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
Q70EL2	Q96EA4	1	deubiquitination	up-regulates activity	0.2	Spindly is mono-ubiquitylated and this ubiquitin can be removed by active USP45. K48 ubiquitylated complex that interacts with Spindly is also de-ubiquitylated by USP45. In the absence of USP45 catalytic activity, interaction is abolished and cell migration is affected similarly to the phenotype described for lack of Spindly.	SIGNOR-268505
Q14576	Q12955	1	post transcriptional regulation	down-regulates quantity	0.25	NElavl (composed of Elavl2, Elavl3, and Elavl4) proteins are the RNA-binding proteins that is specifically expressed in neurons, regulate the alternative splicing of target RNAs, and promote neuronal differentiation and maturation. Here, we found that the alternative splicing of AnkyrinG exon 34 was misregulated in the cerebella of Elavl3-/- mice. AnkyrinG is an essential factor for the formation of neuronal polarity and is required for normal neuronal functions.	SIGNOR-266861
Q14191	Q13535	0	phosphorylation	down-regulates quantity	0.794	Importantly, ATR-mediated phosphorylation targets Werner syndrome protein for ubiquitination and degradation.\|WRN is phosphorylated at serine 1141 by ATR in response to replication-associated DSBs A. WRN is heavily phosphorylated at S1141 in response to CPT treatment of cells.	SIGNOR-278159
O75367	Q8IWR1	0	polyubiquitination	down-regulates quantity by destabilization	0.2	Nuclear TRIM59 induces ubiquitination and degradation of the tumor suppressive histone variant macroH2A1, leading to enhanced STAT3 signaling activation and tumorigenicity.	SIGNOR-272931
P30679	Q9GZQ4	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-257352
Q92520	P42702	2	binding	up-regulates activity	0.2	Interleukin-like EMT inducer (ILEI) a cytokine from the FAM3 family, also functions as a ligand for LIFR-gp130 heterodimer and mediates intracellular signal through STAT activation.	SIGNOR-277986
P41235	P54646	0	phosphorylation	down-regulates quantity by destabilization	0.367	AMPK directly phosphorylates HNF4alpha and represses its transcriptional activity. AMPK-mediated phosphorylation of HNF4alpha on serine 304 had a 2-fold effect, reducing the ability of the transcription factor to form homodimers and bind DNA and increasing its degradation rate in vivo. Phosphorylation of HNF4α on Ser-304 reduces protein stability.	SIGNOR-250322
O95835	P06493	0	phosphorylation	up-regulates	0.389	Warts is a serine/threonine kinase and a dynamic component of the mitotic apparatus. We have found that cdc2/cyclin b forms a complex with a fraction of warts in the centrosome and phosphorylates the ser613 site of warts during mitosisit can be speculated that phosphorylation of warts by cdc2/cyclin b promotes a protein complex formation on the mitotic apparatus at early mitosis, which may be required for subsequent activation of warts kinase at the metaphase-anaphase transition.	SIGNOR-94160
O95136	P09471	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-257007
Q15797	Q8N4C8	0	phosphorylation	down-regulates activity	0.2	Msn kinases directly phosphorylate α-helix 1 of Smad. we have identified Misshapen (Msn) and the mammalian orthologs TNIK, MINK1, and MAP4K4 as the kinases responsible for α-helix 1 phosphorylation.	SIGNOR-276336
P23443	P06493	0	phosphorylation	up-regulates	0.384	Interestingly, phosphorylation at several ser/thr residues within the c-terminal autoinhibitory tail appears to either activate or inhibit s6k1, depending on the cell cycle phase. phosphorylation of those residues (featured by the thr-421/ser-424 site) during mitosis pursued by cdk1 inactivates s6k1 we then assessed the phosphorylation status of the mitosis-specific inhibitory residue of s6k1, thr-421/ser-424, which is targeted by mitotic cdk1.	SIGNOR-111507
Q9NXK8	Q14012	1	ubiquitination	down-regulates quantity	0.475	Here, we show that a ubiquitin E3 ligase component, F-box protein Fbxl12, mediates CaMKI degradation via a proteasome-directed pathway leading to disruption of cyclin D1/cdk4 complex. Endogenous Fbxl12 and CaMKI interacted as demonstrated after Fbxl12 immuno-precipitation followed by immunoblot analysis with CaMKI antibodies assembly and resultantG1 arrest in lung epithelia. Fbxl12 targets CaMKI for ubiquitination.	SIGNOR-261193
P19784	Q15022	1	phosphorylation	up-regulates activity	0.2	CK2 is the kinase for the phosphorylation of S583 of SUZ12.	SIGNOR-277797
O00444	Q15154	1	phosphorylation	up-regulates activity	0.573	Plk4‚Äêmediated phosphorylation of PCM1 at S372 is critical for the proper localisation of centriolar satellites, its dimer formation and interaction with other satellite components\|Therefore, Plk4 is responsible for PCM1 phosphorylation at S372.	SIGNOR-279556
Q9UMX1	Q8TBB1	0	ubiquitination	down-regulates quantity	0.2	Indeed, they target different lysine residues in the SuFu protein, as LNX1 ubiquitinates SuFu at K59 and K470, and SCF Fbxl17 acts at K257, while Itch ubiquitinates at K321 and K457.\|XREF_FIG, ectopic LNX1 expression reduced SuFu protein levels in HEK-293T cells, while shRNA mediated knockdown of LNX1 increased these levels.	SIGNOR-278626
O60260	Q00535	0	phosphorylation	down-regulates	0.2	Phosphorylation by cdk5 decreased the auto-ubiquitylation of parkin both in vitro and in vivo.	SIGNOR-153445
Q8IWR1	Q9BQ95	2	binding	down-regulates activity	0.518	In this study, we showed that one of the TRIM family ubiquitin ligases, TRIM59, interacts with ECSIT as an adaptor protein required for the TLR-mediated transduction pathway. The B-box and RING domains of TRIM59 are important for interaction with ECSIT.\|ECSIT enhances IPS-1-mediated IFN-Beta promoter activation.\|Luciferase reporter assays using reporter plasmids including NF-kappaB responsive element, interferon beta (IFN-beta) promoter and interferon-sensitive response element (ISRE) showed that overexpression of TRIM59 repressed their transcriptional activities, whereas knockdown of TRIM59 enhanced their transcriptional activities.	SIGNOR-260369
P51813	P25116	1	phosphorylation	down-regulates activity	0.2	As shown in xref \u2013 xref , BMX overexpression increased PAR1-WT phosphorylation but had no effect on PAR1 Y 381 FY 383 F mutant, indicating that BMX phosphorylated PAR1 at Y 381 and Y 383 .\|Mechanically , BMX represses PAR1 signaling in ECs by promoting PAR1 phosphorylation and internalization .	SIGNOR-279593
P78352	P12931	0	phosphorylation	up-regulates	0.565	These results indicate that psd-95 phosphorylation by src facilitates the integration of pyk2 to psd-95 signal complex, the activation of pyk2/src, as well as the subsequent tyrosine phosphorylation of nr2a, which ultimately results in the upregulation of nmda receptor function and synaptic transmission.	SIGNOR-205120
O96013	O96013	2	phosphorylation	up-regulates	0.2	Intracellular localization;enzymatic activity, induced;cell growth, altered;	SIGNOR-168301
P62837	O95071	1	ubiquitination	up-regulates activity	0.508	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-272668
P01137	P02452	1	transcriptional regulation	up-regulates quantity by expression	0.485	COL1A1 expression is regulated by upstream genes and the binding of regulatory elements at multiple binding sites upstream of its promoter. During cancer progression, CAFs reorganize and cross-link COL1A1, which accumulates and stiffens in the tumor stroma [12], [18]. This process may involve fibrogenic factors, especially transforming growth factor-beta (TGF-β1). Indeed, a TGF-β1 response sequence was identified 174 nucleotides upstream of the COL1A1 transcription start site, and was shown to up-regulate COL1A1 promoter activity	SIGNOR-277678
Q15139	Q05655	0	phosphorylation	up-regulates	0.269	Here we show that activation of pkd in response to oxidative stress requires two sequential signaling events, i.e., phosphorylation of tyr463 by abl, which in turn promotes a second step, phosphorylation of the pkd activation loop (ser738/ser742). We show that this is mediated by pkcdelta (protein kinase cdelta)	SIGNOR-123453
Q05655	P05107	1	phosphorylation	up-regulates	0.329	In this study, we present evidence that pkc isoforms are the major protein kinases that phosphorylate the c terminus of the integrin cd18 chain in leukocytes. Ser-745 is identified as a novel phosphorylation site in the integrin cytoplasmic domain. Additionally, we show that a thr-758-phosphorylated integrin peptide can interact with 14-3-3 proteins in leukocyte lysates	SIGNOR-178897
P25098	Q13304	1	phosphorylation	down-regulates activity	0.2	As depicted in Fig. 8 A and B, GRK2 silencing resulted in up-regulation of GPR17 and down-regulation of the mature markers CNPase and MBP, indicating a shift of cells toward a less differentiated stage.Having established that, in primary cultured OPCs, LTD 4 mediated desensitization of GPR17 through the primary recruitment of GRK2, we then asked whether GRK2 pharmacological inhibition had any effects on cysLT promoted cell maturation.\|These data demonstrate that LTD 4 -induced GPR17 phosphorylation is preferentially mediated by GRK2 and only partially by GRK5, whereas UDP-glucose-mediated receptor phosphorylation exclusively requires the GRK5 isoform.We examined the involvement of GRK2 and GRK5 in agonist induced desensitization of GPR17.	SIGNOR-279999
Q8NEZ5	P04637	1	ubiquitination	down-regulates quantity by destabilization	0.338	We demonstrate here that SCFFbxo22-KDM4A is a senescence-associated E3 ligase targeting methylated p53 for degradation. We find that Fbxo22 is highly expressed in senescent cells in a p53-dependent manner, and that SCFFbxo22 ubiquitylated p53 and formed a complex with a lysine demethylase, KDM4A. \|SCFFbxo22 forms a ternary complex with p53 and KDM4A that targets methylated p53 for degradation.	SIGNOR-273448
O43353	Q9Y4K3	2	binding	up-regulates activity	0.685	Binding of bacterial MDP or viral RNA to NOD2 results in the association of RIPK2 with TRAF6 and subsequent activation of TRAF6.	SIGNOR-280456
Q8TEW0	Q05513	0	phosphorylation	up-regulates	0.711	These results imply that serine 827 in the apkc binding site of par-3 is a target of apkc and that the regulated interaction between a protein kinase, apkc, and its substrate, par-3, plays an essential role in the establishment of cell polarity	SIGNOR-94523
O43791	P10070	1	ubiquitination	down-regulates quantity	0.71	RNAi knockdown of Spop (a substrate-binding adaptor for the cullin3-based ubiquitin E3 ligase) in Sufu mutant mouse embryonic fibroblasts (MEFs) can restore the levels of Gli2 and Gli3 full-length proteins	SIGNOR-268860
Q9NRM7	P17612	0	phosphorylation	up-regulates	0.2	Here, we show that cyclic amp (camp)-dependent protein kinase (pka) phosphorylates lats and thereby enhances its activity sufficiently to phosphorylate yap on ser381.	SIGNOR-236994
P62714	O14757	1	dephosphorylation	down-regulates activity	0.266	Phosphorylation of Chk1 by ATR is antagonized by a Chk1-regulated protein phosphatase 2A circuit\|In response to genotoxic stress, Chk1 is phosphorylated on serines 317 (S317) and 345 (S345) by the ataxia-telangiectasia-related (ATR) protein kinase. Phosphorylation of Chk1 on these C-terminal serine residues is used as an indicator of Chk1 activation in vivo.	SIGNOR-248578
Q07666	P06213	0	phosphorylation	up-regulates activity	0.363	Thus, Tyr phosphorylation of Sam68 by IR could modulate its association with the splicing machinery in a similar way to that described for p59 fyn, and this way, it could influence splice site selection.	SIGNOR-278946
P41743	P61019	2	binding	down-regulates activity	0.456	Rab2 Binds to the PKCι/λ Regulatory Domain and Inhibits PKCι/λ-dependent GAPDH Phosphorylation	SIGNOR-261301
P16949	Q8NG68	2	binding	down-regulates	0.389	Stathmin depresses ttl tubulin tyrosination activityin vitro.	SIGNOR-193465
Q9UBE8	P46531	1	phosphorylation	down-regulates	0.382	Nlk-phosphorylated notch1icd is impaired in its ability to form a transcriptionally_ active_ ternary_ complex.	SIGNOR-163697
Q8IUR6	Q15011	1	transcriptional regulation	up-regulates quantity by expression	0.2	Luman/CREB3 induces transcription of the endoplasmic reticulum (ER) stress response protein Herp through an ER stress response element.	SIGNOR-261575
O76050	O76083	1	polyubiquitination	down-regulates quantity by destabilization	0.2	Neuralized family member NEURL1 is a ubiquitin ligase for the cGMP-specific phosphodiesterase 9A. We also demonstrate that NEURL1 can promote polyubiquitination of PDE9A that leads to its proteasome-mediated degradation mainly via lysine residue K27 of ubiquitin.	SIGNOR-272305
Q13569	Q9NZJ0	2	binding	down-regulates quantity by destabilization	0.358	TDG Is Polyubiquitinated by CRL4Cdt2 E3 Ubiquitin Ligase in a PIP Degron-dependent Manner	SIGNOR-272847
P54727	P23025	2	binding	up-regulates activity	0.769	GG-NER is initiated by the GG-NER specific factor XPC-RAD23B, in some cases with the help of UV-DDB (UV-damaged DNA-binding protein). TC-NER is initiated by RNA polymerase stalled at a lesion with the help of TC-NER specific factors CSA, CSB, and XAB2. Both pathways require the core NER factors to complete the excision process\|The core NER dual incision reaction has been reconstituted in vitro with purified factors using XPC-RAD23B, TFIIH, XPA, RPA, XPG, and ERCC1-XPF (Aboussekhra et al. 1995; Mu et al. 1995; Araujo et al. 2000).\|The core NER dual incision reaction has been reconstituted in vitro with purified factors using XPC-RAD23B, TFIIH, XPA, RPA, XPG, and ERCC1-XPF (Aboussekhra et al. 1995; Mu et al. 1995; Araujo et al. 2000). Functional studies revealed that XPC-RAD23B is the initial damage recognition factor in this system, as the presence of XPC-RAD23B is required for assembly of the other core NER factors and progression through the NER pathway both in vitro and in vivo	SIGNOR-275697
O60216	P23769	1	relocalization	down-regulates activity	0.325	Large-scale AML genome re-sequencing efforts have identified novel recurrently mutated genes, including the members of the cohesin complex (RAD21, SMC3, SMC1A, and STAG2), implicated in the pathogenesis of this disease.Using ATAC-seq, we determined that mutant cohesin lead to a state of elevated chromatin accessibility and higher predicted binding at transcription factor binding sites for ERG, GATA2, and RUNX1. Moreover, using ChIP-Seq, we formally demonstrated increased binding of GATA2 and RUNX1 to these sites. Finally, we demonstrated that knockdown of these three TFs in human HSPC can revert the differentiation block induced by mutant cohesin. These results support a model in which mutant cohesin impairs hematopoietic differentiation and enforces stem cell programs through the modulation of ERG, GATA2, and RUNX1 chromatin accessibility, expression, and activity.	SIGNOR-261513
P27694	Q9UMS4	0	polyubiquitination	up-regulates activity	0.509	PRP19 is a ubiquitin ligase involved in pre-mRNA splicing and the DNA damage response (DDR). PRP19 ubiquitylates RPA and promotes ATRIP recruitment.	SIGNOR-272076
Q92783	O60674	0	phosphorylation	up-regulates	0.617	Stam is associated with jak3 and jak2 tyrosine kinases via its itam region and phosphorylated by jak3 and jak2 upon stimulation with il-2.	SIGNOR-47834
P19086	P48039	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-257101
Q14247	Q8WZ74	2	binding	up-regulates activity	0.511	Fluorescence recovery after photobleaching further suggested that CTTNBP2 modulates the mobility of cortactin in neurons. CTTNBP2 may thus help to immobilize cortactin in dendritic spines and control the density of dendritic spines.	SIGNOR-269703
Q969T4	P25963	1	sumoylation	up-regulates quantity by stabilization	0.346	In the presence of an E1 SUMO-1-activating enzyme, Ubch9 conjugated SUMO-1 to IkappaBalpha primarily on K21, which is also utilized for ubiquitin modification. Thus, SUMO-1-modified IkappaBalpha cannot be ubiquitinated and is resistant to proteasome-mediated degradation.	SIGNOR-270545
O43561	P45983	0	phosphorylation	down-regulates	0.308	Lat, an adapter protein essential for t-cell signaling, is phosphorylated at its thr 155 by erk in response to t-cell receptor stimulation. Thr 155 phosphorylation reduces the ability of lat to recruit plcgamma1 and slp76, leading to attenuation of subsequent downstream events such as [ca2+]i mobilization and activation of the erk pathway.Mutational analysis revealed that t155 but not t94 or t140 is the site of jnk-mediated phosphorylation (figure 2b). Erk also phosphorylated lat at t155 (figure 2c), whereas p38, which was able to phosphorylate atf2, failed to induce threonine phosphorylation of lat (figure 2d). These results indicate that lat is directly phosphorylated by erk and jnk at the same site, t155.	SIGNOR-125774
Q5JVS0	P05771	0	phosphorylation	down-regulates activity	0.29	We found a strong phosphorylation of Ki-1/57 by PKCalphabeta, PKCdelta, PKClambda/zeta, and especially by PKCsigma, however not by PKCmi. These data show that Ki-1/57 can serve in principal as a substrate for a wide variety of different PKC isoforms but also that its phosphorylation is strongest with PKCsigma. \| This suggests that the two threonine residues present in this fragment (Thr354 and Thr375) might be the main target residues for phosphorylation by PKC in vitro. \| Ki-1/57 Exits the Nucleus upon PMA Activation	SIGNOR-249247
P21399	P17252	0	phosphorylation	down-regulates	0.2	Irp1 ser-711 is a phosphorylation site, critical for regulation of rna-binding and aconitase activities.	SIGNOR-133188
P05112	P31785	2	binding	up-regulates	0.858	The common gamma-chain (gamma(c)) is an indispensable subunit of the functional receptor complexes for il-4, il-7, il-9, and il-15 as well as il-2. Here we show that the gamma(c) is also shared with the il-21r complex	SIGNOR-108861
P23771	P17676	2	binding	down-regulates	0.352	In the present study, we demonstrate that both gata-2 and gata-3 form protein complexes with ccaat/enhancer binding protein alpha (c/ebpalpha) and c/ebpbeta, members of a family of transcription factors that are integral to adipogenesis. []the interaction between gata and c/ebp factors is critical for the ability of gata to suppress adipocyte differentiation.	SIGNOR-132952
Q53EL6	Q9Y297	0	ubiquitination	down-regulates	0.425	Both akt and p70(s6k) phosphorylate pdcd4, allowing for binding of the e3-ubiquitin ligase beta-trcp and consequently ubiquitylation.	SIGNOR-160985
Q9UHD2	O00571	1	phosphorylation	up-regulates activity	0.721	Coexpression of TBK1 strongly increased the activity of DDX3X.\|This suggests that DDX3X is rather specifically phosphorylated by TBK1 and IKK-i.	SIGNOR-278997
P10415	Q86UR1	0	null	down-regulates activity	0.2	BH3-only proteins containing only a single BH domain and including Puma, Noxa, Bid and Bad as well as other factors are particularly important for such neutralisation, binding and regulating the anti-apoptotic Bcl-2 proteins to promote apoptosis	SIGNOR-209684
Q9Y613	Q13976	0	phosphorylation	up-regulates	0.354	Pkgi also directly phosphorylates fhod1, and studies with wild-type and mutant fhod1-derived peptides identify ser-1131 in the fhod1 c terminus as the unique pkgi phosphorylation site in fhod1. phosphorylation of three conserved residues within the dad domain activates fhod1 while binding to rac regulates fhod1 subcellular localization	SIGNOR-123646
Q13618	Q8N653	2	binding	up-regulates activity	0.273	Leucine zipper-like transcriptional regulator 1 (LZTR1) encodes a member of the BTB-Kelch superfamily, which interacts with the Cullin3 (CUL3)-based E3 ubiquitin ligase complex.	SIGNOR-269070
Q96EB6	P98177	1	deacetylation	up-regulates	0.744	Deacetylation of foxos involves binding of the nad-dependent deacetylase hsir2(sirt1). Accordingly, hsir2(sirt1)-mediated deacetylation precludes foxo inhibition through acetylation and thereby prolongs foxo-dependent transcription of stress-regulating genes.	SIGNOR-124714
P24928	Q9NP77	0	dephosphorylation	up-regulates activity	0.855	Phosphorylation of serine-2 (S2) and serine-5 (S5) of the C-terminal domain (CTD) of RNA polymerase II (RNAP II) is a dynamic process that regulates the transcription cycle and coordinates recruitment of RNA processing factors. The Fcp1 CTD phosphatase catalyzes dephosphorylation of S2-P.\| Depletion of Ssu72 impairs transcription in vitro	SIGNOR-248815
Q02750	P28482	2	phosphorylation	up-regulates activity	0.75	Mapk1 is phosphorylated by map2k1/mek1 and map2k2/mek2 on thr-185 and tyr-187 in response to external stimuli like insulin or ngf. Both phosphorylations are required for activity.	SIGNOR-236447
P17676	Q8N695	1	transcriptional regulation	up-regulates quantity by expression	0.2	Luciferase reporter assays of deletion mutants of SLC5A8 promoter demonstrated that a 295-bp region is essential for the basal promoter activity of the SLC5A8 gene. Further analysis indicated that the CCAAT boxes and GC boxes were involved in positive regulation of SLC5A8 promoter. Overexpression of two transcription factors, CCAAT/enhancer binding protein beta (C/EBPbeta) and specific transcription factor 1 (Sp1), upregulated the activities of the human SLC5A8 promoter and protein expression, suggesting that both C/EBPbeta and Sp1 transcription factors might have functions in SLC5A8 transcription.	SIGNOR-254054
Q99677	P63092	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 ‚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-256785
P47900	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-256943
P06241	Q16539	1	phosphorylation	up-regulates	0.489	T cell src family kinases and zap70 activate p38 by phosphorylating tyr323.	SIGNOR-134293
P30989	P34947	0	phosphorylation	up-regulates activity	0.594	Here we report the unique phosphorylation\nof NTSR1 by GRK2 and GRK5, which belong to the GRK2 and GRK4 subfamilies,\nrespectively.	SIGNOR-278234
P19838	P04150	0	transcriptional regulation	down-regulates quantity by repression	0.6	We have described how the receptor uses several means to achieve repression of the genes regulated by AP-1 and NF-KB proteins	SIGNOR-251680
P00519	P29350	1	phosphorylation	up-regulates activity	0.414	The results demonstrate that the SH3 domain of ABL1 interacts with a WPDHGVPSEP motif (residues 417-426) in the catalytic domain of SHPTP1 and that ABL1 phosphorylates C terminal Y536 and Y564 sites.	SIGNOR-260820
P67775	P35222	1	dephosphorylation	up-regulates	0.462	In the absence of the wt apc protein, phosphorylated beta-catenin is rapidly dephosphorylated by serine/threonine protein phosphatase 2a (pp2a). phosphorylated beta-catenin associated with the wild-type apc protein is recruited to the scf(beta-trcp) complex, ubiquitin conjugated, and degraded.	SIGNOR-182637
P55036	Q05086	0	polyubiquitination	down-regulates quantity by destabilization	0.463	S5a/Rpn10 is a ubiquitin (Ub)-binding protein that is a subunit of the 26S proteasome but also exists free in the cytosol. It binds poly-Ub chains through its two Ub-interacting motifs (UIMs). We discovered that, unlike typical substrates of Ub ligases (E3s), S5a can be ubiquitinated by all E3s tested including multimeric and monomeric Ring finger E3s (MuRF1, Siah2, Parkin, APC, and SCF(betaTRCP1)), the U-box E3, CHIP, and HECT domain E3s (E6AP and Nedd4) when assayed with UbcH5 or related Ub-conjugating enzymes.The short half-life of S5a presumably is because of the presence of the UIM domain and reflects the ubiquitination of free S5a by many E3s. Surprisingly, the same four Lys residues on S5a, Lys-74, Lys-122, Lys-262, and Lys-365 were ubiquitinated by MuRF1 and E6AP (Fig. 10). Two additional Lys residues (Lys-126 and -135) were ubiquitinated by E6AP.	SIGNOR-272746
O14640	O75084	2	binding	up-regulates	0.661	In non-canonical Wnt signalling, Wnt proteins bind Fzd and glypican-4, to activate Dsh at the cell membrane, leading to activation of Rho and JNK	SIGNOR-255893
O43251	O14920	0	phosphorylation	up-regulates activity	0.2	Phosphorylation of RTA by IKKbeta increases RTA transcriptional activity and consequently viral mRNA production.	SIGNOR-279336
Q15121	P31749	0	phosphorylation	up-regulates activity	0.517	Protein kinase b/akt binds and phosphorylates ped/pea-15, stabilizing its antiapoptotic action.	SIGNOR-102092
Q13651	P22301	2	binding	up-regulates	0.914	Functionally active il-10 receptors are composed of two distinct subunits. The il-10 receptor ? Chain is a 110-kda polypeptide that plays the dominant role in mediating high affinity ligand binding and signal transduction. The il-10 receptor ? Subunit (also known as crf2_4) is predicted to be a 40-kda polypeptide that is largely required only for signaling	SIGNOR-67964
P08754	P35346	2	binding	up-regulates activity	0.45	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-256833
P06744	Q9UKV5	2	binding	up-regulates	0.53	Pgi is a housekeeping gene encoding phosphoglucose isomerase (pgi) a glycolytic enzyme that also functions as a cytokine (autocrine motility factor (amf)/neuroleukin/maturation factor) upon secretion from the cell and binding to its 78 kda seven-transmembrane domain receptor (gp78/amf-r)	SIGNOR-97270
Q00535	Q05397	1	phosphorylation	up-regulates	0.305	Here, we show that fak phosphorylation by cdk5 at s732 is important for microtubule organization, nuclear movement, and neuronal migration. In cultured neurons, s732-phosphorylated fak is enriched along a centrosome-associated microtubule fork that abuts the nucleus. Overexpression of the nonphosphorylatable mutant fak s732a results in disorganization of the microtubule fork and impairment of nuclear movement in vitro, and neuronal positioning defects in vivo.	SIGNOR-86223
P49757	Q00987	2	binding	down-regulates	0.444	Numb interacts with mdm2, and inhibits its ubiquitin-ligase function on tp53 (which in itself is inhibitory for tp53), thus numb activates (b) tp53	SIGNOR-168454
P20807	P49840	1	cleavage	up-regulates activity	0.2	Thus, it has been shown that calpain cleaves the inhibitory domain of GSK3 generating two fragments of 40 and 30 kDa. This cleavage enhanced activity of the kinase	SIGNOR-251606
P30411	P25098	0	phosphorylation	down-regulates activity	0.2	Ligand-induced phosphorylation is found at Ser339 and Ser346/Ser348 that could be executed by several G protein-coupled receptor kinases. 32P labeling of peptide 3 containing pS346/pS348 was enhanced 1.5–3-fold as compared with mock-transfected cells in the order GRK6 < GRK5 < GRK2 < GRK4α < GRK3. several endogenous GRKs may phosphorylate the B2R and that the various GRKs, even without apparent effect on total GPCR phosphorylation levels, may induce distinct phosphorylation patterns with possible functional consequences for receptor desensitization and sequestration.	SIGNOR-251445
P36894	P12643	2	binding	up-regulates	0.929	BMP interacts with specific receptors on the cell surface, BMP receptor types 1 and 2 (BMPr1 and BMPr2).	SIGNOR-253547
P21127	Q07955	1	phosphorylation	up-regulates activity	0.283	In comparison, CLK1 expression leads to speckle dissolution and diffuse GFP-SRSF1 localization in the nucleus.\|We showed that CLK1 phosphorylates SRSF1 at approximately 18 sites inducing a gel shift from 35 to about 38 kDa on SDS-PAGE (XREF_FIG, upper panel).	SIGNOR-279499
Q13535	Q8N163	1	phosphorylation	up-regulates activity	0.438	Here, we report that, in human cell lines, DNA damage triggered the phosphorylation of DBC1 on Thr454 by ATM (ataxia telangiectasia-mutated) and ATR (ataxia telangiectasia and Rad3-related) kinases. Phosphorylated DBC1 bound to and inhibited SIRT1, resulting in the dissociation of the SIRT1-p53 complex and stimulating p53 acetylation and p53-dependent cell death.	SIGNOR-267662
O00141	P28482	1	phosphorylation	up-regulates activity	0.309	SGK1 was found to physically interact with ERK1/2 as well as MEK1/2. Furthermore, SGK1 mediated the phosphorylation of ERK2 on Ser(29) in a serum-dependent manner. Replacement of Ser(29) to aspartic acid, which mimics the phosphorylation of Ser(29), enhanced the ERK2 activity as well as the MEK/ERK complexes formation.	SIGNOR-276223
P19174	P35968	2	binding	up-regulates	0.675	(vegfr) phosphorylated y1175 creates a binding site for phospholipase cgamma1 (plc-gamma1)	SIGNOR-147870
Q08828	P63092	2	binding	up-regulates activity	0.627	Because adenylyl cyclases are directly activated by G(s)alpha and the carboxyl termini of the various Galpha proteins determine their receptor coupling specificity, we proposed a set of chimeric G(s)alpha where the COOH-terminal five amino acids are replaced by those of other Galpha proteins and used these to dissect the potential Galpha linked to a given GPCR	SIGNOR-156958
Q13627	P13807	1	phosphorylation	down-regulates activity	0.267	DYRK Family Protein Kinases Phosphorylate and Inactivate Glycogen Synthase. both protein kinases phosphorylate site 3a but no other sites that affect glycogen synthase activity.	SIGNOR-260632
P38936	O43293	0	phosphorylation	up-regulates quantity by stabilization	0.316	ZIP kinase phosphorylates p21(WAF1) at Thr145 and alanine-substituted mutations in the p21(WAF1) phosphorylation site alter its ability to be phosphorylated by ZIP kinase. \| Transfected ZIPK can promote the phosphorylation of p21(WAF1) at Thr145 in vivo and can increase the half-life of p21(WAF1)	SIGNOR-251085
P05112	O95644	0	transcriptional regulation	up-regulates quantity by expression	0.549	Recombinant NFAT1 can mediate transcription of the interleukin-2, interleukin-4, tumor necrosis factor alpha, and granulocyte-macrophage colony-stimulating factor promoters in T cells, suggesting that NFAT1 contributes to the CsA-sensitive transcription of these genes during the immune response.	SIGNOR-254498
P06239	P07766	1	phosphorylation	up-regulates activity	0.692	Tyrosine Phosphorylation of CD8- Chimeras by Lck and ZAP-70 in COS Cells. both Y170F and Y181F chimeric proteins could be efficiently phosphorylated by Lck in vivo. phosphorylation of Y170 and Y181 within CD3- –ITAM provides to CD3- the potential to interact with multiple downstream effectors and signaling pathways.	SIGNOR-251369
Q92949	P48380	2	binding	up-regulates activity	0.548	RFX3 acts as a transcriptional co-activator to FOXJ1 that enhances the expression of cilia-associated genes. FOXJ1 is an important regulator of cilia gene expression during ciliated cell differentiation, with RFX3 as a transcriptional co-activator to FOXJ1, helping to induce the expression of cilia genes in the process of ciliated cell differentiation of basal/progenitor cells.	SIGNOR-266929
Q8WU20	P04629	2	binding	up-regulates	0.779	The signaling adapter frs-2 competes with shc for binding to the nerve growth factor receptor trka:a model for discriminating proliferation and differentiation	SIGNOR-65955
Q13153	P16333	2	binding	up-regulates activity	0.709	Both nck and grb4 proteins could associate with receptor tyrosine kinases and the sh3-binding proteins pak, sos1, and prk2, and they synergized with v-abl and sos to induce gene expression via the transcription factor elk-1. Association of nck with pak1 may serve to link this important regulatory kinase to cell activation by growth factor receptors.	SIGNOR-236512
Q5TZA2	Q96CN5	2	binding	up-regulates activity	0.44	Here, we show that LRRC45 is a centrosome linker that localizes at the proximal ends of the centrioles and forms fiber-like structures between them. Depletion of LRRC45 results in centrosome splitting during interphase. LRRC45 interacts with C-Nap1 and rootletin	SIGNOR-273704
O43318	Q12933	0	ubiquitination	up-regulates activity	0.597	Tumor necrosis factor receptor-associated factors 2 and 6 (traf2 and -6) act as the ubiquitin e3 ligases to mediate lys63-linked tak1 polyubiquitination at the lys158 residue in vivo and in vitro. Lys(63)-linked TAK1 polyubiquitination at the Lys(158) residue is required for TAK1-mediated IKK complex recruitment.	SIGNOR-162638
Q96GX5	Q96GX5	2	phosphorylation	up-regulates activity	0.2	After this priming step, Gwl can intramolecularly phosphorylate its C-terminal tail at pS883; this site probably plays a role similar to that of the tail/Z motif of other AGC kinases.	SIGNOR-243409
O43683	Q8NG31	2	binding	up-regulates	0.2	Association of the amino and middle domain of blinkin with the tpr domains in the amino termini of bubr1 and bub1 is essential for bubr1 and bub1 to execute their distinct mitotic functions	SIGNOR-158378
Q9UGL1	O94992	0	relocalization	up-regulates activity	0.2	We previously reported that the tumor suppressor HEXIM1 is a mediator of KDM5B recruitment to its target genes, and HEXIM1 is required for the inhibition of nuclear hormone receptor activity by KDM5B.	SIGNOR-273439
P31749	P23769	1	phosphorylation	down-regulates	0.524	We show that insulin induces gata2 phosphorylation on serine 401 in a pi-3k/akt-dependent manner. Insulin-dependent phosphorylation of serine 401 impairs gata2 translocation to the nucleus and its dna binding activity	SIGNOR-135614
P45985	P45984	1	phosphorylation	up-regulates	0.729	Mkk4, which activates p38gamma, p38delta, and jnk2 to phosphorylate p53 on ser-33 and cause a transient g(1) arrest. A map kinase kinase kinase (mapkkk), termed ask1, was identified that activated two different subs of map kinase kinases (mapkk), sek1 (or mkk4) and mkk3/mapkk6 (or mkk6), which in turn activated stress-activated protein kinase (sapk, also known as jnk;c-jun amino-terminal kinase) here we report that mkk4 shows a striking preference for the tyrosine residue (tyr-185), and mkk7 a striking preference for the threonine residue (thr-183) in three sapk1/jnk1 isoforms tested (jnk1 alpha 1, jnk2 alpha 2 and jnk3 alpha 1)	SIGNOR-197998
P11309	P42229	0	transcriptional regulation	up-regulates quantity by expression	0.375	The results of 2 microarray experiments demonstrated that the aberrant activation of STAT proteins by Flt3-ITDs resulted in the up-regulation of several STAT5-responsive genes, such as Pim-1, Pim-2, and members of the SOCS (suppressor of cytokine signaling) protein family. These results are particularly interesting because recent data point to an important role of Pim kinases in the antiapoptosis of hematopoietic cells.	SIGNOR-249621
Q8TEK3	P01106	2	binding	up-regulates activity	0.334	Our data suggest that the c-Myc-dependent transcriptional switch is modulated by DOT1L, as in the presence of DOT1L c-Myc preferentially forms an active complex with p300 rather than a repressive complex containing HDAC1 and DNMT1	SIGNOR-239362
P55347	P14653	2	binding	up-regulates activity	0.613	we observe the formation of a ternary Prep1-Pbx1-HOXB1 complex on a HOXB1-responsive target in vitro. Interaction with Prep1 enhances the ability of the HOXB1-Pbx1 complex to activate transcription in a cooperative fashion from the same target.	SIGNOR-241215

Q70EL2

Q96EA4

1

deubiquitination

up-regulates activity

0.2

Spindly is mono-ubiquitylated and this ubiquitin can be removed by active USP45. K48 ubiquitylated complex that interacts with Spindly is also de-ubiquitylated by USP45. In the absence of USP45 catalytic activity, interaction is abolished and cell migration is affected similarly to the phenotype described for lack of Spindly.

SIGNOR-268505

Q14576

Q12955

1

post transcriptional regulation

down-regulates quantity

0.25

NElavl (composed of Elavl2, Elavl3, and Elavl4) proteins are the RNA-binding proteins that is specifically expressed in neurons, regulate the alternative splicing of target RNAs, and promote neuronal differentiation and maturation. Here, we found that the alternative splicing of AnkyrinG exon 34 was misregulated in the cerebella of Elavl3-/- mice. AnkyrinG is an essential factor for the formation of neuronal polarity and is required for normal neuronal functions.

SIGNOR-266861

Q14191

Q13535

0

phosphorylation

down-regulates quantity

0.794

Importantly, ATR-mediated phosphorylation targets Werner syndrome protein for ubiquitination and degradation.|WRN is phosphorylated at serine 1141 by ATR in response to replication-associated DSBs A. WRN is heavily phosphorylated at S1141 in response to CPT treatment of cells.

SIGNOR-278159

O75367

Q8IWR1

0

polyubiquitination

down-regulates quantity by destabilization

0.2

Nuclear TRIM59 induces ubiquitination and degradation of the tumor suppressive histone variant macroH2A1, leading to enhanced STAT3 signaling activation and tumorigenicity.

SIGNOR-272931

P30679

Q9GZQ4

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-257352

Q92520

P42702

2

binding

up-regulates activity

0.2

Interleukin-like EMT inducer (ILEI) a cytokine from the FAM3 family, also functions as a ligand for LIFR-gp130 heterodimer and mediates intracellular signal through STAT activation.

SIGNOR-277986

P41235

P54646

0

phosphorylation

down-regulates quantity by destabilization

0.367

AMPK directly phosphorylates HNF4alpha and represses its transcriptional activity. AMPK-mediated phosphorylation of HNF4alpha on serine 304 had a 2-fold effect, reducing the ability of the transcription factor to form homodimers and bind DNA and increasing its degradation rate in vivo. Phosphorylation of HNF4α on Ser-304 reduces protein stability.

SIGNOR-250322

O95835

P06493

0

phosphorylation

up-regulates

0.389

Warts is a serine/threonine kinase and a dynamic component of the mitotic apparatus. We have found that cdc2/cyclin b forms a complex with a fraction of warts in the centrosome and phosphorylates the ser613 site of warts during mitosisit can be speculated that phosphorylation of warts by cdc2/cyclin b promotes a protein complex formation on the mitotic apparatus at early mitosis, which may be required for subsequent activation of warts kinase at the metaphase-anaphase transition.

SIGNOR-94160

O95136

P09471

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-257007

Q15797

Q8N4C8

0

phosphorylation

down-regulates activity

0.2

Msn kinases directly phosphorylate α-helix 1 of Smad. we have identified Misshapen (Msn) and the mammalian orthologs TNIK, MINK1, and MAP4K4 as the kinases responsible for α-helix 1 phosphorylation.

SIGNOR-276336

P23443

P06493

0

phosphorylation

up-regulates

0.384

Interestingly, phosphorylation at several ser/thr residues within the c-terminal autoinhibitory tail appears to either activate or inhibit s6k1, depending on the cell cycle phase. phosphorylation of those residues (featured by the thr-421/ser-424 site) during mitosis pursued by cdk1 inactivates s6k1 we then assessed the phosphorylation status of the mitosis-specific inhibitory residue of s6k1, thr-421/ser-424, which is targeted by mitotic cdk1.

SIGNOR-111507

Q9NXK8

Q14012

1

ubiquitination

down-regulates quantity

0.475

Here, we show that a ubiquitin E3 ligase component, F-box protein Fbxl12, mediates CaMKI degradation via a proteasome-directed pathway leading to disruption of cyclin D1/cdk4 complex. Endogenous Fbxl12 and CaMKI interacted as demonstrated after Fbxl12 immuno-precipitation followed by immunoblot analysis with CaMKI antibodies assembly and resultantG1 arrest in lung epithelia. Fbxl12 targets CaMKI for ubiquitination.

SIGNOR-261193

P19784

Q15022

1

phosphorylation

up-regulates activity

0.2

CK2 is the kinase for the phosphorylation of S583 of SUZ12.

SIGNOR-277797

O00444

Q15154

1

phosphorylation

up-regulates activity

0.573

Plk4‚Äêmediated phosphorylation of PCM1 at S372 is critical for the proper localisation of centriolar satellites, its dimer formation and interaction with other satellite components|Therefore, Plk4 is responsible for PCM1 phosphorylation at S372.

SIGNOR-279556

Q9UMX1

Q8TBB1

0

ubiquitination

down-regulates quantity

0.2

Indeed, they target different lysine residues in the SuFu protein, as LNX1 ubiquitinates SuFu at K59 and K470, and SCF Fbxl17 acts at K257, while Itch ubiquitinates at K321 and K457.|XREF_FIG, ectopic LNX1 expression reduced SuFu protein levels in HEK-293T cells, while shRNA mediated knockdown of LNX1 increased these levels.

SIGNOR-278626

O60260

Q00535

0

phosphorylation

down-regulates

0.2

Phosphorylation by cdk5 decreased the auto-ubiquitylation of parkin both in vitro and in vivo.

SIGNOR-153445

Q8IWR1

Q9BQ95

2

binding

down-regulates activity

0.518

In this study, we showed that one of the TRIM family ubiquitin ligases, TRIM59, interacts with ECSIT as an adaptor protein required for the TLR-mediated transduction pathway. The B-box and RING domains of TRIM59 are important for interaction with ECSIT.|ECSIT enhances IPS-1-mediated IFN-Beta promoter activation.|Luciferase reporter assays using reporter plasmids including NF-kappaB responsive element, interferon beta (IFN-beta) promoter and interferon-sensitive response element (ISRE) showed that overexpression of TRIM59 repressed their transcriptional activities, whereas knockdown of TRIM59 enhanced their transcriptional activities.

SIGNOR-260369

P51813

P25116

1

phosphorylation

down-regulates activity

0.2

As shown in xref \u2013 xref , BMX overexpression increased PAR1-WT phosphorylation but had no effect on PAR1 Y 381 FY 383 F mutant, indicating that BMX phosphorylated PAR1 at Y 381 and Y 383 .|Mechanically , BMX represses PAR1 signaling in ECs by promoting PAR1 phosphorylation and internalization .

SIGNOR-279593

P78352

P12931

0

phosphorylation

up-regulates

0.565

These results indicate that psd-95 phosphorylation by src facilitates the integration of pyk2 to psd-95 signal complex, the activation of pyk2/src, as well as the subsequent tyrosine phosphorylation of nr2a, which ultimately results in the upregulation of nmda receptor function and synaptic transmission.

SIGNOR-205120

O96013

2

phosphorylation

up-regulates

0.2

Intracellular localization;enzymatic activity, induced;cell growth, altered;

SIGNOR-168301

P62837

O95071

1

ubiquitination

up-regulates activity

0.508

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-272668

P01137

P02452

1

transcriptional regulation

up-regulates quantity by expression

0.485

COL1A1 expression is regulated by upstream genes and the binding of regulatory elements at multiple binding sites upstream of its promoter. During cancer progression, CAFs reorganize and cross-link COL1A1, which accumulates and stiffens in the tumor stroma [12], [18]. This process may involve fibrogenic factors, especially transforming growth factor-beta (TGF-β1). Indeed, a TGF-β1 response sequence was identified 174 nucleotides upstream of the COL1A1 transcription start site, and was shown to up-regulate COL1A1 promoter activity

SIGNOR-277678

Q15139

Q05655

0

phosphorylation

up-regulates

0.269

Here we show that activation of pkd in response to oxidative stress requires two sequential signaling events, i.e., phosphorylation of tyr463 by abl, which in turn promotes a second step, phosphorylation of the pkd activation loop (ser738/ser742). We show that this is mediated by pkcdelta (protein kinase cdelta)

SIGNOR-123453

Q05655

P05107

1

phosphorylation

up-regulates

0.329

In this study, we present evidence that pkc isoforms are the major protein kinases that phosphorylate the c terminus of the integrin cd18 chain in leukocytes. Ser-745 is identified as a novel phosphorylation site in the integrin cytoplasmic domain. Additionally, we show that a thr-758-phosphorylated integrin peptide can interact with 14-3-3 proteins in leukocyte lysates

SIGNOR-178897

P25098

Q13304

1

phosphorylation

down-regulates activity

0.2

As depicted in Fig. 8 A and B, GRK2 silencing resulted in up-regulation of GPR17 and down-regulation of the mature markers CNPase and MBP, indicating a shift of cells toward a less differentiated stage.Having established that, in primary cultured OPCs, LTD 4 mediated desensitization of GPR17 through the primary recruitment of GRK2, we then asked whether GRK2 pharmacological inhibition had any effects on cysLT promoted cell maturation.|These data demonstrate that LTD 4 -induced GPR17 phosphorylation is preferentially mediated by GRK2 and only partially by GRK5, whereas UDP-glucose-mediated receptor phosphorylation exclusively requires the GRK5 isoform.We examined the involvement of GRK2 and GRK5 in agonist induced desensitization of GPR17.

SIGNOR-279999

Q8NEZ5

P04637

1

ubiquitination

down-regulates quantity by destabilization

0.338

We demonstrate here that SCFFbxo22-KDM4A is a senescence-associated E3 ligase targeting methylated p53 for degradation. We find that Fbxo22 is highly expressed in senescent cells in a p53-dependent manner, and that SCFFbxo22 ubiquitylated p53 and formed a complex with a lysine demethylase, KDM4A. |SCFFbxo22 forms a ternary complex with p53 and KDM4A that targets methylated p53 for degradation.

SIGNOR-273448

O43353

Q9Y4K3

2

binding

up-regulates activity

0.685

Binding of bacterial MDP or viral RNA to NOD2 results in the association of RIPK2 with TRAF6 and subsequent activation of TRAF6.

SIGNOR-280456

Q8TEW0

Q05513

0

phosphorylation

up-regulates

0.711

These results imply that serine 827 in the apkc binding site of par-3 is a target of apkc and that the regulated interaction between a protein kinase, apkc, and its substrate, par-3, plays an essential role in the establishment of cell polarity

SIGNOR-94523

O43791

P10070

1

ubiquitination

down-regulates quantity

0.71

RNAi knockdown of Spop (a substrate-binding adaptor for the cullin3-based ubiquitin E3 ligase) in Sufu mutant mouse embryonic fibroblasts (MEFs) can restore the levels of Gli2 and Gli3 full-length proteins

SIGNOR-268860

Q9NRM7

P17612

0

phosphorylation

up-regulates

0.2

Here, we show that cyclic amp (camp)-dependent protein kinase (pka) phosphorylates lats and thereby enhances its activity sufficiently to phosphorylate yap on ser381.

SIGNOR-236994

P62714

O14757

1

dephosphorylation

down-regulates activity

0.266

Phosphorylation of Chk1 by ATR is antagonized by a Chk1-regulated protein phosphatase 2A circuit|In response to genotoxic stress, Chk1 is phosphorylated on serines 317 (S317) and 345 (S345) by the ataxia-telangiectasia-related (ATR) protein kinase. Phosphorylation of Chk1 on these C-terminal serine residues is used as an indicator of Chk1 activation in vivo.

SIGNOR-248578

Q07666

P06213

0

phosphorylation

up-regulates activity

0.363

Thus, Tyr phosphorylation of Sam68 by IR could modulate its association with the splicing machinery in a similar way to that described for p59 fyn, and this way, it could influence splice site selection.

SIGNOR-278946

P41743

P61019

2

binding

down-regulates activity

0.456

Rab2 Binds to the PKCι/λ Regulatory Domain and Inhibits PKCι/λ-dependent GAPDH Phosphorylation

SIGNOR-261301

P16949

Q8NG68

2

binding

down-regulates

0.389

Stathmin depresses ttl tubulin tyrosination activityin vitro.

SIGNOR-193465

Q9UBE8

P46531

1

phosphorylation

down-regulates

0.382

Nlk-phosphorylated notch1icd is impaired in its ability to form a transcriptionally_ active_ ternary_ complex.

SIGNOR-163697

Q8IUR6

Q15011

1

transcriptional regulation

up-regulates quantity by expression

0.2

Luman/CREB3 induces transcription of the endoplasmic reticulum (ER) stress response protein Herp through an ER stress response element.

SIGNOR-261575

O76050

O76083

1

polyubiquitination

down-regulates quantity by destabilization

0.2

Neuralized family member NEURL1 is a ubiquitin ligase for the cGMP-specific phosphodiesterase 9A. We also demonstrate that NEURL1 can promote polyubiquitination of PDE9A that leads to its proteasome-mediated degradation mainly via lysine residue K27 of ubiquitin.

SIGNOR-272305

Q13569

Q9NZJ0

2

binding

down-regulates quantity by destabilization

0.358

TDG Is Polyubiquitinated by CRL4Cdt2 E3 Ubiquitin Ligase in a PIP Degron-dependent Manner

SIGNOR-272847

P54727

P23025

2

binding

up-regulates activity

0.769

GG-NER is initiated by the GG-NER specific factor XPC-RAD23B, in some cases with the help of UV-DDB (UV-damaged DNA-binding protein). TC-NER is initiated by RNA polymerase stalled at a lesion with the help of TC-NER specific factors CSA, CSB, and XAB2. Both pathways require the core NER factors to complete the excision process|The core NER dual incision reaction has been reconstituted in vitro with purified factors using XPC-RAD23B, TFIIH, XPA, RPA, XPG, and ERCC1-XPF (Aboussekhra et al. 1995; Mu et al. 1995; Araujo et al. 2000).|The core NER dual incision reaction has been reconstituted in vitro with purified factors using XPC-RAD23B, TFIIH, XPA, RPA, XPG, and ERCC1-XPF (Aboussekhra et al. 1995; Mu et al. 1995; Araujo et al. 2000). Functional studies revealed that XPC-RAD23B is the initial damage recognition factor in this system, as the presence of XPC-RAD23B is required for assembly of the other core NER factors and progression through the NER pathway both in vitro and in vivo

SIGNOR-275697

O60216

P23769

1

relocalization

down-regulates activity

0.325

Large-scale AML genome re-sequencing efforts have identified novel recurrently mutated genes, including the members of the cohesin complex (RAD21, SMC3, SMC1A, and STAG2), implicated in the pathogenesis of this disease.Using ATAC-seq, we determined that mutant cohesin lead to a state of elevated chromatin accessibility and higher predicted binding at transcription factor binding sites for ERG, GATA2, and RUNX1. Moreover, using ChIP-Seq, we formally demonstrated increased binding of GATA2 and RUNX1 to these sites. Finally, we demonstrated that knockdown of these three TFs in human HSPC can revert the differentiation block induced by mutant cohesin. These results support a model in which mutant cohesin impairs hematopoietic differentiation and enforces stem cell programs through the modulation of ERG, GATA2, and RUNX1 chromatin accessibility, expression, and activity.

SIGNOR-261513

P27694

Q9UMS4

0

polyubiquitination

up-regulates activity

0.509

PRP19 is a ubiquitin ligase involved in pre-mRNA splicing and the DNA damage response (DDR). PRP19 ubiquitylates RPA and promotes ATRIP recruitment.

SIGNOR-272076

Q92783

O60674

0

phosphorylation

up-regulates

0.617

Stam is associated with jak3 and jak2 tyrosine kinases via its itam region and phosphorylated by jak3 and jak2 upon stimulation with il-2.

SIGNOR-47834

P19086

P48039

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-257101

Q14247

Q8WZ74

2

binding

up-regulates activity

0.511

Fluorescence recovery after photobleaching further suggested that CTTNBP2 modulates the mobility of cortactin in neurons. CTTNBP2 may thus help to immobilize cortactin in dendritic spines and control the density of dendritic spines.

SIGNOR-269703

Q969T4

P25963

1

sumoylation

up-regulates quantity by stabilization

0.346

In the presence of an E1 SUMO-1-activating enzyme, Ubch9 conjugated SUMO-1 to IkappaBalpha primarily on K21, which is also utilized for ubiquitin modification. Thus, SUMO-1-modified IkappaBalpha cannot be ubiquitinated and is resistant to proteasome-mediated degradation.

SIGNOR-270545

O43561

P45983

0

phosphorylation

down-regulates

0.308

Lat, an adapter protein essential for t-cell signaling, is phosphorylated at its thr 155 by erk in response to t-cell receptor stimulation. Thr 155 phosphorylation reduces the ability of lat to recruit plcgamma1 and slp76, leading to attenuation of subsequent downstream events such as [ca2+]i mobilization and activation of the erk pathway.Mutational analysis revealed that t155 but not t94 or t140 is the site of jnk-mediated phosphorylation (figure 2b). Erk also phosphorylated lat at t155 (figure 2c), whereas p38, which was able to phosphorylate atf2, failed to induce threonine phosphorylation of lat (figure 2d). These results indicate that lat is directly phosphorylated by erk and jnk at the same site, t155.

SIGNOR-125774

Q5JVS0

P05771

0

phosphorylation

down-regulates activity

0.29

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

SIGNOR-249247

P21399

P17252

0

phosphorylation

down-regulates

0.2

Irp1 ser-711 is a phosphorylation site, critical for regulation of rna-binding and aconitase activities.

SIGNOR-133188

P05112

P31785

2

binding

up-regulates

0.858

The common gamma-chain (gamma(c)) is an indispensable subunit of the functional receptor complexes for il-4, il-7, il-9, and il-15 as well as il-2. Here we show that the gamma(c) is also shared with the il-21r complex

SIGNOR-108861

P23771

P17676

2

binding

down-regulates

0.352

In the present study, we demonstrate that both gata-2 and gata-3 form protein complexes with ccaat/enhancer binding protein alpha (c/ebpalpha) and c/ebpbeta, members of a family of transcription factors that are integral to adipogenesis. []the interaction between gata and c/ebp factors is critical for the ability of gata to suppress adipocyte differentiation.

SIGNOR-132952

Q53EL6

Q9Y297

0

ubiquitination

down-regulates

0.425

Both akt and p70(s6k) phosphorylate pdcd4, allowing for binding of the e3-ubiquitin ligase beta-trcp and consequently ubiquitylation.

SIGNOR-160985

Q9UHD2

O00571

1

phosphorylation

up-regulates activity

0.721

Coexpression of TBK1 strongly increased the activity of DDX3X.|This suggests that DDX3X is rather specifically phosphorylated by TBK1 and IKK-i.

SIGNOR-278997

P10415

Q86UR1

0

null

down-regulates activity

0.2

BH3-only proteins containing only a single BH domain and including Puma, Noxa, Bid and Bad as well as other factors are particularly important for such neutralisation, binding and regulating the anti-apoptotic Bcl-2 proteins to promote apoptosis

SIGNOR-209684

Q9Y613

Q13976

0

phosphorylation

up-regulates

0.354

Pkgi also directly phosphorylates fhod1, and studies with wild-type and mutant fhod1-derived peptides identify ser-1131 in the fhod1 c terminus as the unique pkgi phosphorylation site in fhod1. phosphorylation of three conserved residues within the dad domain activates fhod1 while binding to rac regulates fhod1 subcellular localization

SIGNOR-123646

Q13618

Q8N653

2

binding

up-regulates activity

0.273

Leucine zipper-like transcriptional regulator 1 (LZTR1) encodes a member of the BTB-Kelch superfamily, which interacts with the Cullin3 (CUL3)-based E3 ubiquitin ligase complex.

SIGNOR-269070

Q96EB6

P98177

1

deacetylation

up-regulates

0.744

Deacetylation of foxos involves binding of the nad-dependent deacetylase hsir2(sirt1). Accordingly, hsir2(sirt1)-mediated deacetylation precludes foxo inhibition through acetylation and thereby prolongs foxo-dependent transcription of stress-regulating genes.

SIGNOR-124714

P24928

Q9NP77

0

dephosphorylation

up-regulates activity

0.855

Phosphorylation of serine-2 (S2) and serine-5 (S5) of the C-terminal domain (CTD) of RNA polymerase II (RNAP II) is a dynamic process that regulates the transcription cycle and coordinates recruitment of RNA processing factors. The Fcp1 CTD phosphatase catalyzes dephosphorylation of S2-P.| Depletion of Ssu72 impairs transcription in vitro

SIGNOR-248815

Q02750

P28482

2

phosphorylation

up-regulates activity

0.75

Mapk1 is phosphorylated by map2k1/mek1 and map2k2/mek2 on thr-185 and tyr-187 in response to external stimuli like insulin or ngf. Both phosphorylations are required for activity.

SIGNOR-236447

P17676

Q8N695

1

transcriptional regulation

up-regulates quantity by expression

0.2

Luciferase reporter assays of deletion mutants of SLC5A8 promoter demonstrated that a 295-bp region is essential for the basal promoter activity of the SLC5A8 gene. Further analysis indicated that the CCAAT boxes and GC boxes were involved in positive regulation of SLC5A8 promoter. Overexpression of two transcription factors, CCAAT/enhancer binding protein beta (C/EBPbeta) and specific transcription factor 1 (Sp1), upregulated the activities of the human SLC5A8 promoter and protein expression, suggesting that both C/EBPbeta and Sp1 transcription factors might have functions in SLC5A8 transcription.

SIGNOR-254054

Q99677

P63092

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 ‚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-256785

P47900

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-256943

P06241

Q16539

1

phosphorylation

up-regulates

0.489

T cell src family kinases and zap70 activate p38 by phosphorylating tyr323.

SIGNOR-134293

P30989

P34947

0

phosphorylation

up-regulates activity

0.594

Here we report the unique phosphorylation\nof NTSR1 by GRK2 and GRK5, which belong to the GRK2 and GRK4 subfamilies,\nrespectively.

SIGNOR-278234

P19838

P04150

0

transcriptional regulation

down-regulates quantity by repression

0.6

We have described how the receptor uses several means to achieve repression of the genes regulated by AP-1 and NF-KB proteins

SIGNOR-251680

P00519

P29350

1

phosphorylation

up-regulates activity

0.414

The results demonstrate that the SH3 domain of ABL1 interacts with a WPDHGVPSEP motif (residues 417-426) in the catalytic domain of SHPTP1 and that ABL1 phosphorylates C terminal Y536 and Y564 sites.

SIGNOR-260820

P67775

P35222

1

dephosphorylation

up-regulates

0.462

In the absence of the wt apc protein, phosphorylated beta-catenin is rapidly dephosphorylated by serine/threonine protein phosphatase 2a (pp2a). phosphorylated beta-catenin associated with the wild-type apc protein is recruited to the scf(beta-trcp) complex, ubiquitin conjugated, and degraded.

SIGNOR-182637

P55036

Q05086

0

polyubiquitination

down-regulates quantity by destabilization

0.463

S5a/Rpn10 is a ubiquitin (Ub)-binding protein that is a subunit of the 26S proteasome but also exists free in the cytosol. It binds poly-Ub chains through its two Ub-interacting motifs (UIMs). We discovered that, unlike typical substrates of Ub ligases (E3s), S5a can be ubiquitinated by all E3s tested including multimeric and monomeric Ring finger E3s (MuRF1, Siah2, Parkin, APC, and SCF(betaTRCP1)), the U-box E3, CHIP, and HECT domain E3s (E6AP and Nedd4) when assayed with UbcH5 or related Ub-conjugating enzymes.The short half-life of S5a presumably is because of the presence of the UIM domain and reflects the ubiquitination of free S5a by many E3s. Surprisingly, the same four Lys residues on S5a, Lys-74, Lys-122, Lys-262, and Lys-365 were ubiquitinated by MuRF1 and E6AP (Fig. 10). Two additional Lys residues (Lys-126 and -135) were ubiquitinated by E6AP.

SIGNOR-272746

O14640

O75084

2

binding

up-regulates

0.661

In non-canonical Wnt signalling, Wnt proteins bind Fzd and glypican-4, to activate Dsh at the cell membrane, leading to activation of Rho and JNK

SIGNOR-255893

O43251

O14920

0

phosphorylation

up-regulates activity

0.2

Phosphorylation of RTA by IKKbeta increases RTA transcriptional activity and consequently viral mRNA production.

SIGNOR-279336

Q15121

P31749

0

phosphorylation

up-regulates activity

0.517

Protein kinase b/akt binds and phosphorylates ped/pea-15, stabilizing its antiapoptotic action.

SIGNOR-102092

Q13651

P22301

2

binding

up-regulates

0.914

Functionally active il-10 receptors are composed of two distinct subunits. The il-10 receptor ? Chain is a 110-kda polypeptide that plays the dominant role in mediating high affinity ligand binding and signal transduction. The il-10 receptor ? Subunit (also known as crf2_4) is predicted to be a 40-kda polypeptide that is largely required only for signaling

SIGNOR-67964

P08754

P35346

2

binding

up-regulates activity

0.45

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-256833

P06744

Q9UKV5

2

binding

up-regulates

0.53

Pgi is a housekeeping gene encoding phosphoglucose isomerase (pgi) a glycolytic enzyme that also functions as a cytokine (autocrine motility factor (amf)/neuroleukin/maturation factor) upon secretion from the cell and binding to its 78 kda seven-transmembrane domain receptor (gp78/amf-r)

SIGNOR-97270

Q00535

Q05397

1

phosphorylation

up-regulates

0.305

Here, we show that fak phosphorylation by cdk5 at s732 is important for microtubule organization, nuclear movement, and neuronal migration. In cultured neurons, s732-phosphorylated fak is enriched along a centrosome-associated microtubule fork that abuts the nucleus. Overexpression of the nonphosphorylatable mutant fak s732a results in disorganization of the microtubule fork and impairment of nuclear movement in vitro, and neuronal positioning defects in vivo.

SIGNOR-86223

P49757

Q00987

2

binding

down-regulates

0.444

Numb interacts with mdm2, and inhibits its ubiquitin-ligase function on tp53 (which in itself is inhibitory for tp53), thus numb activates (b) tp53

SIGNOR-168454

P20807

P49840

1

cleavage

up-regulates activity

0.2

Thus, it has been shown that calpain cleaves the inhibitory domain of GSK3 generating two fragments of 40 and 30 kDa. This cleavage enhanced activity of the kinase

SIGNOR-251606

P30411

P25098

0

phosphorylation

down-regulates activity

0.2

Ligand-induced phosphorylation is found at Ser339 and Ser346/Ser348 that could be executed by several G protein-coupled receptor kinases. 32P labeling of peptide 3 containing pS346/pS348 was enhanced 1.5–3-fold as compared with mock-transfected cells in the order GRK6 < GRK5 < GRK2 < GRK4α < GRK3. several endogenous GRKs may phosphorylate the B2R and that the various GRKs, even without apparent effect on total GPCR phosphorylation levels, may induce distinct phosphorylation patterns with possible functional consequences for receptor desensitization and sequestration.

SIGNOR-251445

P36894

P12643

2

binding

up-regulates

0.929

BMP interacts with specific receptors on the cell surface, BMP receptor types 1 and 2 (BMPr1 and BMPr2).

SIGNOR-253547

P21127

Q07955

1

phosphorylation

up-regulates activity

0.283

In comparison, CLK1 expression leads to speckle dissolution and diffuse GFP-SRSF1 localization in the nucleus.|We showed that CLK1 phosphorylates SRSF1 at approximately 18 sites inducing a gel shift from 35 to about 38 kDa on SDS-PAGE (XREF_FIG, upper panel).

SIGNOR-279499

Q13535

Q8N163

1

phosphorylation

up-regulates activity

0.438

Here, we report that, in human cell lines, DNA damage triggered the phosphorylation of DBC1 on Thr454 by ATM (ataxia telangiectasia-mutated) and ATR (ataxia telangiectasia and Rad3-related) kinases. Phosphorylated DBC1 bound to and inhibited SIRT1, resulting in the dissociation of the SIRT1-p53 complex and stimulating p53 acetylation and p53-dependent cell death.

SIGNOR-267662

O00141

P28482

1

phosphorylation

up-regulates activity

0.309

SGK1 was found to physically interact with ERK1/2 as well as MEK1/2. Furthermore, SGK1 mediated the phosphorylation of ERK2 on Ser(29) in a serum-dependent manner. Replacement of Ser(29) to aspartic acid, which mimics the phosphorylation of Ser(29), enhanced the ERK2 activity as well as the MEK/ERK complexes formation.

SIGNOR-276223

P19174

P35968

2

binding

up-regulates

0.675

(vegfr) phosphorylated y1175 creates a binding site for phospholipase cgamma1 (plc-gamma1)

SIGNOR-147870

Q08828

P63092

2

binding

up-regulates activity

0.627

Because adenylyl cyclases are directly activated by G(s)alpha and the carboxyl termini of the various Galpha proteins determine their receptor coupling specificity, we proposed a set of chimeric G(s)alpha where the COOH-terminal five amino acids are replaced by those of other Galpha proteins and used these to dissect the potential Galpha linked to a given GPCR

SIGNOR-156958

Q13627

P13807

1

phosphorylation

down-regulates activity

0.267

DYRK Family Protein Kinases Phosphorylate and Inactivate Glycogen Synthase. both protein kinases phosphorylate site 3a but no other sites that affect glycogen synthase activity.

SIGNOR-260632

P38936

O43293

0

phosphorylation

up-regulates quantity by stabilization

0.316

ZIP kinase phosphorylates p21(WAF1) at Thr145 and alanine-substituted mutations in the p21(WAF1) phosphorylation site alter its ability to be phosphorylated by ZIP kinase. | Transfected ZIPK can promote the phosphorylation of p21(WAF1) at Thr145 in vivo and can increase the half-life of p21(WAF1)

SIGNOR-251085

P05112

O95644

0

transcriptional regulation

up-regulates quantity by expression

0.549

Recombinant NFAT1 can mediate transcription of the interleukin-2, interleukin-4, tumor necrosis factor alpha, and granulocyte-macrophage colony-stimulating factor promoters in T cells, suggesting that NFAT1 contributes to the CsA-sensitive transcription of these genes during the immune response.

SIGNOR-254498

P06239

P07766

1

phosphorylation

up-regulates activity

0.692

Tyrosine Phosphorylation of CD8- Chimeras by Lck and ZAP-70 in COS Cells. both Y170F and Y181F chimeric proteins could be efficiently phosphorylated by Lck in vivo. phosphorylation of Y170 and Y181 within CD3- –ITAM provides to CD3- the potential to interact with multiple downstream effectors and signaling pathways.

SIGNOR-251369

Q92949

P48380

2

binding

up-regulates activity

0.548

RFX3 acts as a transcriptional co-activator to FOXJ1 that enhances the expression of cilia-associated genes. FOXJ1 is an important regulator of cilia gene expression during ciliated cell differentiation, with RFX3 as a transcriptional co-activator to FOXJ1, helping to induce the expression of cilia genes in the process of ciliated cell differentiation of basal/progenitor cells.

SIGNOR-266929

Q8WU20

P04629

2

binding

up-regulates

0.779

The signaling adapter frs-2 competes with shc for binding to the nerve growth factor receptor trka:a model for discriminating proliferation and differentiation

SIGNOR-65955

Q13153

P16333

2

binding

up-regulates activity

0.709

Both nck and grb4 proteins could associate with receptor tyrosine kinases and the sh3-binding proteins pak, sos1, and prk2, and they synergized with v-abl and sos to induce gene expression via the transcription factor elk-1. Association of nck with pak1 may serve to link this important regulatory kinase to cell activation by growth factor receptors.

SIGNOR-236512

Q5TZA2

Q96CN5

2

binding

up-regulates activity

0.44

Here, we show that LRRC45 is a centrosome linker that localizes at the proximal ends of the centrioles and forms fiber-like structures between them. Depletion of LRRC45 results in centrosome splitting during interphase. LRRC45 interacts with C-Nap1 and rootletin

SIGNOR-273704

O43318

Q12933

0

ubiquitination

up-regulates activity

0.597

Tumor necrosis factor receptor-associated factors 2 and 6 (traf2 and -6) act as the ubiquitin e3 ligases to mediate lys63-linked tak1 polyubiquitination at the lys158 residue in vivo and in vitro. Lys(63)-linked TAK1 polyubiquitination at the Lys(158) residue is required for TAK1-mediated IKK complex recruitment.

SIGNOR-162638

Q96GX5

2

phosphorylation

up-regulates activity

0.2

After this priming step, Gwl can intramolecularly phosphorylate its C-terminal tail at pS883; this site probably plays a role similar to that of the tail/Z motif of other AGC kinases.

SIGNOR-243409

O43683

Q8NG31

2

binding

up-regulates

0.2

Association of the amino and middle domain of blinkin with the tpr domains in the amino termini of bubr1 and bub1 is essential for bubr1 and bub1 to execute their distinct mitotic functions

SIGNOR-158378

Q9UGL1

O94992

0

relocalization

up-regulates activity

0.2

We previously reported that the tumor suppressor HEXIM1 is a mediator of KDM5B recruitment to its target genes, and HEXIM1 is required for the inhibition of nuclear hormone receptor activity by KDM5B.

SIGNOR-273439

P31749

P23769

1

phosphorylation

down-regulates

0.524

We show that insulin induces gata2 phosphorylation on serine 401 in a pi-3k/akt-dependent manner. Insulin-dependent phosphorylation of serine 401 impairs gata2 translocation to the nucleus and its dna binding activity

SIGNOR-135614

P45985

P45984

1

phosphorylation

up-regulates

0.729

Mkk4, which activates p38gamma, p38delta, and jnk2 to phosphorylate p53 on ser-33 and cause a transient g(1) arrest. A map kinase kinase kinase (mapkkk), termed ask1, was identified that activated two different subs of map kinase kinases (mapkk), sek1 (or mkk4) and mkk3/mapkk6 (or mkk6), which in turn activated stress-activated protein kinase (sapk, also known as jnk;c-jun amino-terminal kinase) here we report that mkk4 shows a striking preference for the tyrosine residue (tyr-185), and mkk7 a striking preference for the threonine residue (thr-183) in three sapk1/jnk1 isoforms tested (jnk1 alpha 1, jnk2 alpha 2 and jnk3 alpha 1)

SIGNOR-197998

P11309

P42229

0

transcriptional regulation

up-regulates quantity by expression

0.375

The results of 2 microarray experiments demonstrated that the aberrant activation of STAT proteins by Flt3-ITDs resulted in the up-regulation of several STAT5-responsive genes, such as Pim-1, Pim-2, and members of the SOCS (suppressor of cytokine signaling) protein family. These results are particularly interesting because recent data point to an important role of Pim kinases in the antiapoptosis of hematopoietic cells.

SIGNOR-249621

Q8TEK3

P01106

2

binding

up-regulates activity

0.334

Our data suggest that the c-Myc-dependent transcriptional switch is modulated by DOT1L, as in the presence of DOT1L c-Myc preferentially forms an active complex with p300 rather than a repressive complex containing HDAC1 and DNMT1

SIGNOR-239362

P55347

P14653

2

binding

up-regulates activity

0.613

we observe the formation of a ternary Prep1-Pbx1-HOXB1 complex on a HOXB1-responsive target in vitro. Interaction with Prep1 enhances the ability of the HOXB1-Pbx1 complex to activate transcription in a cooperative fashion from the same target.

SIGNOR-241215