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
Q9UBK2	Q99608	2	binding	up-regulates quantity by stabilization	0.326	Necdin binds and stabilizes PGC-1α\|Necdin strongly stabilizes PGC-1α by inhibiting its ubiquitin-dependent degradation. Forced expression of necdin enhances mitochondrial function in primary cortical neurons and human SH-SY5Y neuroblastoma cells to prevent mitochondrial respiratory chain inhibitor-induced degeneration.	SIGNOR-253390
Q9P2N2	P61586	1	gtpase-activating protein	down-regulates activity	0.504	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-260483
Q13627	P98177	1	phosphorylation	down-regulates	0.315	Additionally, ck1, dyrk1a, and cdk2 also phosphorylate foxos at various sites to inhibit foxos activity	SIGNOR-183677
Q9C0H5	P63000	1	gtpase-activating protein	down-regulates activity	0.501	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-260494
Q969T9	P07947	0	phosphorylation	up-regulates activity	0.304	Using dominant-negative, constitutively active mutants, RNAi, and pharmacological studies, we demonstrated that phosphorylation of WBP2 at Tyr192 and Tyr231 could be regulated by c-Src and c-Yes kinases.We further showed that abrogating WBP2 phosphorylation impaired >60% of ERα reporter activity, putatively by blocking nuclear entry of WBP2 and its interaction with ERα.	SIGNOR-273582
P15514	P00533	2	binding	up-regulates activity	0.771	ErbB ligands include: EGF, transforming growth factor (TGF)_, and amphiregulin which only bind ErbB1	SIGNOR-67000
Q12888	P49841	0	phosphorylation	up-regulates activity	0.283	Based on these observations, we hypothesized that the IR induced GSK3beta nuclear translocation may activate 53BP1 via phosphorylation at the S/T-Q motif.\|Importantly, our in vivo and in vitro data clearly indicated that GSK3\u03b2 induced the phosphorylation of 53BP1 at the Ser166 site.	SIGNOR-278226
Q13671	P00519	0	phosphorylation	up-regulates	0.751	We also report that the amino-terminal domain of rin1 contains sequences that can mediate interactions with the abl tyrosine kinase and that rin1 is itself tyrosine phosphorylated by c-abl.	SIGNOR-48142
O00327	Q92753	0	transcriptional regulation	up-regulates quantity by expression	0.478	RORβ and RORγ are also able to induce Bmal1 activity; however, RORα4 appears the most effective in inducing this activity. The ROREs in the Bmal1 promoter also bind ROR receptors. Overexpression of RORα1 and RORα4 induces Bmal1-promoter activity by interacting with these ROREs	SIGNOR-266852
P12931	Q01196	1	phosphorylation	up-regulates activity	0.412	Src phosphorylates Runx1 on one central and four C-terminal tyrosines.\|We find that activated Src synergizes with Runx1 to activate a Runx1 luciferase reporter.	SIGNOR-279656
P23771	Q99717	0	transcriptional regulation	up-regulates quantity	0.31	Chromatin immunoprecipitation (ChIP) revealed a subset of the BIG (BMP4 induced genes) signature, including Satb2, Smad6, Hand1, Gadd45γ and Gata3, that was bound by Smad1/5 in the developing mandible, revealing direct Smad-mediated regulation	SIGNOR-268943
Q13554	Q14524	1	phosphorylation	up-regulates activity	0.408	Among the sites identified, only six were previously suggested to be the targets for specific kinases using in silico and/or in vitro analyses: S36 and S525 were attributed to the regulation by PKA; S484 and S664 were assigned to the serum- and glucocorticoid-inducible kinase 3 (SGK3); and S516 and S571 were ascribed to CaMKII (reviewed in Marionneau and Abriel, 2015). In marked contrast, several previously described phosphorylation sites were not detected in the present study, including the PKA-dependent S528, the CaMKII-associated T594, the PKC-dependent S1506, the adenosine monophosphate–activated protein kinase (AMPK)–dependent T101 (Liu et al., 2019), and the six Fyn-dependent tyrosines (Ahern et al., 2005; Iqbal et al., 2018).\|The simplest interpretation of these findings is that these three phosphorylation clusters, at positions S457-S460, S483-T486, and S664-S671, are likely involved in regulating the basal and/or gating properties of native cardiac NaV1.5 channels. Conversely, the other phosphorylation sites, with lower stoichiometries, may play spatially or temporally distinct roles in the physiological or more pathophysiological regulation of channel expression or gating. \| Remarkably, this MS analysis also revealed that the vast majority of identified phosphorylation sites (at least 26) are clustered, suggesting concomitant phosphorylation and roles in regulating channel expression and/or function. Unexpectedly, however, except for S664, S667, and S671, no apparent effects of phosphomimetic or phosphosilent mutations were observed on heterologously expressed (in HEK-293 cells) NaV1.5	SIGNOR-275773
P35790	P12931	2	phosphorylation	down-regulates activity	0.336	Figure XREF_FIG shows that even though Chk phosphorylated Tyr 527 of Src to a level much lower than that of Csk, it was a much more efficient inhibitor of Src kinase activity.\|These results suggest that Chk inhibited Src with a mechanism independent of Tyr-527 phosphorylation.	SIGNOR-279731
Q9NS23	Q13043	2	binding	up-regulates	0.806	Rassf1a and mst1 co-exist as a complex localizing at microtubules throughout the cell cycle, of which the rassf1a mst1 interaction is stimulatory to the mst1 kinase activity.	SIGNOR-197744
O15552	P38405	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-256946
P40763	P23458	2	binding	up-regulates activity	0.8	The binding of lif to the lifr induces its heterodimerization with gp130. The formation of this complex results in the activation of the receptor-associated janus kinases (jaks), in the phosphorylation of receptor docking sites, and finally in the recruitment of src homology-2 (sh2) domain containing proteins such as stat3 (signal transducer and activator of transcription 3).	SIGNOR-236369
P29322	Q14938	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-268910
Q14896	P17612	0	phosphorylation	up-regulates	0.275	Phosphorylation of cmybp-c by pka speeds actomyosin interactions and contributes to increased cardiac contractility following _-adrenergic stimulation.7, 8 phosphorylation by pka is essential for proper cardiac function /for the human isoform, three pka sites were previously identified (ser275, ser284, and ser304) /our results indicate that pka phosphorylates up to four sites in both the murine and human m-domains including a novel site not previously described for either protein (ser307 for mouse and ser311 for human).	SIGNOR-163760
P49715	Q16549	0	phosphorylation	down-regulates	0.2	Addition of active p38a induced phosphorylation of wild-type c/ebp_? (c/ebp_?WT) on serine 21	SIGNOR-186202
O14733	Q13158	1	phosphorylation	down-regulates activity	0.497	The results clearly show that fadd phosphorylation at ser194 affects functions both upstream and downstream of the mekk1/mkk7/jnk1 pathway and is closely associated with chemosensitivity in prostate cancer cells	SIGNOR-123164
Q13467	O14640	2	binding	up-regulates activity	0.659	Upon ligand binding, DVL proteins are recruited to Frizzled receptors at the plasma membrane and co-recruit cytoplasmic transducers, such as Axin, CK1 and GSK3 binding protein (GBP), presumably along with their partners, to promote ?-catenin-dependent signalling.	SIGNOR-258957
P12931	P49023	1	phosphorylation	up-regulates activity	0.808	Here, we demonstrate that Src kinase directly phosphorylates Y88 paxillin\|In this study, we also show how pY88 paxillin transduces a signal to activate Akt	SIGNOR-263977
P41221	Q14332	2	binding	down-regulates	0.766	Fz2 was also required for the wnt3a-dependent accumulation of beta-catenin, and wnt5a competed with wnt3a for binding to fz2 in vitro and in intact cells, thereby inhibiting the beta-catenin pathway.	SIGNOR-23441
P29350	O43318	1	dephosphorylation	down-regulates activity	0.295	Mechanistically, the association of EHEC Tir with SHP-1 facilitated the recruitment of SHP-1 to TAK1 and inhibited TAK1 phosphorylation, which then negatively regulated K63-linked polyubiquitination of TAK1 and downstream signal transduction.\|SHP-1 inhibits TAK1 activity to down-regulate signal transduction and subsequent cytokine production.Innate immune responses are achieved by the activation of several pathogen-recognition receptors (PRPs), including TLRs, retinoic acid inducible gene I (RIG-I)-like receptors (RLRs) and nucleotide-binding oligomerization domain (NOD)-like receptors (NLRs).	SIGNOR-277128
P33032	Q96G30	2	binding	down-regulates activity	0.502	We report that MRAP and MRAP2 can interact with all 5 MCRs. This interaction results in MC2R surface expression and signaling. In contrast, MRAP and MRAP2 can reduce MC1R, MC3R, MC4R, and MC5R responsiveness to [Nle4,D-Phe7]alpha-melanocyte-stimulating hormone (NDP-MSH). MRAP and MRAP2 can reduce the surface expression of MC4R and also the signaling of this receptor. we observed a significant decrease in the cell-surface expression of MC4R and MC5R in the presence of MRAP and MRAP2. It is interesting that MRAP and MRAP2 have opposite effects in the modulation of different MCR family members.	SIGNOR-252369
P30279	P01106	0	transcriptional regulation	up-regulates quantity by expression	0.45	C-myc directly activates transcription of cyclin d1, cyclin d2 and cdk4, and leads to cdk 4/6 activation.	SIGNOR-27446
P02545	P17252	0	phosphorylation	up-regulates activity	0.362	Mutation of both Ser-403/Ser-404 within a PKC motif flanking the nuclear localization signal inhibits transport of mutant lamin A to the nucleus in 64% of the cells. It is proposed that phosphorylation of the motif in vivo positively regulates nuclear localization together with the nuclear localization sequence.	SIGNOR-248904
P48729	Q9H6E5	1	phosphorylation	up-regulates activity	0.267	We identified a phosphorylated residue (serine 6, S6) on Star-PAP in the zinc finger region, the domain required for PIPKIα interaction. We show that S6 is phosphorylated by CKIα within the nucleus which is required for Star-PAP nuclear retention and interaction with PIPKIα.	SIGNOR-273619
P01160	Q9Y6Y1	0	transcriptional regulation	up-regulates quantity by expression	0.429	CAMTA1 itself stimulates the expression of the anti-proliferative peptide NPPA.	SIGNOR-261570
P16871	P13232	2	binding	up-regulates	0.914	This receptor (il-7r) is a heterodimer consisting of the il-7r chain and the common cytokine ? -chain.	SIGNOR-163548
Q6ZMZ3	Q9H3D4	0	transcriptional regulation	up-regulates quantity by expression	0.2	Here we show that in the developing skin, epidermal progenitor cells of mice lacking p63 transcription factor display alterations in the nuclear shape accompanied by a marked decrease in expression of several nuclear envelope-associated components (Lamin B1, Lamin A/C, Sun1, Nesprin-3, Plectin) compared with controls. Furthermore, chromatin immunoprecipitation-quantitative PCR assay showed enrichment of p63 on Sun1, Syne3, and Plec promoters, suggesting them as p63 targets.	SIGNOR-263280
Q13571	P46934	0	ubiquitination	up-regulates activity	0.476	These results suggest that LAPTM5 ubiquitination is mediated by Nedd4.\|Thus, Nedd4 promotes the recruitment of GGA3 to LAPTM5, allowing LAPTM5 translocation from the Golgi to the lysosome with the aid of GGA3.	SIGNOR-278768
Q15628	Q13546	2	binding	up-regulates activity	0.937	We show that tradd interacts strongly with rip;rip is a serinethreonine kinase that is recruited by tradd to tnfr1 in a tnf-dependent process.	SIGNOR-40043
P43026	Q9UHF7	1	relocalization	up-regulates activity	0.306	Treatment of cells with Gdf5 enhanced Trps1 protein levels and phosphorylation of p38 mitogen-activated protein kinase (MAPK) in a dose-dependent manner. Nuclear translocation of Trps1 was also induced by Gdf5. These effects were blocked by a dominant negative form of activin-linked kinase 6 (dn-Alk6) and by SB203580, an inhibitor of the p38 MAPK pathway. Conversely, Gdf5 expression was suppressed by the over-expression of Trps1.	SIGNOR-251867
Q96GD4	Q9H0H5	1	phosphorylation	up-regulates activity	0.78	It was found that the 5A fragment in which five Ser/Thr residues were substituted with Ala (S144A/T145A/S185A/T186A/S187A) fully prevented phosphorylation (Fig. 5B), confirming that Aurora B primarily phosphorylates five Ser/Thr residues in the basic region of MgcRacGAP. \| the strong phosphorylation of the basic region of MgcRacGAP by Aurora B kinase was demonstrated, and this phosphorylation prevents the inhibition of MgcRacGAP GAP activity by PRC1	SIGNOR-250590
Q12959	Q9UQM7	0	phosphorylation	down-regulates activity	0.649	Synapse-associated protein 97 (SAP97), a member of membrane-associated guanylate kinase protein family, has been implicated in the processes of targeting ionotropic glutamate receptors at postsynaptic sites. \| We show here that SAP97 is directly associated with NR2A through its PDZ1 domain, and CaMKII-dependent phosphorylation of SAP97-Ser-232 disrupts NR2A interaction both in an in vitro pull-out assay and in transfected COS-7 cells. Moreover, expression of SAP97(S232D) mutant has effects similar to those observed upon constitutively activating CaMKII.	SIGNOR-250618
P08047	P07288	1	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-253664
O95352	Q9BXW4	2	binding	up-regulates activity	0.789	Lc3-i is activated by the same atg7 involved in atg12 conjugation, transferred to atg3, a second e2-like enzyme, and finally conjugated to pe	SIGNOR-191540
Q01970	P41279	0	phosphorylation	up-regulates activity	0.2	Additionally, we found that PAR1-induced Ca2+ signals are transduced through Tpl2, which activates phospholipase C\u03b23 by phosphorylation at Ser537.\|These findings raised the question whether Tpl2, which phosphorylates PLCbeta 3 at Ser537 (this report) regulates Ca 2+ signaling in thrombin stimulated cells through phosphorylation of PLCbeta 3 at this site.	SIGNOR-278519
Q13043	Q9UL54	0	phosphorylation	up-regulates	0.279	In addition, the thousand-and-one (tao) amino acids kinase or taok1 3 has been shown to directly phosphorylate and activate hpo or mst1/2	SIGNOR-201330
O95837	Q99500	2	binding	up-regulates activity	0.385	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-257437
P10636	Q9UM73	0	phosphorylation	up-regulates quantity	0.2	All these results point to the critical role played by ALK in the phosphorylation and accumulation of tau and in the associated memory impairment seen in 3xTg-AD mice.	SIGNOR-279318
Q92547	O95071	0	polyubiquitination	down-regulates quantity by destabilization	0.462	Using an in vitro reconstitution, specific E2 (ubiquitin-conjugating) enzymes (human UbcH4, UbcH5B, and UbcH5C) transferred ubiquitin molecules to hHYD, leading to the ubiquitination of TopBP1. TopBP1 was usually ubiquitinated and degraded by the proteosome, whereas X-irradiation diminished the ubiquitination of TopBP1 probably via the phosphorylation, resulting in the stable colocalization of up-regulated TopBP1 with gamma-H2AX nuclear foci in DNA breaks.	SIGNOR-272667
Q8TEW0	O14965	0	phosphorylation	up-regulates	0.35	Aurora a interacts directly with the atypical protein kinase c binding domain of par3 and phosphorylates it at serine 962. The phosphorylation of par3 at serine 962 contributes to its function in the establishment of neuronal polarity.	SIGNOR-188398
Q15077	P19086	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-257189
O60260	Q9NX47	0	ubiquitination	down-regulates quantity by destabilization	0.2	MITOL promotes cell survival by degrading Parkin during mitophagy.\|Mechanistically, MITOL mediates ubiquitination of Parkin at lysine 220 residue, which promotes its proteasomal degradation, and thereby fine-tunes mitophagy by controlling the quantity of Parkin.	SIGNOR-278554
P17480	Q8IWS0	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
Q92890	Q9UKV5	2	binding	up-regulates activity	0.2	Here we show that Ufd1 directly interacts with gp78 and functions as a cofactor. Ufd1 enhances the E3 activity of gp78, accelerates the ubiquitination and degradation of reductase, and eventually promotes receptor-mediated uptake of low-density lipoprotein.	SIGNOR-252425
P27448	Q8IVT5	1	phosphorylation	down-regulates activity	0.642	C-TAK1 phosphorylates KSR1 at S392, forming a 14-3-3 binding site.\|In mammalian cells, C-TAK1 has been shown to negatively regulate KSR1 by phosphorylation of Ser392.	SIGNOR-279225
P01019	P00797	2	binding	up-regulates activity	0.928	Renin is an aspartic protease that enzymatically cleaves its substrate angiotensinogen, which is produced by the liver, to form an inactive peptide: angiotensin (Ang)I or Ang (1–10).	SIGNOR-260224
Q5JTV8	P08670	2	binding	up-regulates activity	0.2	Co-immune precipitation studies revealed association between vimentin and torsinA in a complex. these studies suggest that mutant torsinA interferes with cytoskeletal events involving vimentin, possibly by restricting movement of these particles/filaments, and hence may affect development of neuronal pathways in the brain.	SIGNOR-261313
P12931	Q13002	1	phosphorylation	up-regulates activity	0.372	GluK2 binds to Src, and the tyrosine residue at position 590 (Y590) on GluK2 is a major site of phosphorylation by Src kinases. GluK2 phosphorylation at Y590 is responsible for increases in whole-cell currents and calcium influx in response to transient kainate stimulation.	SIGNOR-276850
Q13131	Q13554	0	phosphorylation	up-regulates	0.2	These data indicate that the camkks function in intact cells as ampkks, predicting wider roles for these kinases in regulating ampk activity in vivo.	SIGNOR-138360
P24864	P49841	0	phosphorylation	down-regulates	0.445	Our experiments suggest that gsk3 is the kinase primarily responsible for phosphorylation of cyclin e on t380	SIGNOR-118563
Q16236	P13640	1	transcriptional regulation	up-regulates quantity by expression	0.286	NFE2L2 is stabilized and translocates to the nucleus, where it dimerizes with sMAF proteins. This complex binds to AREs to mediate the transcription of genes involved in iron metabolism, GSH metabolism, and ROS detoxification. The expression of MT1G during ferroptosis is regulated by the NFE2L2 signaling pathway. In the context of cancer, particularly HCC, the upregulation of MT1G has been linked to resistance against sorafenib, a kinase inhibitor commonly used in cancer therapy	SIGNOR-279866
Q93009	Q96EP1	1	deubiquitination	up-regulates quantity by stabilization	0.432	In this study, we identified USP7 (also known as HAUSP), which is a member of a family of proteins that cleave polyubiquitin chains and/or ubiquitin precursors, as an interacting protein with Chfr by immunoaffinity purification and mass spectrometry, and their interaction greatly increases the stability of Chfr. In fact, USP7 can remove ubiquitin moiety from the autoubiquitinated Chfr both in vivo and in vitro, which results in the accumulation of Chfr in the cell. USP7 mediates deubiquitination of Chfr.	SIGNOR-271462
O15392	Q96GD4	0	phosphorylation	down-regulates	0.795	Phosphorylation by aurora-b negatively regulates survivin function . hat survivin is phosphorylated at t117 during mitosis, and once phosphorylated, dephosphorylation is crucial for chromosome congression and progression into anaphaseduring mitosis	SIGNOR-154569
Q8TEL6	P01106	2	binding	down-regulates quantity by destabilization	0.35	We characterize a new Myc-interacting factor, TRPC4AP (transient receptor potential cation channel, subfamily C, member 4-associated protein)/TRUSS (tumor necrosis factor receptor-associated ubiquitous scaffolding and signaling protein), which is the receptor for a DDB1 (damage-specific DNA-binding protein 1)-CUL4 (Cullin 4) E3 ligase complex for selective Myc degradation through the proteasome. TRPC4AP/TRUSS binds specifically to the Myc C terminus and promotes its ubiquitination and destruction through the recognition of evolutionarily conserved domains in the Myc N terminus.	SIGNOR-271963
Q7Z589	P51587	2	binding	down-regulates activity	0.2	The EMSY protein interacts precisely with a highly conserved transactivating region at the N terminus of the breast cancer protein BRCA2, and has endogenous transcriptional repressor activity when recruited to a high basal promoter. We have suggested that the independent activation domain of BRCA2 within exon 3 might have some role in transcription (Milner et al., 1997). The identification of the repressor protein EMSY, which binds and silences this domain, is consistent with such a function.	SIGNOR-263915
P28069	P78337	2	binding	up-regulates activity	0.471	A novel OTX-related homeodomain transcription factor has been identified on the basis of its ability to interact with the transactivation domain of the pituitary-specific POU domain protein, Pit-1. P-OTX is able to independently activate and to synergize with Pit-1 on pituitary-specific target gene promoters.	SIGNOR-219740
P51812	P28482	0	phosphorylation	up-regulates	0.728	Erk-activates the rsk family of serine/threonine kinases,rsk1, rsk2, and rsk3.	SIGNOR-161518
O75914	Q99523	1	phosphorylation	down-regulates activity	0.2	PAKs specifically phosphorylate Ser15 of the sortilin-cd and alter its trafficking. It can be concluded that PAK1-3 may indeed instigate the phosphorylation of sortilin and that they target a single serine residue (Ser15) located in the kinase domain-binding site of the sortilin-cd. Full-length sortilins with the serine at position 793 (residue 15 in the cytoplasmic domain) (for the sequence, see Fig. 2). Phosphorylation (Ser15) downregulates the sortilin–AP-1 interaction.	SIGNOR-273719
Q9UHD2	Q9BRV8	1	phosphorylation	down-regulates quantity	0.718	Mechanism of endogenous regulation of the type I interferon response by suppressor of I\u03baB kinase epsilon (SIKE), a novel substrate of TANK-binding kinase 1 (TBK1).\|TBK1 phosphorylation of IRF3 and SIKE displayed negative cooperativity.	SIGNOR-280152
P53355	P28482	2	binding	down-regulates	0.565	Conversely, dapk promotes the cytoplasmic retention of erk, thereby inhibiting erk signaling in the nucleus.	SIGNOR-132610
P15514	P78536	0	cleavage	up-regulates activity	0.448	ADAM17 is involved in the release and activation of several growth factors and cytokine receptor ligands. Among the growth factors activated by ADAM17 are TGF-alpha, amphiregulin, epiregulin and HB-EGF	SIGNOR-259842
P54829	P42262	1	dephosphorylation	down-regulates activity	0.412	One study showed that stimulation of the metabotrophic glutamate receptor mGluR5 leads to a STEP mediated tyrosine dephosphorylation of GluA2 and internalization of GluA1 and GluA2, although the tyrosine residue on GluA2 that is dephosphorylated by STEP remains unidentified.	SIGNOR-277040
Q07869	P27361	0	phosphorylation	up-regulates activity	0.601	We now demonstrate that amino acids 1-92 of hPPARalpha contain an activation function (AF)-1-like domain, which is further activated by insulin through a pathway involving the mitogen-activated protein kinases p42 and p44. Further analysis of the amino-terminal region of PPARalpha revealed that the insulin-induced trans-activation occurs through the phosphorylation of two mitogen-activated protein kinase sites at positions 12 and 21, both of which are conserved across evolution.	SIGNOR-249474
O75581	O00744	2	binding	up-regulates activity	0.609	Wnt proteins bind to the frizzled receptors and lrp5/6 co-receptors, and through stabilizing the critical mediator betBeta-catenin, initiate a complex signaling cascade that plays an important role in regulating cell proliferation and differentiation.	SIGNOR-131631
Q15327	Q7Z570	0	transcriptional regulation	up-regulates quantity by expression	0.2	ZNF804A has been implicated in susceptibility to schizophrenia by several genome-wide association studies (GWAS), follow-up association studies and meta-analyses. ZNF804A was identified as a schizophrenia-associated gene by GWAS and was predicted to play a role in DNA binding and transcription To identify the genes that are affected by ZNF804A, we manipulated the expression of the ZNF804A protein in HEK293 human embryonic kidney cell lines and performed a cDNA microarray analysis followed by qPCR. We found that ZNF804A-overexpression up-regulated four genes (ANKRD1, INHBE, PIK3AP1, and DDIT3) and down-regulated three genes (CLIC2, MGAM, and BIRC3).	SIGNOR-269461
A6NJZ7	Q9UJD0	2	binding	down-regulates activity	0.265	SH3 domains of RBPs interact with RIMs. The enhancement of depolarization-induced secretion in PC12 cells by fusion proteins that suppress the associations of RBPs with RIMs and α1 suggests that RBPs may repress RIMs, either directly or through associated proteins.	SIGNOR-264372
P01137	P36897	2	binding	up-regulates activity	0.846	TGFbeta signals are transmitted via a cell surface receptor complex consisting of the TGFbeta type I receptor (TbetaRI) and TGFbeta type II receptor (TbetaRII). To initiate signal transduction, TGFbeta binds to TbetaRII, which in turn recruits TbetaRI, leading to the formation of a tetrameric receptor complex.	SIGNOR-249548
Q01860	Q9Y243	0	phosphorylation	up-regulates quantity by stabilization	0.257	Here we show that in ECCs, Akt phosphorylated the master pluripotency factor Oct4 at threonine 235, and that the levels of phosphorylated Oct4 in ECCs correlated with resistance to apoptosis and tumorigenic potential. Phosphorylation of Oct4 increased its stability and facilitated its nuclear localization and its interaction with Sox2, which promoted the transcription of the core stemness genes POU5F1 and NANOG.	SIGNOR-242107
P84022	P05412	2	binding	down-regulates activity	0.75	These results indicate that interaction between Smad3 and c-Jun may repress Smad3 transcriptional activity.	SIGNOR-256284
O15393	P10275	0	transcriptional regulation	up-regulates quantity by expression	0.575	The prostate-specific TMPRSS2 gene, while upregulated by AR activity in luminal cells, is also transcribed in basal populations, confirming that AR acts as an expression modulator.	SIGNOR-253687
P43403	Q16539	2	phosphorylation	up-regulates activity	0.476	Lck, Fyn, and Zap70 activate p38 even in the absence of Tyr182 phosphorylation.p38 is a substrate for Fyn, Lck and Zap70.Thus, T cell Src family kinases and Zap70 activate p38 by phosphorylating Tyr323.	SIGNOR-276030
P61073	P14174	2	binding	up-regulates activity	0.371	We identify the chemokine receptors CXCR2 and CXCR4 as functional receptors for MIF [] By activating both CXCR2 and CXCR4, MIF displays chemokine-like functions and acts as a major regulator of inflammatory cell recruitment and atherogenesis.	SIGNOR-252062
Q00987	P67775	0	dephosphorylation	up-regulates activity	0.455	cyclin G also binds in vivo and in vitro to Mdm2 and markedly stimulates the ability of PP2A to dephosphorylate Mdm2 at T216. Consistent with these data, cyclin G null cells have both Mdm2 that is hyperphosphorylated at T216 and markedly higher levels of p53 protein when compared to wild-type cells	SIGNOR-248636
P52333	P42229	1	phosphorylation	up-regulates	0.854	For these assays, coexpression of wt jak3 with stat5a was found to result in tyrosine phosphorylation of stat5a (lane 2) mediated by jak3, since stat5a coexpressed with the kinase-inactive k855a mutant form of jak3 was not tyrosine phosphorylated.	SIGNOR-182817
Q9NR19	Q14457	1	transcriptional regulation	up-regulates quantity by expression	0.2	As expected, we found that glucose deprivation induced the binding of TFEB (Figure S4C) and ACSS2 (Figure S4D) to the promoter regions of MAP1LC3B, ATG3, and WIPI-1 as well as mRNA (Figure 3H) and protein (Figure 3I) expression of these genes;	SIGNOR-276561
O75582	P84243	1	phosphorylation	down-regulates activity	0.2	Phosphorylation at ser-11 (h3s10ph) by rps6ka4 and rps6ka5 is important during interphase because it enables the transcription of genes following external stimulation, like mitogens, stress, growth factors or uv irradiation and result in the activation of genes, such as c-fos and c-jun.	SIGNOR-119233
Q02763	P35590	1	phosphorylation	up-regulates activity	0.348	Thus, Tie2 was able to induce Tie1 phosphorylation.\|When cotransfected, Tie2 formed heteromeric complexes with Tie1, enhanced Tie1 activation, and induced phosphorylation of a kinase-inactive Tie1 in a ligand-dependent manner.	SIGNOR-279769
P11802	P05067	1	phosphorylation	down-regulates quantity by destabilization	0.258	These include a significant increase in APP phosphorylation at Thr 668 by cdk2, cdk4, and cdk5, which increases its beta-amyloid production and APP proteolysis by the activated caspases during cell cycle ( xref ; xref ; xref ; xref ).	SIGNOR-280214
Q96BA8	O43462	0	cleavage	up-regulates	0.568	Cleavage of oasis by site-1 and site-2 proteases / oasis is cleaved at the membrane under er stress conditions and that its cleaved n-terminal domain translocates into the nucleus;and then activates transcription of target genes	SIGNOR-143820
Q96GF1	O14641	1	polyubiquitination	down-regulates quantity by destabilization	0.466	The E3 ligase RNF185 negatively regulates osteogenic differentiation by targeting Dvl2 for degradation. Overexpression of RNF185 decreases the exogenous and endogenous level of Dvl2, promotes the ubiquitination and degradation of Dvl2	SIGNOR-272173
P33032	P63096	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-257070
P04626	P04626	2	phosphorylation	up-regulates	0.2	Stimulation of these molecules, however, failed to induce efficient cell migration in the absence of neu/erbb2 phosphorylation at tyr 1201 or tyr 1227	SIGNOR-124860
Q5T0W9	P48729	2	binding	up-regulates quantity	0.344	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-273746
P10451	P05186	0	dephosphorylation	down-regulates activity	0.442	This result suggests that endogenous mouse TNAP dephosphorylates OPN in osteoblasts and that overexpressed human TNAP dephosphorylates OPN, compensating for the lack of endogenous TNAP in [Col1a1-Tnap +/\u2212 ;Alpl \u2212/\u2212 ] cells.	SIGNOR-277045
P35222	Q06945	2	binding	up-regulates activity	0.592	We have demonstrated that Sox17 and Sox4 can directly interact with β-catenin and TCF/LEF proteins.Sox4 enhances β-catenin/TCF activity and the proliferation of SW480 cells.In contrast, Sox4 may function to stabilize β-catenin protein.	SIGNOR-256138
Q13547	P49715	1	transcriptional regulation	down-regulates	0.436	These data suggest that c/ebp beta activates a single unified pathway of adipogenesis involving its stimulation of ppargamma expression, which then activates c/ebp alpha expression by dislodging hdac1 from the promoter for degradation in the proteasome	SIGNOR-210013
Q12857	Q14393	1	transcriptional regulation	down-regulates quantity	0.2	By integrating transcriptomic profiling (RNA-seq) of Nfia- and Nfix-deficient GNPs with epigenomic profiling (ChIP-seq against NFIA, NFIB and NFIX, and DNase I hypersensitivity assays), we reveal that these transcription factors share a large set of potential transcriptional targets, suggestive of complementary roles for these NFI family members in promoting neural development	SIGNOR-268876
P16298	O95644	1	relocalization	up-regulates	0.724	The ca2+ dependent phosphatase calcineurin induces cardiac and skeletal muscle hypertrophy by a process that involves nf-at nuclear translocation, and activation of mef2c.	SIGNOR-84047
P02708	O14905	2	binding	up-regulates	0.2	We identified five wnts (wnt9a, wnt9b, wnt10b, wnt11, and wnt16) that are able to stimulate achr clustering, of which wnt9a and wnt11 are expressed abundantly in developing muscles.	SIGNOR-195978
P84022	Q9GZU7	0	dephosphorylation	up-regulates activity	0.433	SCP1 Dephosphorylates Smad2/3 in the Linkers\|MAPK-mediated linker phosphorylation appears to have a dual role in Smad2/3 regulation. Mitogens and hyperactive Ras result in extracellular signal-regulated kinase (ERK)-mediated phosphorylation of Smad3 at Ser-204, Ser-208, and Thr-179 and of Smad2 at Ser-245/250/255 and Thr-220. Mutation of these sites increases the ability of Smad3 to activate target genes, suggesting that MAPK phosphorylation of Smad3 is inhibitory (11, 12). However, in contrast, ERK-dependent phosphorylation of Smad2 at Thr-8 enhances its transcriptional activity	SIGNOR-248792
P11831	Q9ULH7	2	binding	up-regulates activity	0.2	MKL2 binds to and activates SRF similar to myocardin and MKL1.	SIGNOR-237671
Q14721	P23469	0	dephosphorylation	down-regulates activity	0.355	Hypomyelination and increased activity of voltage-gated K(+) channels in mice lacking protein tyrosine phosphatase epsilon	SIGNOR-248450
P14316	P33076	1	transcriptional regulation	up-regulates quantity by expression	0.525	In addition to IRF-1, IRF-2, another member of the IRF family, also activates the human CIITA type IV promoter, and IRF-2 cooperates with IRF-1 to activate the promoter in transient transfection assays.	SIGNOR-271681
P09619	P62993	2	binding	up-regulates	0.68	A pathway leading to activation of the gtp-binding protein ras involves the adaptor molecule grb2. Here we show that tyr-716, a novel autophosphorylation site in the pdgf beta-receptor kinase insert, mediates direct binding of grb2 in vitro and in vivo.	SIGNOR-34765
O00329	P21860	2	binding	up-regulates	0.416	Pi3k is the sole binding partner to six tyrosines of erbb3 and one in erbb4.	SIGNOR-146867
P68400	Q96NY9	1	phosphorylation	up-regulates activity	0.2	Here, we show that the CK2 kinase phosphorylates MUS81 at Serine 87 in late-G2/mitosis, and upon mild replication stress. Phosphorylated MUS81 interacts with SLX4, and this association promotes the function of the MUS81 complex.	SIGNOR-273626

Q9UBK2

Q99608

2

binding

up-regulates quantity by stabilization

0.326

Necdin binds and stabilizes PGC-1α|Necdin strongly stabilizes PGC-1α by inhibiting its ubiquitin-dependent degradation. Forced expression of necdin enhances mitochondrial function in primary cortical neurons and human SH-SY5Y neuroblastoma cells to prevent mitochondrial respiratory chain inhibitor-induced degeneration.

SIGNOR-253390

Q9P2N2

P61586

1

gtpase-activating protein

down-regulates activity

0.504

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-260483

Q13627

P98177

1

phosphorylation

down-regulates

0.315

Additionally, ck1, dyrk1a, and cdk2 also phosphorylate foxos at various sites to inhibit foxos activity

SIGNOR-183677

Q9C0H5

P63000

1

gtpase-activating protein

down-regulates activity

0.501

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-260494

Q969T9

P07947

0

phosphorylation

up-regulates activity

0.304

Using dominant-negative, constitutively active mutants, RNAi, and pharmacological studies, we demonstrated that phosphorylation of WBP2 at Tyr192 and Tyr231 could be regulated by c-Src and c-Yes kinases.We further showed that abrogating WBP2 phosphorylation impaired >60% of ERα reporter activity, putatively by blocking nuclear entry of WBP2 and its interaction with ERα.

SIGNOR-273582

P15514

P00533

2

binding

up-regulates activity

0.771

ErbB ligands include: EGF, transforming growth factor (TGF)_, and amphiregulin which only bind ErbB1

SIGNOR-67000

Q12888

P49841

0

phosphorylation

up-regulates activity

0.283

Based on these observations, we hypothesized that the IR induced GSK3beta nuclear translocation may activate 53BP1 via phosphorylation at the S/T-Q motif.|Importantly, our in vivo and in vitro data clearly indicated that GSK3\u03b2 induced the phosphorylation of 53BP1 at the Ser166 site.

SIGNOR-278226

Q13671

P00519

0

phosphorylation

up-regulates

0.751

We also report that the amino-terminal domain of rin1 contains sequences that can mediate interactions with the abl tyrosine kinase and that rin1 is itself tyrosine phosphorylated by c-abl.

SIGNOR-48142

O00327

Q92753

0

transcriptional regulation

up-regulates quantity by expression

0.478

RORβ and RORγ are also able to induce Bmal1 activity; however, RORα4 appears the most effective in inducing this activity. The ROREs in the Bmal1 promoter also bind ROR receptors. Overexpression of RORα1 and RORα4 induces Bmal1-promoter activity by interacting with these ROREs

SIGNOR-266852

P12931

Q01196

1

phosphorylation

up-regulates activity

0.412

Src phosphorylates Runx1 on one central and four C-terminal tyrosines.|We find that activated Src synergizes with Runx1 to activate a Runx1 luciferase reporter.

SIGNOR-279656

P23771

Q99717

0

transcriptional regulation

up-regulates quantity

0.31

Chromatin immunoprecipitation (ChIP) revealed a subset of the BIG (BMP4 induced genes) signature, including Satb2, Smad6, Hand1, Gadd45γ and Gata3, that was bound by Smad1/5 in the developing mandible, revealing direct Smad-mediated regulation

SIGNOR-268943

Q13554

Q14524

1

phosphorylation

up-regulates activity

0.408

Among the sites identified, only six were previously suggested to be the targets for specific kinases using in silico and/or in vitro analyses: S36 and S525 were attributed to the regulation by PKA; S484 and S664 were assigned to the serum- and glucocorticoid-inducible kinase 3 (SGK3); and S516 and S571 were ascribed to CaMKII (reviewed in Marionneau and Abriel, 2015). In marked contrast, several previously described phosphorylation sites were not detected in the present study, including the PKA-dependent S528, the CaMKII-associated T594, the PKC-dependent S1506, the adenosine monophosphate–activated protein kinase (AMPK)–dependent T101 (Liu et al., 2019), and the six Fyn-dependent tyrosines (Ahern et al., 2005; Iqbal et al., 2018).|The simplest interpretation of these findings is that these three phosphorylation clusters, at positions S457-S460, S483-T486, and S664-S671, are likely involved in regulating the basal and/or gating properties of native cardiac NaV1.5 channels. Conversely, the other phosphorylation sites, with lower stoichiometries, may play spatially or temporally distinct roles in the physiological or more pathophysiological regulation of channel expression or gating. | Remarkably, this MS analysis also revealed that the vast majority of identified phosphorylation sites (at least 26) are clustered, suggesting concomitant phosphorylation and roles in regulating channel expression and/or function. Unexpectedly, however, except for S664, S667, and S671, no apparent effects of phosphomimetic or phosphosilent mutations were observed on heterologously expressed (in HEK-293 cells) NaV1.5

SIGNOR-275773

P35790

P12931

2

phosphorylation

down-regulates activity

0.336

Figure XREF_FIG shows that even though Chk phosphorylated Tyr 527 of Src to a level much lower than that of Csk, it was a much more efficient inhibitor of Src kinase activity.|These results suggest that Chk inhibited Src with a mechanism independent of Tyr-527 phosphorylation.

SIGNOR-279731

Q9NS23

Q13043

2

binding

up-regulates

0.806

Rassf1a and mst1 co-exist as a complex localizing at microtubules throughout the cell cycle, of which the rassf1a mst1 interaction is stimulatory to the mst1 kinase activity.

SIGNOR-197744

O15552

P38405

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-256946

P40763

P23458

2

binding

up-regulates activity

0.8

The binding of lif to the lifr induces its heterodimerization with gp130. The formation of this complex results in the activation of the receptor-associated janus kinases (jaks), in the phosphorylation of receptor docking sites, and finally in the recruitment of src homology-2 (sh2) domain containing proteins such as stat3 (signal transducer and activator of transcription 3).

SIGNOR-236369

P29322

Q14938

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-268910

Q14896

P17612

0

phosphorylation

up-regulates

0.275

Phosphorylation of cmybp-c by pka speeds actomyosin interactions and contributes to increased cardiac contractility following _-adrenergic stimulation.7, 8 phosphorylation by pka is essential for proper cardiac function /for the human isoform, three pka sites were previously identified (ser275, ser284, and ser304) /our results indicate that pka phosphorylates up to four sites in both the murine and human m-domains including a novel site not previously described for either protein (ser307 for mouse and ser311 for human).

SIGNOR-163760

P49715

Q16549

0

phosphorylation

down-regulates

0.2

Addition of active p38a induced phosphorylation of wild-type c/ebp_? (c/ebp_?WT) on serine 21

SIGNOR-186202

O14733

Q13158

1

phosphorylation

down-regulates activity

0.497

The results clearly show that fadd phosphorylation at ser194 affects functions both upstream and downstream of the mekk1/mkk7/jnk1 pathway and is closely associated with chemosensitivity in prostate cancer cells

SIGNOR-123164

Q13467

O14640

2

binding

up-regulates activity

0.659

Upon ligand binding, DVL proteins are recruited to Frizzled receptors at the plasma membrane and co-recruit cytoplasmic transducers, such as Axin, CK1 and GSK3 binding protein (GBP), presumably along with their partners, to promote ?-catenin-dependent signalling.

SIGNOR-258957

P12931

P49023

1

phosphorylation

up-regulates activity

0.808

Here, we demonstrate that Src kinase directly phosphorylates Y88 paxillin|In this study, we also show how pY88 paxillin transduces a signal to activate Akt

SIGNOR-263977

P41221

Q14332

2

binding

down-regulates

0.766

Fz2 was also required for the wnt3a-dependent accumulation of beta-catenin, and wnt5a competed with wnt3a for binding to fz2 in vitro and in intact cells, thereby inhibiting the beta-catenin pathway.

SIGNOR-23441

P29350

O43318

1

dephosphorylation

down-regulates activity

0.295

Mechanistically, the association of EHEC Tir with SHP-1 facilitated the recruitment of SHP-1 to TAK1 and inhibited TAK1 phosphorylation, which then negatively regulated K63-linked polyubiquitination of TAK1 and downstream signal transduction.|SHP-1 inhibits TAK1 activity to down-regulate signal transduction and subsequent cytokine production.Innate immune responses are achieved by the activation of several pathogen-recognition receptors (PRPs), including TLRs, retinoic acid inducible gene I (RIG-I)-like receptors (RLRs) and nucleotide-binding oligomerization domain (NOD)-like receptors (NLRs).

SIGNOR-277128

P33032

Q96G30

2

binding

down-regulates activity

0.502

We report that MRAP and MRAP2 can interact with all 5 MCRs. This interaction results in MC2R surface expression and signaling. In contrast, MRAP and MRAP2 can reduce MC1R, MC3R, MC4R, and MC5R responsiveness to [Nle4,D-Phe7]alpha-melanocyte-stimulating hormone (NDP-MSH). MRAP and MRAP2 can reduce the surface expression of MC4R and also the signaling of this receptor. we observed a significant decrease in the cell-surface expression of MC4R and MC5R in the presence of MRAP and MRAP2. It is interesting that MRAP and MRAP2 have opposite effects in the modulation of different MCR family members.

SIGNOR-252369

P30279

P01106

0

transcriptional regulation

up-regulates quantity by expression

0.45

C-myc directly activates transcription of cyclin d1, cyclin d2 and cdk4, and leads to cdk 4/6 activation.

SIGNOR-27446

P02545

P17252

0

phosphorylation

up-regulates activity

0.362

Mutation of both Ser-403/Ser-404 within a PKC motif flanking the nuclear localization signal inhibits transport of mutant lamin A to the nucleus in 64% of the cells. It is proposed that phosphorylation of the motif in vivo positively regulates nuclear localization together with the nuclear localization sequence.

SIGNOR-248904

P48729

Q9H6E5

1

phosphorylation

up-regulates activity

0.267

We identified a phosphorylated residue (serine 6, S6) on Star-PAP in the zinc finger region, the domain required for PIPKIα interaction. We show that S6 is phosphorylated by CKIα within the nucleus which is required for Star-PAP nuclear retention and interaction with PIPKIα.

SIGNOR-273619

P01160

Q9Y6Y1

0

transcriptional regulation

up-regulates quantity by expression

0.429

CAMTA1 itself stimulates the expression of the anti-proliferative peptide NPPA.

SIGNOR-261570

P16871

P13232

2

binding

up-regulates

0.914

This receptor (il-7r) is a heterodimer consisting of the il-7r chain and the common cytokine ? -chain.

SIGNOR-163548

Q6ZMZ3

Q9H3D4

0

transcriptional regulation

up-regulates quantity by expression

0.2

Here we show that in the developing skin, epidermal progenitor cells of mice lacking p63 transcription factor display alterations in the nuclear shape accompanied by a marked decrease in expression of several nuclear envelope-associated components (Lamin B1, Lamin A/C, Sun1, Nesprin-3, Plectin) compared with controls. Furthermore, chromatin immunoprecipitation-quantitative PCR assay showed enrichment of p63 on Sun1, Syne3, and Plec promoters, suggesting them as p63 targets.

SIGNOR-263280

Q13571

P46934

0

ubiquitination

up-regulates activity

0.476

These results suggest that LAPTM5 ubiquitination is mediated by Nedd4.|Thus, Nedd4 promotes the recruitment of GGA3 to LAPTM5, allowing LAPTM5 translocation from the Golgi to the lysosome with the aid of GGA3.

SIGNOR-278768

Q15628

Q13546

2

binding

up-regulates activity

0.937

We show that tradd interacts strongly with rip;rip is a serinethreonine kinase that is recruited by tradd to tnfr1 in a tnf-dependent process.

SIGNOR-40043

P43026

Q9UHF7

1

relocalization

up-regulates activity

0.306

Treatment of cells with Gdf5 enhanced Trps1 protein levels and phosphorylation of p38 mitogen-activated protein kinase (MAPK) in a dose-dependent manner. Nuclear translocation of Trps1 was also induced by Gdf5. These effects were blocked by a dominant negative form of activin-linked kinase 6 (dn-Alk6) and by SB203580, an inhibitor of the p38 MAPK pathway. Conversely, Gdf5 expression was suppressed by the over-expression of Trps1.

SIGNOR-251867

Q96GD4

Q9H0H5

1

phosphorylation

up-regulates activity

0.78

It was found that the 5A fragment in which five Ser/Thr residues were substituted with Ala (S144A/T145A/S185A/T186A/S187A) fully prevented phosphorylation (Fig. 5B), confirming that Aurora B primarily phosphorylates five Ser/Thr residues in the basic region of MgcRacGAP. | the strong phosphorylation of the basic region of MgcRacGAP by Aurora B kinase was demonstrated, and this phosphorylation prevents the inhibition of MgcRacGAP GAP activity by PRC1

SIGNOR-250590

Q12959

Q9UQM7

0

phosphorylation

down-regulates activity

0.649

Synapse-associated protein 97 (SAP97), a member of membrane-associated guanylate kinase protein family, has been implicated in the processes of targeting ionotropic glutamate receptors at postsynaptic sites. | We show here that SAP97 is directly associated with NR2A through its PDZ1 domain, and CaMKII-dependent phosphorylation of SAP97-Ser-232 disrupts NR2A interaction both in an in vitro pull-out assay and in transfected COS-7 cells. Moreover, expression of SAP97(S232D) mutant has effects similar to those observed upon constitutively activating CaMKII.

SIGNOR-250618

P08047

P07288

1

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-253664

O95352

Q9BXW4

2

binding

up-regulates activity

0.789

Lc3-i is activated by the same atg7 involved in atg12 conjugation, transferred to atg3, a second e2-like enzyme, and finally conjugated to pe

SIGNOR-191540

Q01970

P41279

0

phosphorylation

up-regulates activity

0.2

Additionally, we found that PAR1-induced Ca2+ signals are transduced through Tpl2, which activates phospholipase C\u03b23 by phosphorylation at Ser537.|These findings raised the question whether Tpl2, which phosphorylates PLCbeta 3 at Ser537 (this report) regulates Ca 2+ signaling in thrombin stimulated cells through phosphorylation of PLCbeta 3 at this site.

SIGNOR-278519

Q13043

Q9UL54

0

phosphorylation

up-regulates

0.279

In addition, the thousand-and-one (tao) amino acids kinase or taok1 3 has been shown to directly phosphorylate and activate hpo or mst1/2

SIGNOR-201330

O95837

Q99500

2

binding

up-regulates activity

0.385

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-257437

P10636

Q9UM73

0

phosphorylation

up-regulates quantity

0.2

All these results point to the critical role played by ALK in the phosphorylation and accumulation of tau and in the associated memory impairment seen in 3xTg-AD mice.

SIGNOR-279318

Q92547

O95071

0

polyubiquitination

down-regulates quantity by destabilization

0.462

Using an in vitro reconstitution, specific E2 (ubiquitin-conjugating) enzymes (human UbcH4, UbcH5B, and UbcH5C) transferred ubiquitin molecules to hHYD, leading to the ubiquitination of TopBP1. TopBP1 was usually ubiquitinated and degraded by the proteosome, whereas X-irradiation diminished the ubiquitination of TopBP1 probably via the phosphorylation, resulting in the stable colocalization of up-regulated TopBP1 with gamma-H2AX nuclear foci in DNA breaks.

SIGNOR-272667

Q8TEW0

O14965

0

phosphorylation

up-regulates

0.35

Aurora a interacts directly with the atypical protein kinase c binding domain of par3 and phosphorylates it at serine 962. The phosphorylation of par3 at serine 962 contributes to its function in the establishment of neuronal polarity.

SIGNOR-188398

Q15077

P19086

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-257189

O60260

Q9NX47

0

ubiquitination

down-regulates quantity by destabilization

0.2

MITOL promotes cell survival by degrading Parkin during mitophagy.|Mechanistically, MITOL mediates ubiquitination of Parkin at lysine 220 residue, which promotes its proteasomal degradation, and thereby fine-tunes mitophagy by controlling the quantity of Parkin.

SIGNOR-278554

P17480

Q8IWS0

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

Q92890

Q9UKV5

2

binding

up-regulates activity

0.2

Here we show that Ufd1 directly interacts with gp78 and functions as a cofactor. Ufd1 enhances the E3 activity of gp78, accelerates the ubiquitination and degradation of reductase, and eventually promotes receptor-mediated uptake of low-density lipoprotein.

SIGNOR-252425

P27448

Q8IVT5

1

phosphorylation

down-regulates activity

0.642

C-TAK1 phosphorylates KSR1 at S392, forming a 14-3-3 binding site.|In mammalian cells, C-TAK1 has been shown to negatively regulate KSR1 by phosphorylation of Ser392.

SIGNOR-279225

P01019

P00797

2

binding

up-regulates activity

0.928

Renin is an aspartic protease that enzymatically cleaves its substrate angiotensinogen, which is produced by the liver, to form an inactive peptide: angiotensin (Ang)I or Ang (1–10).

SIGNOR-260224

Q5JTV8

P08670

2

binding

up-regulates activity

0.2

Co-immune precipitation studies revealed association between vimentin and torsinA in a complex. these studies suggest that mutant torsinA interferes with cytoskeletal events involving vimentin, possibly by restricting movement of these particles/filaments, and hence may affect development of neuronal pathways in the brain.

SIGNOR-261313

P12931

Q13002

1

phosphorylation

up-regulates activity

0.372

GluK2 binds to Src, and the tyrosine residue at position 590 (Y590) on GluK2 is a major site of phosphorylation by Src kinases. GluK2 phosphorylation at Y590 is responsible for increases in whole-cell currents and calcium influx in response to transient kainate stimulation.

SIGNOR-276850

Q13131

Q13554

0

phosphorylation

up-regulates

0.2

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

SIGNOR-138360

P24864

P49841

0

phosphorylation

down-regulates

0.445

Our experiments suggest that gsk3 is the kinase primarily responsible for phosphorylation of cyclin e on t380

SIGNOR-118563

Q16236

P13640

1

transcriptional regulation

up-regulates quantity by expression

0.286

NFE2L2 is stabilized and translocates to the nucleus, where it dimerizes with sMAF proteins. This complex binds to AREs to mediate the transcription of genes involved in iron metabolism, GSH metabolism, and ROS detoxification. The expression of MT1G during ferroptosis is regulated by the NFE2L2 signaling pathway. In the context of cancer, particularly HCC, the upregulation of MT1G has been linked to resistance against sorafenib, a kinase inhibitor commonly used in cancer therapy

SIGNOR-279866

Q93009

Q96EP1

1

deubiquitination

up-regulates quantity by stabilization

0.432

In this study, we identified USP7 (also known as HAUSP), which is a member of a family of proteins that cleave polyubiquitin chains and/or ubiquitin precursors, as an interacting protein with Chfr by immunoaffinity purification and mass spectrometry, and their interaction greatly increases the stability of Chfr. In fact, USP7 can remove ubiquitin moiety from the autoubiquitinated Chfr both in vivo and in vitro, which results in the accumulation of Chfr in the cell. USP7 mediates deubiquitination of Chfr.

SIGNOR-271462

O15392

Q96GD4

0

phosphorylation

down-regulates

0.795

Phosphorylation by aurora-b negatively regulates survivin function . hat survivin is phosphorylated at t117 during mitosis, and once phosphorylated, dephosphorylation is crucial for chromosome congression and progression into anaphaseduring mitosis

SIGNOR-154569

Q8TEL6

P01106

2

binding

down-regulates quantity by destabilization

0.35

We characterize a new Myc-interacting factor, TRPC4AP (transient receptor potential cation channel, subfamily C, member 4-associated protein)/TRUSS (tumor necrosis factor receptor-associated ubiquitous scaffolding and signaling protein), which is the receptor for a DDB1 (damage-specific DNA-binding protein 1)-CUL4 (Cullin 4) E3 ligase complex for selective Myc degradation through the proteasome. TRPC4AP/TRUSS binds specifically to the Myc C terminus and promotes its ubiquitination and destruction through the recognition of evolutionarily conserved domains in the Myc N terminus.

SIGNOR-271963

Q7Z589

P51587

2

binding

down-regulates activity

0.2

The EMSY protein interacts precisely with a highly conserved transactivating region at the N terminus of the breast cancer protein BRCA2, and has endogenous transcriptional repressor activity when recruited to a high basal promoter. We have suggested that the independent activation domain of BRCA2 within exon 3 might have some role in transcription (Milner et al., 1997). The identification of the repressor protein EMSY, which binds and silences this domain, is consistent with such a function.

SIGNOR-263915

P28069

P78337

2

binding

up-regulates activity

0.471

A novel OTX-related homeodomain transcription factor has been identified on the basis of its ability to interact with the transactivation domain of the pituitary-specific POU domain protein, Pit-1. P-OTX is able to independently activate and to synergize with Pit-1 on pituitary-specific target gene promoters.

SIGNOR-219740

P51812

P28482

0

phosphorylation

up-regulates

0.728

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

SIGNOR-161518

O75914

Q99523

1

phosphorylation

down-regulates activity

0.2

PAKs specifically phosphorylate Ser15 of the sortilin-cd and alter its trafficking. It can be concluded that PAK1-3 may indeed instigate the phosphorylation of sortilin and that they target a single serine residue (Ser15) located in the kinase domain-binding site of the sortilin-cd. Full-length sortilins with the serine at position 793 (residue 15 in the cytoplasmic domain) (for the sequence, see Fig. 2). Phosphorylation (Ser15) downregulates the sortilin–AP-1 interaction.

SIGNOR-273719

Q9UHD2

Q9BRV8

1

phosphorylation

down-regulates quantity

0.718

Mechanism of endogenous regulation of the type I interferon response by suppressor of I\u03baB kinase epsilon (SIKE), a novel substrate of TANK-binding kinase 1 (TBK1).|TBK1 phosphorylation of IRF3 and SIKE displayed negative cooperativity.

SIGNOR-280152

P53355

P28482

2

binding

down-regulates

0.565

Conversely, dapk promotes the cytoplasmic retention of erk, thereby inhibiting erk signaling in the nucleus.

SIGNOR-132610

P15514

P78536

0

cleavage

up-regulates activity

0.448

ADAM17 is involved in the release and activation of several growth factors and cytokine receptor ligands. Among the growth factors activated by ADAM17 are TGF-alpha, amphiregulin, epiregulin and HB-EGF

SIGNOR-259842

P54829

P42262

1

dephosphorylation

down-regulates activity

0.412

One study showed that stimulation of the metabotrophic glutamate receptor mGluR5 leads to a STEP mediated tyrosine dephosphorylation of GluA2 and internalization of GluA1 and GluA2, although the tyrosine residue on GluA2 that is dephosphorylated by STEP remains unidentified.

SIGNOR-277040

Q07869

P27361

0

phosphorylation

up-regulates activity

0.601

We now demonstrate that amino acids 1-92 of hPPARalpha contain an activation function (AF)-1-like domain, which is further activated by insulin through a pathway involving the mitogen-activated protein kinases p42 and p44. Further analysis of the amino-terminal region of PPARalpha revealed that the insulin-induced trans-activation occurs through the phosphorylation of two mitogen-activated protein kinase sites at positions 12 and 21, both of which are conserved across evolution.

SIGNOR-249474

O75581

O00744

2

binding

up-regulates activity

0.609

Wnt proteins bind to the frizzled receptors and lrp5/6 co-receptors, and through stabilizing the critical mediator betBeta-catenin, initiate a complex signaling cascade that plays an important role in regulating cell proliferation and differentiation.

SIGNOR-131631

Q15327

Q7Z570

0

transcriptional regulation

up-regulates quantity by expression

0.2

ZNF804A has been implicated in susceptibility to schizophrenia by several genome-wide association studies (GWAS), follow-up association studies and meta-analyses. ZNF804A was identified as a schizophrenia-associated gene by GWAS and was predicted to play a role in DNA binding and transcription To identify the genes that are affected by ZNF804A, we manipulated the expression of the ZNF804A protein in HEK293 human embryonic kidney cell lines and performed a cDNA microarray analysis followed by qPCR. We found that ZNF804A-overexpression up-regulated four genes (ANKRD1, INHBE, PIK3AP1, and DDIT3) and down-regulated three genes (CLIC2, MGAM, and BIRC3).

SIGNOR-269461

A6NJZ7

Q9UJD0

2

binding

down-regulates activity

0.265

SH3 domains of RBPs interact with RIMs. The enhancement of depolarization-induced secretion in PC12 cells by fusion proteins that suppress the associations of RBPs with RIMs and α1 suggests that RBPs may repress RIMs, either directly or through associated proteins.

SIGNOR-264372

P01137

P36897

2

binding

up-regulates activity

0.846

TGFbeta signals are transmitted via a cell surface receptor complex consisting of the TGFbeta type I receptor (TbetaRI) and TGFbeta type II receptor (TbetaRII). To initiate signal transduction, TGFbeta binds to TbetaRII, which in turn recruits TbetaRI, leading to the formation of a tetrameric receptor complex.

SIGNOR-249548

Q01860

Q9Y243

0

phosphorylation

up-regulates quantity by stabilization

0.257

Here we show that in ECCs, Akt phosphorylated the master pluripotency factor Oct4 at threonine 235, and that the levels of phosphorylated Oct4 in ECCs correlated with resistance to apoptosis and tumorigenic potential. Phosphorylation of Oct4 increased its stability and facilitated its nuclear localization and its interaction with Sox2, which promoted the transcription of the core stemness genes POU5F1 and NANOG.

SIGNOR-242107

P84022

P05412

2

binding

down-regulates activity

0.75

These results indicate that interaction between Smad3 and c-Jun may repress Smad3 transcriptional activity.

SIGNOR-256284

O15393

P10275

0

transcriptional regulation

up-regulates quantity by expression

0.575

The prostate-specific TMPRSS2 gene, while upregulated by AR activity in luminal cells, is also transcribed in basal populations, confirming that AR acts as an expression modulator.

SIGNOR-253687

P43403

Q16539

2

phosphorylation

up-regulates activity

0.476

Lck, Fyn, and Zap70 activate p38 even in the absence of Tyr182 phosphorylation.p38 is a substrate for Fyn, Lck and Zap70.Thus, T cell Src family kinases and Zap70 activate p38 by phosphorylating Tyr323.

SIGNOR-276030

P61073

P14174

2

binding

up-regulates activity

0.371

We identify the chemokine receptors CXCR2 and CXCR4 as functional receptors for MIF [] By activating both CXCR2 and CXCR4, MIF displays chemokine-like functions and acts as a major regulator of inflammatory cell recruitment and atherogenesis.

SIGNOR-252062

Q00987

P67775

0

dephosphorylation

up-regulates activity

0.455

cyclin G also binds in vivo and in vitro to Mdm2 and markedly stimulates the ability of PP2A to dephosphorylate Mdm2 at T216. Consistent with these data, cyclin G null cells have both Mdm2 that is hyperphosphorylated at T216 and markedly higher levels of p53 protein when compared to wild-type cells

SIGNOR-248636

P52333

P42229

1

phosphorylation

up-regulates

0.854

For these assays, coexpression of wt jak3 with stat5a was found to result in tyrosine phosphorylation of stat5a (lane 2) mediated by jak3, since stat5a coexpressed with the kinase-inactive k855a mutant form of jak3 was not tyrosine phosphorylated.

SIGNOR-182817

Q9NR19

Q14457

1

transcriptional regulation

up-regulates quantity by expression

0.2

As expected, we found that glucose deprivation induced the binding of TFEB (Figure S4C) and ACSS2 (Figure S4D) to the promoter regions of MAP1LC3B, ATG3, and WIPI-1 as well as mRNA (Figure 3H) and protein (Figure 3I) expression of these genes;

SIGNOR-276561

O75582

P84243

1

phosphorylation

down-regulates activity

0.2

Phosphorylation at ser-11 (h3s10ph) by rps6ka4 and rps6ka5 is important during interphase because it enables the transcription of genes following external stimulation, like mitogens, stress, growth factors or uv irradiation and result in the activation of genes, such as c-fos and c-jun.

SIGNOR-119233

Q02763

P35590

1

phosphorylation

up-regulates activity

0.348

Thus, Tie2 was able to induce Tie1 phosphorylation.|When cotransfected, Tie2 formed heteromeric complexes with Tie1, enhanced Tie1 activation, and induced phosphorylation of a kinase-inactive Tie1 in a ligand-dependent manner.

SIGNOR-279769

P11802

P05067

1

phosphorylation

down-regulates quantity by destabilization

0.258

These include a significant increase in APP phosphorylation at Thr 668 by cdk2, cdk4, and cdk5, which increases its beta-amyloid production and APP proteolysis by the activated caspases during cell cycle ( xref ; xref ; xref ; xref ).

SIGNOR-280214

Q96BA8

O43462

0

cleavage

up-regulates

0.568

Cleavage of oasis by site-1 and site-2 proteases / oasis is cleaved at the membrane under er stress conditions and that its cleaved n-terminal domain translocates into the nucleus;and then activates transcription of target genes

SIGNOR-143820

Q96GF1

O14641

1

polyubiquitination

down-regulates quantity by destabilization

0.466

The E3 ligase RNF185 negatively regulates osteogenic differentiation by targeting Dvl2 for degradation. Overexpression of RNF185 decreases the exogenous and endogenous level of Dvl2, promotes the ubiquitination and degradation of Dvl2

SIGNOR-272173

P33032

P63096

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-257070

P04626

2

phosphorylation

up-regulates

0.2

Stimulation of these molecules, however, failed to induce efficient cell migration in the absence of neu/erbb2 phosphorylation at tyr 1201 or tyr 1227

SIGNOR-124860

Q5T0W9

P48729

2

binding

up-regulates quantity

0.344

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-273746

P10451

P05186

0

dephosphorylation

down-regulates activity

0.442

This result suggests that endogenous mouse TNAP dephosphorylates OPN in osteoblasts and that overexpressed human TNAP dephosphorylates OPN, compensating for the lack of endogenous TNAP in [Col1a1-Tnap +/\u2212 ;Alpl \u2212/\u2212 ] cells.

SIGNOR-277045

P35222

Q06945

2

binding

up-regulates activity

0.592

We have demonstrated that Sox17 and Sox4 can directly interact with β-catenin and TCF/LEF proteins.Sox4 enhances β-catenin/TCF activity and the proliferation of SW480 cells.In contrast, Sox4 may function to stabilize β-catenin protein.

SIGNOR-256138

Q13547

P49715

1

transcriptional regulation

down-regulates

0.436

These data suggest that c/ebp beta activates a single unified pathway of adipogenesis involving its stimulation of ppargamma expression, which then activates c/ebp alpha expression by dislodging hdac1 from the promoter for degradation in the proteasome

SIGNOR-210013

Q12857

Q14393

1

transcriptional regulation

down-regulates quantity

0.2

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

SIGNOR-268876

P16298

O95644

1

relocalization

up-regulates

0.724

The ca2+ dependent phosphatase calcineurin induces cardiac and skeletal muscle hypertrophy by a process that involves nf-at nuclear translocation, and activation of mef2c.

SIGNOR-84047

P02708

O14905

2

binding

up-regulates

0.2

We identified five wnts (wnt9a, wnt9b, wnt10b, wnt11, and wnt16) that are able to stimulate achr clustering, of which wnt9a and wnt11 are expressed abundantly in developing muscles.

SIGNOR-195978

P84022

Q9GZU7

0

dephosphorylation

up-regulates activity

0.433

SCP1 Dephosphorylates Smad2/3 in the Linkers|MAPK-mediated linker phosphorylation appears to have a dual role in Smad2/3 regulation. Mitogens and hyperactive Ras result in extracellular signal-regulated kinase (ERK)-mediated phosphorylation of Smad3 at Ser-204, Ser-208, and Thr-179 and of Smad2 at Ser-245/250/255 and Thr-220. Mutation of these sites increases the ability of Smad3 to activate target genes, suggesting that MAPK phosphorylation of Smad3 is inhibitory (11, 12). However, in contrast, ERK-dependent phosphorylation of Smad2 at Thr-8 enhances its transcriptional activity

SIGNOR-248792

P11831

Q9ULH7

2

binding

up-regulates activity

0.2

MKL2 binds to and activates SRF similar to myocardin and MKL1.

SIGNOR-237671

Q14721

P23469

0

dephosphorylation

down-regulates activity

0.355

Hypomyelination and increased activity of voltage-gated K(+) channels in mice lacking protein tyrosine phosphatase epsilon

SIGNOR-248450

P14316

P33076

1

transcriptional regulation

up-regulates quantity by expression

0.525

In addition to IRF-1, IRF-2, another member of the IRF family, also activates the human CIITA type IV promoter, and IRF-2 cooperates with IRF-1 to activate the promoter in transient transfection assays.

SIGNOR-271681

P09619

P62993

2

binding

up-regulates

0.68

A pathway leading to activation of the gtp-binding protein ras involves the adaptor molecule grb2. Here we show that tyr-716, a novel autophosphorylation site in the pdgf beta-receptor kinase insert, mediates direct binding of grb2 in vitro and in vivo.

SIGNOR-34765

O00329

P21860

2

binding

up-regulates

0.416

Pi3k is the sole binding partner to six tyrosines of erbb3 and one in erbb4.

SIGNOR-146867

P68400

Q96NY9

1

phosphorylation

up-regulates activity

0.2

Here, we show that the CK2 kinase phosphorylates MUS81 at Serine 87 in late-G2/mitosis, and upon mild replication stress. Phosphorylated MUS81 interacts with SLX4, and this association promotes the function of the MUS81 complex.

SIGNOR-273626