating uridine in the middle of the pyrimidine synthesis pathway, were validated as direct c-MYC target genes by all criteria.	SIGNOR-267382
P27361	Q9NQ66	1	phosphorylation	up-regulates activity	0.412	Plc beta1 could be efficiently phosphorylated by activated mitogen-activated protein kinase but not by pka. The erk phosphorylation site was mapped to serine 982	SIGNOR-106565
Q86WV6	Q9UJV9	2	binding	up-regulates activity	0.2	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-266403
P07492	P30550	2	binding	up-regulates	0.784	Indeed, many potent mitogens such as thrombin, lysophosphatidic acid (lpa), gastrin-releasing peptide (grp), endothelin and prostaglandins stimulate cell proliferation by acting on their cognate gpcrs in various cell types.	SIGNOR-152676
Q9UHW9	Q9UEW8	0	phosphorylation	down-regulates activity	0.569	We observed that in vitro activated STE20/SPS1-related proline/alanine-rich kinase (SPAK) complexed to its regulatory MO25 subunit phosphorylated KCC3 at Ser-96 and that in Xenopus laevis oocytes Ser-96 of human KCC3 is phosphorylated in isotonic conditions and becomes dephosphorylated during incubation in hypotonicity, leading to a dramatic increase in KCC3 function.	SIGNOR-276597
Q9NZJ5	Q08209	1	phosphorylation	down-regulates activity	0.2	CN becomes phosphorylated by PERK, decreasing its activity.\|Finally, evidence is presented that PERK phosphorylates CN-A at low resting levels of Ca 2+.	SIGNOR-278933
P06241	P51911	1	phosphorylation	down-regulates activity	0.333	We identify, for the first time, tyrosine-phosphorylated calponin h3 within COS 7 cells, before and after their transfection with the pSV vector containing cDNA encoding the cytoplasmic, Src-related, tyrosine kinase, Fyn. we have localized the tyrosines phosphorylated without actin to Tyr261 in calponin h3 and to Tyr261 and Tyr182 in calponin h1. Tyrosine phosphorylation of calponins inhibits their binding to F-actin	SIGNOR-251157
A0A1B0GVQ0	Q00535	0	phosphorylation	down-regulates quantity by destabilization	0.2	Cdk5 also phosphorylates PSD-95-interacting protein Spine Associated RapGAP (SPAR), resulting in its degradation ([98], Table 2).	SIGNOR-280219
O00470	P35453	2	binding	up-regulates activity	0.499	We now show that the Hoxa-9 protein physically interacts with Meis1 proteins. Hox proteins from the other AbdB-like paralogs, Hoxa-10, Hoxa-11, Hoxd-12, and Hoxb-13, also form DNA binding complexes with Meis1b. DNA binding complexes formed by Meis1 with Hox proteins dissociate much more slowly than DNA complexes with Meis1 alone, suggesting that Hox proteins stabilize the interactions of Meis1 proteins with their DNA targets.	SIGNOR-241235
P12931	Q16827	0	dephosphorylation	down-regulates activity	0.422	SRC activation triggered by loss of PTPRO leads to c-CBL degradation.\|These data corroborate that PTPRO directly dephosphorylates SRC at Y416.	SIGNOR-277004
P10911	P60953	1	guanine nucleotide exchange factor	up-regulates activity	0.777	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-260558
P08047	O43186	2	binding	up-regulates activity	0.324	Zinc finger DNA-binding domains of both Sp1 and Sp3 interact with Crx. Sp4 and Sp1 produce much higher levels of transcriptional activation when co-transfected with Crx, they may additionally act by directly increasing the rate of transcriptional initiation by the general transcriptional apparatus through their activation domains.	SIGNOR-225336
P41221	Q12857	0	transcriptional regulation	down-regulates quantity	0.2	By integrating transcriptomic profiling (RNA-seq) of Nfia- and Nfix-deficient GNPs with epigenomic profiling (ChIP-seq against NFIA, NFIB and NFIX, and DNase I hypersensitivity assays), we reveal that these transcription factors share a large set of potential transcriptional targets, suggestive of complementary roles for these NFI family members in promoting neural development	SIGNOR-268877
O15530	Q05655	1	phosphorylation	up-regulates activity	0.577	PDK1 phosphorylated the activation loop sites of PKCzeta and PKCdelta in vitro and in a phosphoinositide 3-kinase (PI 3-kinase)-dependent manner in vivo in human embryonic kidney (293) cells. PKCδ was also phosphorylated in the activation loop site (T505)	SIGNOR-250269
Q00535	P04626	1	phosphorylation	up-regulates activity	0.274	Since Tyr-654 is the ERBB2 phosphorylation site on beta-catenin, this result is consistent with our hypothesis that CDK5 activates ERBB2 , which in turn phosphorylates beta-catenin on Tyr-654, leading to a shift of beta-catenin away from the adherens junction and into the nucleus where it can serve as a transcriptional co-activator.\|Taken together with the results of our kinase analysis, these observations suggest that CDK5 phosphorylation of both ERBB2 and ERBB3 and AR could drive a feedback loop, in which ERBB2 and ERBB3 promotes beta-catenin transcriptional activity that then contributes to higher expression of ERBB3.	SIGNOR-279155
P53355	P53355	2	phosphorylation	down-regulates activity	0.2	The pro-apoptotic function of death-associated protein kinase is controlled by a unique inhibitory autophosphorylation-based mechanism.These results are consistent with a molecular model in which phosphorylation on ser(308) stabilizes a locked conformation of the cam-regulatory domain within the catalytic cleft and simultaneously also interferes with cam binding.	SIGNOR-110807
P24928	P28482	0	phosphorylation	down-regulates	0.311	Erk1/2 are major ser-5 kinases after h2o2 treatment. These results suggest that subsequent to h2o2 treatment, the ser-5-phosphorylated form, but not the ser-2-phosphorylated form or the unphosphorylated form, is targeted for rapid proteasomal degradation through its ubiquitination.	SIGNOR-120160
P48431	P24941	0	phosphorylation	up-regulates activity	0.394	Cdk2 physically interacts with Sox2 and phosphorylates Sox2 at Ser 39 and Ser 253 in vitro.	SIGNOR-279448
O43193	Q03113	2	binding	up-regulates activity	0.25	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-257222
Q12982	P60953	2	binding	up-regulates activity	0.709	Cdo-bnip-2-cdc42 complex stimulates cdc42 activation which in turn promotes p38 alpha/beta activity and cell differentiation.	SIGNOR-179861
P63092	P35367	2	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-256778
P36406	O14920	0	phosphorylation	down-regulates activity	0.287	Phosphorylation of ARD1 by IKKbeta reduced its growth suppression effect.	SIGNOR-279337
Q9Y2H1	Q9Y2H1	2	phosphorylation	up-regulates	0.2	Ndr1/ndr2 protein kinase is activated by phosphorylation on the activation loop phosphorylation site ser281/ser282 and the hydrophobic motif phosphorylation site thr444/thr442. Autophosphorylation of ndr is responsible for phosphorylation on ser281/ser282, whereas thr444/thr442 is targeted by an upstream kinase. Here we show that mst3, a mammalian ste20-like protein kinase, is able to phosphorylate ndr protein kinase at thr444/thr442. In vitro, mst3 selectively phosphorylated thr442 of ndr2, resulting in a 10-fold stimulation of ndr activity.	SIGNOR-142518
O95837	Q96LB1	2	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-257434
Q13315	Q8WYQ5	1	phosphorylation	up-regulates quantity by stabilization	0.27	Specifically, radiation-induced ATM-dependent phosphorylation of DGCR8 at serine 677 facilitates USP51 to bind, deubiquitinate, and stabilize DGCR8, which leads to the recruitment of DGCR8 and DGCR8's binding partner RNF168 to MDC1 and RNF8 at DSBs.	SIGNOR-277307
Q5VWQ8	P40763	2	binding	down-regulates activity	0.346	DAB2IP could interact with the signal transducer and activator of transcription 3 (STAT3) via its unique PR domain and suppress STAT3 phosphorylation and transactivation, leading to the inhibition of survivin expression in PCa cells.	SIGNOR-254761
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
P35368	P17252	0	phosphorylation	down-regulates activity	0.39	Phorbol ester-induced phosphorylation of the Ser394 and Ser400 as well as GRK2-mediated phosphorylation of the Ser404, Ser408, and Ser410, resulted in the desensitization of alpha1BAR-mediated inositol phosphate response.	SIGNOR-248988
Q6ZWJ1	Q12846	2	binding	up-regulates activity	0.799	Akt2 phosphorylates Synip to regulate docking and fusion of GLUT4-containing vesicles. These data demonstrate that insulin activation of Akt2 specifically regulates the docking/fusion step of GLUT4-containing vesicles at the plasma membrane through the regulation of Synip phosphorylation and Synip-Syntaxin4 interaction.Thus, our data demonstrate that insulin-stimulated Akt2-dependent phosphorylation of Synip on serine residue 99 results in reduced binding interactions between Synip and Syntaxin4.	SIGNOR-262634
Q9HB89	O95837	2	binding	up-regulates activity	0.435	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-256894
Q99835	Q2M1P5	1	relocalization	up-regulates activity	0.632	Here, we demonstrate that Kif7, a mammalian homologue of Drosophila Costal2 (Cos2), is a cilia-associated protein that regulates signaling from the membrane protein Smoothened (Smo) to Gli transcription factorsIn response to activation of Smo Kif7 at the cilia tip may antagonize Sufu to promote activation of Gli proteins.	SIGNOR-209605
Q13164	Q06413	1	phosphorylation	up-regulates	0.766	Bmk1 dramatically enhances the transactivation activity of mef2c by phosphorylating a serine residue at amino acid position 387 in this transcription factor.	SIGNOR-53545
Q9BYF1	P01019-PRO_0000420660	1	cleavage	up-regulates quantity	0.2	At first, ACE2 has been demonstrated to induce conversion of Ang I into Ang (1–7) by means of intermediate production of Ang (1–9), a fragment with unknown function.	SIGNOR-260227
P30559	P63096	2	binding	up-regulates activity	0.449	OT binds to its cognate G protein–coupled receptor (OTR) and exerts diverse effects, including stimulation (Gs) or inhibition (Gi/o) of adenylyl cyclase, stimulation of potassium channel currents (Gi), and activation of phospholipase C (Gq).	SIGNOR-270330
P04049	P12931	0	phosphorylation	up-regulates	0.605	We also show that phosphorylation of raf-1 on serine 338 by pak1 and tyrosines 340 and 341 by src relieves autoinhibition and that this occurs through a specific decrease in the binding of the raf-1 regulatory domain to its catalytic domain.	SIGNOR-97639
P15036	P02818	1	transcriptional regulation	up-regulates quantity by expression	0.2	Ets2 is expressed at high levels during the differentiation and matrix mineralization phases of MC3T3-E1 culture. In addition, several extracellular matrix (ECM) associated gene products are targets of Ets2. Some of these matrix associated genes include: bone sialoprotein, osteonectin, osteocalcin and osteopontin	SIGNOR-259875
Q14527	Q96EP1	0	polyubiquitination	down-regulates quantity by destabilization	0.482	CHFR functions as a ubiquitin ligase for HLTF to regulate its stability and functions. CHFR negatively regulates and ubiquitinates HLTF. Taken together, this is the first report identifying the regulatory mechanism of HLTF by CHFR, suggesting that CHFR-mediated downregulation of HLTF may help protect against cancer.	SIGNOR-271460
Q2M1P5	P10071	2	binding	up-regulates quantity by stabilization	0.577	These results suggest a role for Kif7 in coordinating Hh signal transduction at the tip of cilia and preventing Gli3 cleavage into a repressor form in the presence of Hh.	SIGNOR-209614
P13611	P04637	0	transcriptional regulation	up-regulates quantity by expression	0.29	By using in vitro and in vivo assays, we showed CSPG2 to be directly transactivated by p53.	SIGNOR-255441
Q00535	P29474	1	phosphorylation	down-regulates	0.371	Together, our data suggest that cdk5 can phosphorylate enos at the ser-113 site and down-regulate enos-derived no levels.	SIGNOR-164080
Q8NFZ4	Q86UL8	2	binding	up-regulates activity	0.403	S-SCAM is a member of the membrane-associated guanylate kinase (MAGUK) family of PDZ-domain-containing proteins that include the synaptic organising molecule PSD-95. The PDZ domain of S-SCAM binds to the C-terminal tail of NL2, forming a ternary complex at the cell membrane (Figure 2b). The DGC is potentially recruited to the postsynaptic membrane though a direct neurexin–dystroglycan interaction and an indirect interaction with NL2 via the synaptic scaffolding protein S-SCAM.	SIGNOR-265444
P56945	Q13882	0	phosphorylation	up-regulates	0.599	Protein-tyrosine kinase 6 promotes peripheral adhesion complex formation and cell migration by phosphorylating p130 crk-associated substrate. Tyrosine residues 165 and 664 of p130cas were both phosphorylated by ptk6 in vitro	SIGNOR-177242
P17612	P21333	1	phosphorylation	up-regulates	0.2	Site-directed mutagenesis analysis indicated that serine 2152 is the unique substrate in the c-terminal region of abp for endogenously activated pka.	SIGNOR-126659
P31749	P84022	2	binding	down-regulates	0.622	Pkb inhibits smad3 by preventing its phosphorylation, binding to smad4 and nuclear translocation. [...] Regulation of smad3 by pkb occurs through a kinase-activity-independent mechanism, resulting in a decrease in smad3-mediated transcription and protection of cells against tgf-beta-induced apoptosis.	SIGNOR-123606

Q8IWS0

P17480

2

binding

down-regulates

0.28

We demonstrate that phf6 is a nucleolus, ribosomal rna promoter-associated protein. Phf6 directly interacts with upstream binding factor (ubf) through its phd1 domain and suppresses ribosomal rna (rrna) transcription by affecting the protein level of ubf

SIGNOR-200133

P35968

P23470

0

dephosphorylation

down-regulates activity

0.253

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

SIGNOR-254707

P41440

P17676

0

transcriptional regulation

up-regulates quantity by expression

0.2

Collectively, these results identify transcriptionally important regions in the hRFC-C minimal promoter that include a GC-box and CCAAT-box, and suggest that cooperative interactions between Sp1 and C/EBP beta are essential for hRFC-C transactivation.

SIGNOR-254053

Q13351

P42773

1

transcriptional regulation

up-regulates quantity by expression

0.266

Thus, EKLF is a direct regulator of p18INK4c gene expression, and much of EKLF's role in driving erythroid cell differentiation may occur via p18INK4c.

SIGNOR-266046

O43683

Q9Y6D9

1

relocalization

up-regulates activity

0.727

Spindle checkpoint protein Bub1 is required for kinetochore localization of Mad1, Mad2, Bub3, and CENP-E, independently of its kinase activity

SIGNOR-252017

Q15762

Q92692

2

binding

up-regulates activity

0.2

CD226 (DNAM-1) is an adhesion molecule involved in NK and T cell-mediated cytotoxicity against certain tumors. Here, we have identified the human poliovirus receptor-related (PRR) family members CD155 [poliovirus receptor (PVR)] and CD112 (nectin-2/PRR-2) as the ligands for human CD226.

SIGNOR-261426

P42127

P41968

2

binding

down-regulates activity

0.511

The melanocortin (MC) receptor family consists of five Gs-coupled receptors that control various physiological functions in response to four distinct agonists, adrenocorticotropic hormone (ACTH, also known as corticotrophin) and alpha, beta, and gamma melanocyte-stimulating hormone (MSH), which are derived from the proopiomelanocortin precursor protein, and two inverse agonists, agouti and agouti-related proteins

SIGNOR-268703

P78317

P29590

1

polyubiquitination

down-regulates quantity by destabilization

0.487

Upon TGF-β induction, interaction of Arkadia with phosphorylated Smad2 triggers degradation of SnoN, whereas upon arsenic treatment, interaction of Arkadia with poly-SUMO in PML nuclear bodies induces degradation of polysumoylated PML together with RNF4.

SIGNOR-272884

P42338

P01111

2

binding

up-regulates

0.668

Grb2 binds and activates sos, which then activates ras, and this activates p110 independently of p85./it was also described that ras interacts with pi3k in a direct manner./lysine residue 227 is essential for the interaction of ras with pi3k

SIGNOR-175225

P35442

Q08722

2

binding

up-regulates

0.592

We report here that iap is a receptor for the ts1 cbd and its vvm-containing peptides and that a function-blocking anti-iap mab inhibits the chemotactic response to ts1 and its cbd peptides in endothelial cells.

SIGNOR-39749

Q17RY0

P28482

0

phosphorylation

up-regulates activity

0.325

Our results indicate that CPEB4 activation is driven by ERK2- and Cdk1 mediated hyperphosphorylation of at least 12 residues in the intrinsically disordered NTD.|We concluded that, in interphase, unphosphorylated CPEB4 phase separates into liquid like droplets that recruit mRNAs but are inactive for cytoplasmic polyadenylation and translation, whereas in M-phase, CPEB4 is phosphorylated by ERK2 and Cdk1 and recovers its monomeric form, which can drive the cytoplasmic polyadenylation of target mRNAs.

SIGNOR-280021

Q9UQ26

O14795

1

relocalization

up-regulates activity

0.358

N-terminal interactions of RIMs with RAB3 and MUNC13 regulate DCV fusion. Through N-terminal interactions, RIMs position MUNC13 and recruit DCVs via RAB3, which is located on the vesicle

SIGNOR-264383

P49841

Q9NZQ7

1

phosphorylation

down-regulates quantity by destabilization

0.307

We show that glycogen synthase kinase 3β (GSK3β) interacts with PD-L1 and induces phosphorylation-dependent proteasome degradation of PD-L1 by β-TrCP.

SIGNOR-277275

Q92918

P07948

0

phosphorylation

up-regulates activity

0.381

BCR ligation induced rapid tyrosine-phosphorylation of HPK1 mainly by Syk and Lyn, resulting in its association with BASH and catalytic activation. Tyr-379 within HPK1 is essential for binding to BASH and thus strongly suggest that the DDDYDDV sequence containing the phosphorylated Tyr-379 is the binding site for the BASH SH2 domain.

SIGNOR-251403

Q16539

P52564

0

phosphorylation

up-regulates activity

0.744

These data indicate that mkk6 phosphorylates p38 map kinase on thr-180 and tyr-182, the sites of phosphorylation that activate p38 map kinase

SIGNOR-40427

P35354

O95644

0

transcriptional regulation

up-regulates quantity by expression

0.316

NFAT induces the transcription of the COX2 (cyclo-oxygenase-2) gene incancer cells thereby enhancing invasive migration

SIGNOR-264026

P46020

P17612

0

phosphorylation

up-regulates activity

0.432

Phosphorylation of the alpha and beta subunits by the 3',5'-cyclic adenosine monophosphate (cAMP)-dependent protein kinase (PKA) also relieves inhibition of the gamma subunit and thereby activates the enzyme.

SIGNOR-267411

P01106

P11166

1

transcriptional regulation

up-regulates quantity

0.43

C-Myc directly transactivates genes encoding GLUT1, phosphofructokinase, and enolase and increases glucose uptake in Rat1 fibroblasts. Nuclear run-on studies confirmed that the GLUT1 transcriptional rate is elevated by c-Myc. Our findings suggest that overexpression of the c-Myc oncoprotein deregulates glycolysis through the activation of several components of the glucose metabolic pathway.

SIGNOR-259987

Q00987

Q9H0A0

0

ubiquitination

down-regulates quantity by destabilization

0.33

NAT10 acetylates p53 at K120 and stabilizes p53 by counteracting Mdm2 action. In addition, NAT10 promotes Mdm2 degradation with its intrinsic E3 ligase activity.

SIGNOR-272405

P30793

O95433

2

binding

up-regulates activity

0.297

The interaction of GCH1 with Aha1 may recruit GCH1 into the eNOS/Hsp90 complex so as to support local changes in nitric oxide production by endothelial cells.

SIGNOR-252213

P36956

P14618

1

transcriptional regulation

up-regulates quantity by expression

0.29

Well-described targets of srebp-1 and the carbohydrate response element binding protein (chrebp), which include the following: fatty acid synthase (fas), acetyl coa carboxylase (acc1), and liver pyruvate kinase (l-pk)

SIGNOR-166381

P16949

Q9UQM7

0

phosphorylation

down-regulates

0.403

Involved in the regulation of the microtubule (mt) filament system by destabilizing microtubules. Prevents assembly and promotes disassembly of microtubules. In vitro, ser16 of recombinant human stathmin was phosphorylated also by purified cam kinase ii, and in vivo, cam kinase ii activity was indeed stimulated in cd2-triggered jurkat cells. Altogether, our results favor an association of cam kinase ii activity with costimulatory signals of t lymphocyte activation and phosphorylation of stathmin on ser16.

SIGNOR-149640

Q16288

P19174

2

binding

up-regulates

0.619

Unglycosylated trka core protein is phosphorylated even in the absence of ligand stimulation and displays constitutive kinase activity as well as constitutive interaction with the signaling molecules shc and plc-gamma.

SIGNOR-67404

Q9BXW9

O14757

0

phosphorylation

up-regulates activity

0.585

In vitro and in vivo experiments show that phosphorylation of s331 is mediated by chk1, the s-phase checkpoint kinase implicated in the fanconi anemia dna repair pathway. phosphorylation at this site is dependent on chk1, signifying the importance of the s-phase checkpoint in the activation of fanconi anemia pathway.

SIGNOR-107042

P17252

P04049

1

phosphorylation

down-regulates

0.558

Pka can inhibit raf-1 function directly via phosphorylation of the raf-1 kinase domain

SIGNOR-34761

P46937

Q15208

0

phosphorylation

down-regulates activity

0.383

We show that mammalian NDR1/2 kinases phosphorylate YAP1 on S127 and thereby negatively regulate YAP1 activity in tissue-cultured cells.

SIGNOR-259855

P48730

P11308

1

phosphorylation

down-regulates activity

0.2

Interestingly, only CKId, but not other CKI isoforms or CKII could promote ERG degradation under ectopic expression conditions (XREF_FIG).|These results indicate that phosphorylation of ERG by CKIdelta within the SPOP-recognition degron triggers its interaction with SPOP to promote ERG destruction .

SIGNOR-280234

Q04206

Q99576

2

binding

down-regulates activity

0.373

GILZ inhibits NF-kappaB nuclear translocation and DNA binding due to a direct protein-to-protein interaction of GILZ with the NF-kappaB subunits.

SIGNOR-253297

P06850

P10275

0

transcriptional regulation

down-regulates quantity by repression

0.305

A direct androgenic involvement in the expression of human corticotropin-releasing hormone|A potential androgen-responsive element (ARE) in the human CRH promoter was subsequently analyzed with bandshifts and cotransfections in neuroblastoma cells. In the presence of testosterone, recombinant human AR bound specifically to the CRH-ARE.

SIGNOR-268723

O43521

Q16611

2

binding

up-regulates

0.837

Bim, and puma bind with high affinity to all pro-survival proteins

SIGNOR-196932

O95644

P35354

1

transcriptional regulation

up-regulates quantity by expression

0.316

NFAT induces the transcription of the COX2 (cyclo-oxygenase-2) gene incancer cells thereby enhancing invasive migration

SIGNOR-264026

P31751

P49840

1

phosphorylation

down-regulates

0.557

Activated pi3k/akt pathway results in inhibitory phosphorylation of gsk3

SIGNOR-138179

P53355

P19105

1

phosphorylation

up-regulates activity

0.275

DAPK Phosphorylates Myosin II RLC in Vitro and in Vivo. Together these results show that similar to the conventional MLCKs, Ser-19 is the primary RLC residue phosphorylated by DAPK and that phosphorylation of Thr-18 is also possible.

SIGNOR-262842

Q8TB45

Q15418

0

phosphorylation

down-regulates

0.492

We found that deptor was rapidly phosphorylated on three serines in a conserved degron, facilitating binding and ubiquitylation by the f box protein _trcp, with consequent proteasomal degradation of deptor. Phosphorylation of the _trcp degron in deptor is executed by ck1

SIGNOR-176883

Q99880

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-265389

Q7KZF4

P42226

2

binding

up-regulates activity

0.479

STAT6 interacted with p100 in vitro and in vivo. Here, we show that the TAD of STAT6 is interacting with p100. p100 was found to enhance the STAT6-mediated transcription [.].

SIGNOR-259134

Q9H4G4

P51617

0

phosphorylation

up-regulates activity

0.325

We found that TIRAP-MyD88 dependent kinase IRAK1 phosphorylated GAPR-1 at Serine 58 site. The phosphorylation of GAPR-1 promoted its interaction with TRAM-TRIF dependent inhibitor TMED7, and impaired TMED7-mediated disruption of the TRAM-TRIF complex to trigger IFN-β and the IL10 secretion.

SIGNOR-262887

Q9UKT5

P49841

0

phosphorylation

up-regulates

0.2

Gsk3beta-mediated phosphorylation of fbx4 ser12 during the g1/s transition regulates fbx4 dimerization, which in turn governs fbx4-driven e3 ligase activity.

SIGNOR-171648

P02671

P50281

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-14 27YVATRDN g-chain| 105XDAATLKSR g-chain | 92LTYNPDES g-chain |105LTTNIXEXL a-chain|433LVTSKGDKE a-chain| 117FXSANNRD a-chain

SIGNOR-263620

Q99558

P11413

1

phosphorylation

up-regulates activity

0.2

Mass spectrometry identified four serine residues of G6PD phosphorylated by NIK (Extended Data Fig. 8f). All of these serines, except S278, are conserved between human and mouse G6PD proteins. In transfected cells, NIK stimulated G6PD activity, which was not affected by S8A or S486A mutation but abolished by S40A mutation (Extended Data Fig. 8g).

SIGNOR-277545

Q8TD19

Q8NHV4

1

phosphorylation

up-regulates activity

0.426

Nek9 phosphorylates NEDD1 on Ser377 driving its recruitment and thereby that of γ-tubulin to the centrosome in mitotic cells.

SIGNOR-263016

O75604

P37173

0

phosphorylation

up-regulates activity

0.2

Here, we report the role of USP2a in promoting metastasis by facilitating TGF-β-triggered signaling. USP2a interacts with TGFBR1 and TGFBR2 upon TGF-β stimulation and removes K33-linked polyubiquitin chains from Lys502 of TGFBR1, promoting the recruitment of SMAD2/3. Simultaneously, TGFBR2 phosphorylates Ser207/Ser225 of USP2a, leading to the disassociation of SMAD2/3 from TGFBR1.

SIGNOR-273604

Q13387

P45984

2

binding

up-regulates

0.571

These experiments demonstrated that 10 different jnk isoforms bound to both jip proteins.

SIGNOR-70866

Q96EB6

P24941

0

phosphorylation

up-regulates activity

0.465

Sirt1 is in turn phosphorylated by Cdk2, which may further regulate its activity.|Taken together, these data demonstrate that Cdk2 deletion does not decrease Hif1\u03b1 expression induced by HX, and strongly suggests that the phosphorylation of Sirt1 at Ser47 by Cdk2 requires Sirt1 deacetylase activity.

SIGNOR-279513

Q15672

Q16539

0

phosphorylation

up-regulates

0.269

Phosphorylation of serine 68 of twist1 by mapks stabilizes twist1 protein and promotes breast cancer cell invasiveness. this ser 68 is phosphorylated by p38, c-jun n-terminal kinases (jnk), and extracellular signal-regulated kinases1/2 in vitro

SIGNOR-173409

Q13546

Q8N5C8

2

binding

up-regulates activity

0.574

Tab2 and tab3 activate the jun n-terminal kinase and nuclear factor-kappab pathways through the specific recognition of lys 63-linked polyubiquitin chains by its npl4 zinc-finger (nzf) domain.

SIGNOR-161787

P55072

O00124

0

relocalization

down-regulates quantity

0.521

The human protein named Rep8 or Ubxd6 as a new cofactor of p97. Rep8 tethers p97 to the ER membrane for efficient ER-associated degradation.

SIGNOR-261002

Q9BV68

Q16595

1

ubiquitination

down-regulates quantity by destabilization

0.385

Depletion of RNF126 by specific small interfering RNA delays the degradation of frataxin precursor and increases its stability.|Here we report on the identification of really interesting new gene finger protein 126 (RNF126) as the E3 ligase that ubiquitinates frataxin.

SIGNOR-278663

Q99731

P32248

2

binding

up-regulates activity

0.784

CCL19 and CCL21 are endogenous agonists for the seven-trans membrane receptor CCR7.

SIGNOR-278123

Q5TCX8

O15111

1

phosphorylation

down-regulates activity

0.2

Immunoprecipitation and in vitro kinase analysis revealed that MLK4 physically interacts with both IKKalpha and beta, but preferentially phosphorylates IKKalpha over IKKbeta (XREF_FIG

SIGNOR-279067

O43541

P84022

2

binding

down-regulates activity

0.497

Smad6 and smad7, can prevent tgfb signaling by interacting either with the receptor or with smad2 and smad3

SIGNOR-64071

O95372

P17677

1

deacetylation

down-regulates quantity by destabilization

0.477

Acyl-protein thioesterase 2 catalyzes the deacylation of peripheral membrane-associated GAP-43. In this work, we investigated the deacylation of growth-associated protein-43 (GAP-43), a dually acylated protein at cysteine residues 3 and 4. Thus, the results demonstrate that APT-2 is the protein thioesterase involved in the acylation/deacylation cycle operating in GAP-43 subcellular distribution.we demonstrated that the reduction in the protein level was abrogated when cells were also treated with proteasome inhibitors (chloroquine, MG132 and lactacystin) which strongly suggest that GAP-43 deacylation is an early and necessary step for its later ubiquitination and degradation by the proteasome. In addition, it also suggests that acyl-protein thioesterase levels not only regulate palmitate turnover but also global protein turnover of GAP-43.

SIGNOR-266768

P60484

P37231

0

null

down-regulates activity

0.456

The PAX8-PPARγ rearrangement leads to strong induction of the PPARγ protein and the consequent abrogation of the normal PPARγ function. PPARγ overexpression abolishes the PTEN-inhibitory effect on immunoactive AKT, which in turn induces the PI3K signaling pathway.

SIGNOR-251997

Q15772

Q92736

1

phosphorylation

down-regulates activity

0.248

Conclusions : Unlike other kinases (PKA, CaMKII) that increase RyR2 activity, SPEG phosphorylation reduces RyR2 mediated SR Ca 2+ -release.|Further, we show that SPEG phosphorylates RyR2 at a previously uncharacterized serine (S2367) located in the central domain of the channel. xref Importantly, in contrast to previously studied phosphorylation sites that activate RyR2 (e.g. S2808, S2814), we show that SPEG mediated RyR2-S2367 phosphorylation suppresses pathogenic diastolic SR Ca 2+ -leak.

SIGNOR-279114

Q7Z6I6

P60953

1

gtpase-activating protein

down-regulates activity

0.458

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-260487

P51587

P53350

0

phosphorylation

down-regulates activity

0.539

M phase-specific phosphorylation of brca2 by polo-like kinase 1 correlates with the dissociation of the brca2-p/caf complex.Plk1 interacts with brca2 in vivo, and mutation of ser193, ser205/206, and thr203/207 to ala in br-n1 abolished plk1 phosphorylation, suggesting that brca2 is the substrate of plk1

SIGNOR-102486

Q02127

P01106

0

transcriptional regulation

up-regulates quantity by expression

0.346

PPAT, catalyzing the first step of purine synthesis, and DHODH, an enzyme generating uridine in the middle of the pyrimidine synthesis pathway, were validated as direct c-MYC target genes by all criteria.

SIGNOR-267382

P27361

Q9NQ66

1

phosphorylation

up-regulates activity

0.412

Plc beta1 could be efficiently phosphorylated by activated mitogen-activated protein kinase but not by pka. The erk phosphorylation site was mapped to serine 982

SIGNOR-106565

Q86WV6

Q9UJV9

2

binding

up-regulates activity

0.2

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-266403

P07492

P30550

2

binding

up-regulates

0.784

Indeed, many potent mitogens such as thrombin, lysophosphatidic acid (lpa), gastrin-releasing peptide (grp), endothelin and prostaglandins stimulate cell proliferation by acting on their cognate gpcrs in various cell types.

SIGNOR-152676

Q9UHW9

Q9UEW8

0

phosphorylation

down-regulates activity

0.569

We observed that in vitro activated STE20/SPS1-related proline/alanine-rich kinase (SPAK) complexed to its regulatory MO25 subunit phosphorylated KCC3 at Ser-96 and that in Xenopus laevis oocytes Ser-96 of human KCC3 is phosphorylated in isotonic conditions and becomes dephosphorylated during incubation in hypotonicity, leading to a dramatic increase in KCC3 function.

SIGNOR-276597

Q9NZJ5

Q08209

1

phosphorylation

down-regulates activity

0.2

CN becomes phosphorylated by PERK, decreasing its activity.|Finally, evidence is presented that PERK phosphorylates CN-A at low resting levels of Ca 2+.

SIGNOR-278933

P06241

P51911

1

phosphorylation

down-regulates activity

0.333

We identify, for the first time, tyrosine-phosphorylated calponin h3 within COS 7 cells, before and after their transfection with the pSV vector containing cDNA encoding the cytoplasmic, Src-related, tyrosine kinase, Fyn. we have localized the tyrosines phosphorylated without actin to Tyr261 in calponin h3 and to Tyr261 and Tyr182 in calponin h1. Tyrosine phosphorylation of calponins inhibits their binding to F-actin

SIGNOR-251157

A0A1B0GVQ0

Q00535

0

phosphorylation

down-regulates quantity by destabilization

0.2

Cdk5 also phosphorylates PSD-95-interacting protein Spine Associated RapGAP (SPAR), resulting in its degradation ([98], Table 2).

SIGNOR-280219

O00470

P35453

2

binding

up-regulates activity

0.499

We now show that the Hoxa-9 protein physically interacts with Meis1 proteins. Hox proteins from the other AbdB-like paralogs, Hoxa-10, Hoxa-11, Hoxd-12, and Hoxb-13, also form DNA binding complexes with Meis1b. DNA binding complexes formed by Meis1 with Hox proteins dissociate much more slowly than DNA complexes with Meis1 alone, suggesting that Hox proteins stabilize the interactions of Meis1 proteins with their DNA targets.

SIGNOR-241235

P12931

Q16827

0

dephosphorylation

down-regulates activity

0.422

SRC activation triggered by loss of PTPRO leads to c-CBL degradation.|These data corroborate that PTPRO directly dephosphorylates SRC at Y416.

SIGNOR-277004

P10911

P60953

1

guanine nucleotide exchange factor

up-regulates activity

0.777

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-260558

P08047

O43186

2

binding

up-regulates activity

0.324

Zinc finger DNA-binding domains of both Sp1 and Sp3 interact with Crx. Sp4 and Sp1 produce much higher levels of transcriptional activation when co-transfected with Crx, they may additionally act by directly increasing the rate of transcriptional initiation by the general transcriptional apparatus through their activation domains.

SIGNOR-225336

P41221

Q12857

0

transcriptional regulation

down-regulates quantity

0.2

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

SIGNOR-268877

O15530

Q05655

1

phosphorylation

up-regulates activity

0.577

PDK1 phosphorylated the activation loop sites of PKCzeta and PKCdelta in vitro and in a phosphoinositide 3-kinase (PI 3-kinase)-dependent manner in vivo in human embryonic kidney (293) cells. PKCδ was also phosphorylated in the activation loop site (T505)

SIGNOR-250269

Q00535

P04626

1

phosphorylation

up-regulates activity

0.274

Since Tyr-654 is the ERBB2 phosphorylation site on beta-catenin, this result is consistent with our hypothesis that CDK5 activates ERBB2 , which in turn phosphorylates beta-catenin on Tyr-654, leading to a shift of beta-catenin away from the adherens junction and into the nucleus where it can serve as a transcriptional co-activator.|Taken together with the results of our kinase analysis, these observations suggest that CDK5 phosphorylation of both ERBB2 and ERBB3 and AR could drive a feedback loop, in which ERBB2 and ERBB3 promotes beta-catenin transcriptional activity that then contributes to higher expression of ERBB3.

SIGNOR-279155

P53355

2

phosphorylation

down-regulates activity

0.2

The pro-apoptotic function of death-associated protein kinase is controlled by a unique inhibitory autophosphorylation-based mechanism.These results are consistent with a molecular model in which phosphorylation on ser(308) stabilizes a locked conformation of the cam-regulatory domain within the catalytic cleft and simultaneously also interferes with cam binding.

SIGNOR-110807

P24928

P28482

0

phosphorylation

down-regulates

0.311

Erk1/2 are major ser-5 kinases after h2o2 treatment. These results suggest that subsequent to h2o2 treatment, the ser-5-phosphorylated form, but not the ser-2-phosphorylated form or the unphosphorylated form, is targeted for rapid proteasomal degradation through its ubiquitination.

SIGNOR-120160

P48431

P24941

0

phosphorylation

up-regulates activity

0.394

Cdk2 physically interacts with Sox2 and phosphorylates Sox2 at Ser 39 and Ser 253 in vitro.

SIGNOR-279448

O43193

Q03113

2

binding

up-regulates activity

0.25

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-257222

Q12982

P60953

2

binding

up-regulates activity

0.709

Cdo-bnip-2-cdc42 complex stimulates cdc42 activation which in turn promotes p38 alpha/beta activity and cell differentiation.

SIGNOR-179861

P63092

P35367

2

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-256778

P36406

O14920

0

phosphorylation

down-regulates activity

0.287

Phosphorylation of ARD1 by IKKbeta reduced its growth suppression effect.

SIGNOR-279337

Q9Y2H1

2

phosphorylation

up-regulates

0.2

Ndr1/ndr2 protein kinase is activated by phosphorylation on the activation loop phosphorylation site ser281/ser282 and the hydrophobic motif phosphorylation site thr444/thr442. Autophosphorylation of ndr is responsible for phosphorylation on ser281/ser282, whereas thr444/thr442 is targeted by an upstream kinase. Here we show that mst3, a mammalian ste20-like protein kinase, is able to phosphorylate ndr protein kinase at thr444/thr442. In vitro, mst3 selectively phosphorylated thr442 of ndr2, resulting in a 10-fold stimulation of ndr activity.

SIGNOR-142518

O95837

Q96LB1

2

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-257434

Q13315

Q8WYQ5

1

phosphorylation

up-regulates quantity by stabilization

0.27

Specifically, radiation-induced ATM-dependent phosphorylation of DGCR8 at serine 677 facilitates USP51 to bind, deubiquitinate, and stabilize DGCR8, which leads to the recruitment of DGCR8 and DGCR8's binding partner RNF168 to MDC1 and RNF8 at DSBs.

SIGNOR-277307

Q5VWQ8

P40763

2

binding

down-regulates activity

0.346

DAB2IP could interact with the signal transducer and activator of transcription 3 (STAT3) via its unique PR domain and suppress STAT3 phosphorylation and transactivation, leading to the inhibition of survivin expression in PCa cells.

SIGNOR-254761

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

P35368

P17252

0

phosphorylation

down-regulates activity

0.39

Phorbol ester-induced phosphorylation of the Ser394 and Ser400 as well as GRK2-mediated phosphorylation of the Ser404, Ser408, and Ser410, resulted in the desensitization of alpha1BAR-mediated inositol phosphate response.

SIGNOR-248988

Q6ZWJ1

Q12846

2

binding

up-regulates activity

0.799

Akt2 phosphorylates Synip to regulate docking and fusion of GLUT4-containing vesicles. These data demonstrate that insulin activation of Akt2 specifically regulates the docking/fusion step of GLUT4-containing vesicles at the plasma membrane through the regulation of Synip phosphorylation and Synip-Syntaxin4 interaction.Thus, our data demonstrate that insulin-stimulated Akt2-dependent phosphorylation of Synip on serine residue 99 results in reduced binding interactions between Synip and Syntaxin4.

SIGNOR-262634

Q9HB89

O95837

2

binding

up-regulates activity

0.435

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-256894

Q99835

Q2M1P5

1

relocalization

up-regulates activity

0.632

Here, we demonstrate that Kif7, a mammalian homologue of Drosophila Costal2 (Cos2), is a cilia-associated protein that regulates signaling from the membrane protein Smoothened (Smo) to Gli transcription factorsIn response to activation of Smo Kif7 at the cilia tip may antagonize Sufu to promote activation of Gli proteins.

SIGNOR-209605

Q13164

Q06413

1

phosphorylation

up-regulates

0.766

Bmk1 dramatically enhances the transactivation activity of mef2c by phosphorylating a serine residue at amino acid position 387 in this transcription factor.

SIGNOR-53545

Q9BYF1

P01019-PRO_0000420660

1

cleavage

up-regulates quantity

0.2

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

SIGNOR-260227

P30559

P63096

2

binding

up-regulates activity

0.449

OT binds to its cognate G protein–coupled receptor (OTR) and exerts diverse effects, including stimulation (Gs) or inhibition (Gi/o) of adenylyl cyclase, stimulation of potassium channel currents (Gi), and activation of phospholipase C (Gq).

SIGNOR-270330

P04049

P12931

0

phosphorylation

up-regulates

0.605

We also show that phosphorylation of raf-1 on serine 338 by pak1 and tyrosines 340 and 341 by src relieves autoinhibition and that this occurs through a specific decrease in the binding of the raf-1 regulatory domain to its catalytic domain.

SIGNOR-97639

P15036

P02818

1

transcriptional regulation

up-regulates quantity by expression

0.2

Ets2 is expressed at high levels during the differentiation and matrix mineralization phases of MC3T3-E1 culture. In addition, several extracellular matrix (ECM) associated gene products are targets of Ets2. Some of these matrix associated genes include: bone sialoprotein, osteonectin, osteocalcin and osteopontin

SIGNOR-259875

Q14527

Q96EP1

0

polyubiquitination

down-regulates quantity by destabilization

0.482

CHFR functions as a ubiquitin ligase for HLTF to regulate its stability and functions. CHFR negatively regulates and ubiquitinates HLTF. Taken together, this is the first report identifying the regulatory mechanism of HLTF by CHFR, suggesting that CHFR-mediated downregulation of HLTF may help protect against cancer.

SIGNOR-271460

Q2M1P5

P10071

2

binding

up-regulates quantity by stabilization

0.577

These results suggest a role for Kif7 in coordinating Hh signal transduction at the tip of cilia and preventing Gli3 cleavage into a repressor form in the presence of Hh.

SIGNOR-209614

P13611

P04637

0

transcriptional regulation

up-regulates quantity by expression

0.29

By using in vitro and in vivo assays, we showed CSPG2 to be directly transactivated by p53.

SIGNOR-255441

Q00535

P29474

1

phosphorylation

down-regulates

0.371

Together, our data suggest that cdk5 can phosphorylate enos at the ser-113 site and down-regulate enos-derived no levels.

SIGNOR-164080

Q8NFZ4

Q86UL8

2

binding

up-regulates activity

0.403

S-SCAM is a member of the membrane-associated guanylate kinase (MAGUK) family of PDZ-domain-containing proteins that include the synaptic organising molecule PSD-95. The PDZ domain of S-SCAM binds to the C-terminal tail of NL2, forming a ternary complex at the cell membrane (Figure 2b). The DGC is potentially recruited to the postsynaptic membrane though a direct neurexin–dystroglycan interaction and an indirect interaction with NL2 via the synaptic scaffolding protein S-SCAM.

SIGNOR-265444

P56945

Q13882

0

phosphorylation

up-regulates

0.599

Protein-tyrosine kinase 6 promotes peripheral adhesion complex formation and cell migration by phosphorylating p130 crk-associated substrate. Tyrosine residues 165 and 664 of p130cas were both phosphorylated by ptk6 in vitro

SIGNOR-177242

P17612

P21333

1

phosphorylation

up-regulates

0.2

Site-directed mutagenesis analysis indicated that serine 2152 is the unique substrate in the c-terminal region of abp for endogenously activated pka.

SIGNOR-126659

P31749

P84022

2

binding

down-regulates

0.622

Pkb inhibits smad3 by preventing its phosphorylation, binding to smad4 and nuclear translocation. [...] Regulation of smad3 by pkb occurs through a kinase-activity-independent mechanism, resulting in a decrease in smad3-mediated transcription and protection of cells against tgf-beta-induced apoptosis.

SIGNOR-123606