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
Q9Y259	P17612	0	phosphorylation	up-regulates activity	0.253	Choline kinase beta (CKbeta) is one of the CK isozymes involved in the biosynthesis of phosphatidylcholine. \| This study provides evidence for CKβ phosphorylation by protein kinase A (PKA).\|Phosphorylation sites were located on CKβ residues serine-39 and serine-40 as determined by mass spectrometry and site-directed mutagenesis. Phosphorylation increased the catalytic efficiencies for the substrates choline and ATP about 2-fold, without affecting ethanolamine phosphorylation, and the S39D/S40D CKβ phosphorylation mimic behaved kinetically very similar.	SIGNOR-275629
P49815	P54646	0	phosphorylation	up-regulates	0.577	We have observed that ampk directly phosphorylates tsc2, and the ampk-dependent phosphorylation of tsc2 is critical for the coordination between cell growth and cellular energy levels.	SIGNOR-149388
P45984	O43521	1	phosphorylation	up-regulates activity	0.637	JNKs specifically phosphorylate BIMEL at Ser55, 65, and/or 73. several observations demonstrate that the phosphorylation of BIMEL is a physiologically important mechanism for enhancing its proapoptotic activity.	SIGNOR-250134
P10721	P21583	2	binding	up-regulates activity	0.934	The most relevant and still unique mast-cell growth factor is SCF, which is the ligand of KIT, a receptor with tyrosine-kinase activity that is expressed on the surface of all human and murine mast cells	SIGNOR-254946
P31749	P54198	1	phosphorylation	up-regulates activity	0.2	Consistently, HIRA phosphorylation was effectively decreased by Akt1 knockdown and was completely eliminated by the depletion of both Akt1 and Akt2, suggesting that HIRA is phosphorylated primarily by Akt1 and that Akt2 seemed to contribute to HIRA phosphorylation as a supplementary kinase in myoblasts (XREF_FIG).\|In this study, HIRA was more efficiently targeted by Akt1 in myoblasts.	SIGNOR-279584
Q9UKL3	Q14790	2	binding	up-regulates	0.448	The caspase-8-binding protein flice-associated huge protein (flash) would form a molecular complex with caspase-8, thereby presumably activating the mitochondrial apoptosis pathway by regulating caspase-8 activity.	SIGNOR-152473
P33981	P38646	1	phosphorylation	up-regulates	0.2	Mortalin binds to mps1, and is phosphorylated by mps1 on thr62 and ser65. The phosphorylated mortalin then super-activates mps1 in a feedback manner. Mps1-associated acceleration of centrosome duplication depends on the presence of mortalin and super-activation by the thr62/ser65 phosphorylated mortalin	SIGNOR-156185
P12931	P45984	0	phosphorylation	up-regulates activity	0.355	Activation of c-Src by JNK2 was accompanied by the phosphorylation of c-Src on threonine residue (s).\|JNK2 directly phosphorylates c-Src and activates its auto phosphorylation.	SIGNOR-279221
O14920	P08151	1	phosphorylation	up-regulates activity	0.356	Active IKKbeta promotes the stability of GLI1 oncogene in diffuse large B-cell lymphoma.\|Herein, we demonstrate that IKKbeta phosphorylates GLI1 in DLBCL.	SIGNOR-279194
Q9UPQ7	O15146	1	ubiquitination	down-regulates quantity	0.543	We have identified a PDZ domain containing RING finger 3 (PDZRN3) as a synapse-associated E3 ubiquitin ligase and have demonstrated that it regulates the surface expression of muscle-specific receptor tyrosine kinase (MuSK), the key organizer of postsynaptic development at the mammalian neuromuscular junction. PDZRN3 binds to MuSK and promotes its ubiquitination. Together, these data demonstrate that PDZRN3 is a catalytically active RING-type E3 ubiquitin ligase	SIGNOR-271664
Q9HCE7-2	Q9H469	2	binding	down-regulates quantity by destabilization	0.56	Here, we report that F-box and LRR domain-containing protein 15 (FBXL15), an F-box protein of the FBXL family, forms an Skp1-Cullin1-F-box protein-Roc1 (SCF)(FBXL15) ubiquitin ligase complex and targets Smurf1 for ubiquitination and proteasomal degradation. FBXL15, through its leucine-rich repeat domain, specifically recognizes the large subdomain within the N-lobe of the Smurf1 HECT domain and promotes the ubiquitination of Smurf1 on K355 and K357 within the WW-HECT linker region. In this way, FBXL15 positively regulates BMP signalling in mammalian cells.	SIGNOR-271909
P17612	P32245	1	phosphorylation	down-regulates activity	0.308	Activation of MC4R by agonist is associated with protein kinase A (PKA) and GRK phosphorylation of serine/threonine residues in the C-terminal tail of MC4R, followed by -arrestin and dynamin-dependent internalization of the receptor. Thr312 and Ser329/330 in the C-terminal tail of MC4R are potential sites for PKA	SIGNOR-250016
P18887	O96017	0	phosphorylation	up-regulates	0.515	Chk2 formed a complex with xrcc1, the ber scaffold protein, and phosphorylated xrcc1 in vivo and in vitro at thr(284). our results are consistent with the phosphorylation of xrcc1 by atm-chk2 facilitating recruitment of downstream ber proteins to the initial damage recognition/excision step to promote ber.	SIGNOR-181816
Q99623	P15172	2	binding	down-regulates	0.365	Phb2 interacts with both myod and mef2, and represses both myod- and mef2-dependent gene transcription. Furthermore, binding of phb2 to both myod and mef2 significantly decreases upon myogenic differentiation.	SIGNOR-235843
Q15465	Q5VTY9	0	palmitoylation	up-regulates	0.683	Our molecular analysis of knockout mice deficient in skn, the murine homolog of the drosophila ski gene, which catalyzes hh palmitoylation, and gene-targeted mice producting a non palmitoylated form of shh indicates that hh palmitoylation is essential for its activity as well as the generation of a protein gradient in the developing embryos	SIGNOR-124118
O15550	P11308	1	transcriptional regulation	down-regulates quantity by repression	0.2	Our findings reveal a dual role for UTX in suppressing acute myeloid leukaemia via repression of oncogenic ETS and upregulation of tumor suppressive GATA programs. several ETS transcription factors, including Elf4, Etv6, Erg, Fli1, Ets2, Spi1 and Elk3 were upregulated immediately after Utx loss in the preleukaemic phase	SIGNOR-260033
Q14493	Q8IUE6	1	translation regulation	up-regulates quantity by expression	0.2	Synthesis of mature histone mRNA requires only a single processing reaction: an endonucleolytic cleavage between a conserved stem-loop and a purine-rich downstream element to form the 3' end. The stem-loop binding protein (SLBP) is required for processing, and following processing, histone mRNA is transported to the cytoplasm, where SLBP participates in translation of the histone mRNA\|We used radiolabeled probes generated by PCR targeting the open reading frame (ORF) to detect histones H2A, H2B, H3, H4, and H1 and used 7SK snRNA as a loading control (Fig. 2A). The abundance of histone H2A, H2B, H3, and H4 mRNAs is reduced to 37% to 70% of control levels in the SLBP knockdown cells when compared to the C2 control.	SIGNOR-265406
O15392	P04637	2	binding	down-regulates	0.562	This study identifies the anti-apoptotic survivin gene as a p53-repressed gene;notably, survivin repression by p53 is shown to be distinct from p53-dependent growth arrest.	SIGNOR-111971
Q86YC2	Q13535	0	phosphorylation	up-regulates activity	0.307	ATR promotes PALB2 accumulation at DNA damage sites.\|In the context of PALB2 regulation, the phosphorylation of PALB2 by ATR plays a positive role in PALB2 recruitment.	SIGNOR-279588
Q06587	Q13642	2	binding	up-regulates	0.357	The polycombprotein ring1 interacts with the lim domains of kyot2 in yeast and mammalian cells. The interaction between kyot2 and ring1 was detected both in vitro and in vivo	SIGNOR-123150
P04083	P05771	0	phosphorylation	up-regulates	0.2	The authors identified several phosphorylated residues by a combination of peptide mapping and sequence analysis and showed that recombinant pp60c-src phosphorylates annexin a1 near its amino terminus, at tyrosine 21 (tyr21). Also polyoma virus middle t/pp60c-src complex, recombinant pp50v-abl, and the egf receptor/kinase phosphorylated the same tyrosine residue. It was also shown that serine 27 residue of anxa1 is the primary site phosphorylated by protein kinase c (pkc). In the same study, the threonine 41 residue has been identified as a pkc substrate as well. The adenosine cyclic 3_,5_-phosphate dependent protein kinase a (pka) phosphorylates anxa1 in its carboxyl-terminal core at the threonine 216 residue (thr216) [2].The phosphorylation of serine 27 is essential for annexin a1 membrane localization.	SIGNOR-202784
P46937	Q9Y297	0	ubiquitination	down-regulates	0.544	This cascade of phosphorylation allows the binding of scfbetatrcp that promotes the ubiquitination and degradation of yap.	SIGNOR-201138
P28482	P20749	1	phosphorylation	up-regulates activity	0.474	Here we show that Akt, Erk2, and IKK1/2 phosphorylate Bcl3. Phosphorylation of Ser33 by Akt induces switching of K48 ubiquitination to K63 ubiquitination and thus promotes nuclear localization and stabilization of Bcl3. Phosphorylation by Erk2 and IKK1/2 of Ser114 and Ser446 converts Bcl3 into a transcriptional coregulator by facilitating its recruitment to DNA.	SIGNOR-277361
Q14653	Q9BYM8	0	polyubiquitination	down-regulates quantity by destabilization	0.325	Here we show that the E3 ubiquitin ligase RBCC protein interacting with PKC1 (RBCK1) catalyzes the ubiquitination and degradation of IRF3. We transfected 293 cells with expression plasmids for Flag-IRF3, HA-ubiquitin, and HA-RBCK1. Coimmunoprecipitation and western blot analysis indicated that RBCK1 significantly polyubiquitinated IRF3 (Figure 4D).	SIGNOR-271737
Q00987	Q92993	1	polyubiquitination	down-regulates quantity by destabilization	0.654	Furthermore, we provide evidence that Mdm2, the ubiquitin ligase of the p53 tumour suppressor, interacts physically with Tip60 and induces its ubiquitylation and proteasome-dependent degradation.	SIGNOR-272613
P60953	Q96N96	0	guanine nucleotide exchange factor	up-regulates activity	0.718	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-260576
Q8NFZ3	Q9HDB5	2	binding	up-regulates activity	0.2	Pre- and postsynaptic plasma membranes are always precisely aligned, and are separated by a synaptic cleft of ~20 nm. The cleft contains an undefined proteinaceous material in the middle, and is presumably bridged by synaptic cell-adhesion molecules such as Nrxns and Nlgns that align the pre- and postsynaptic elements and mediate trans-synaptic signaling.\|Nlgns bind to both alpha- and beta-Nrxns with nanomolar affinities; binding involves the sixth LNS-domain of alpha-Nrxns which corresponds to the only LNS-domain of beta-Nrxns52. The binding affinities differ characteristically between various pairs of Nlgns and Nrxns, and are controlled by alternative splicing of both Nrxns and Nlgns (Figure 1c)	SIGNOR-264168
Q9UQB3	Q00535	0	phosphorylation	up-regulates activity	0.327	Cdk5 mediated delta-catenin phosphorylation regulates delta-catenin subcellular localization into two distinct pools : a cytoplasmic or intraneurite state as well as a pool that is localized to the membrane.\|Cdk5 phosphorylates delta-catenin on serines 300 and 357.	SIGNOR-279323
Q13263	O96017	0	phosphorylation	down-regulates activity	0.411	In particular, Chk2 phosphorylates KAP1 on Ser473 decreasing the interaction between KAP1 and HP1 proteins: this post translational modification promotes HP1\u03b2 mobilization and the reorganization of chromatin structure favoring the repair of DNA breaks inside heterochromatin [ , ].\|Of note, phosphorylation of S473 by Chk2 decreases the interaction between KAP1 and HP1 proteins and is necessary for HP1\u03b2 mobilization, a key event for DNA repair in the heterochromatin [ - ].	SIGNOR-279730
P51681	P35626	0	phosphorylation	down-regulates activity	0.2	Serine residues at positions 336, 337, 342, and 349 represent GRK phosphorylation sites on CCR5. CCR5 phosphorylation and desensitization through a GRK-mediated mechanism	SIGNOR-251463
P41221	Q9Y625	2	binding	down-regulates activity	0.374	GPC6 binds to Wnt5a and inhibits its release from producing cells. Based on theseresults, and in our finding that GPC6 inhibits non-canonical Wnt signaling in the developing intestine,we tested the hypothesis that GPC6 binds to Wnt5aat the surface of the Wnt5a-producing mesenchymalcells and restrains its release from them.	SIGNOR-264030
P78536	Q16539	0	phosphorylation	up-regulates activity	0.405	We show that p38 MAP kinase, which is activated in response to inflammatory or stress signals, directly activates TACE, a membrane-associated metalloprotease that is also known as ADAM17 and effects shedding in response to growth factors and Erk MAP kinase activation. p38alpha MAP kinase interacts with the cytoplasmic domain of TACE and phosphorylates it on Thr(735), which is required for TACE-mediated ectodomain shedding	SIGNOR-163970
O60674	P46527	1	phosphorylation	down-regulates activity	0.696	JAK2 phosphorylates tyrosine residue 88 (Y88) of p27(Kip1).	SIGNOR-278260
P42224	P23470	0	dephosphorylation	up-regulates activity	0.2	PTPRG activation by the P1-WD peptide affected the tyrosine phosphorylation of several signaling molecules. Data analysis identified 31 molecules whose phosphorylation was modified in a statistically significant manner (Table I). inhibition of ABL1, BMX, BTK, DAB1, ITGB1, JAK2, KDR, KIT, LIMK1, MET, PDGFRB, SHC1, and VCL correlates with tyrosine dephosphorylation. In contrast, SRC inhibition correlates with hyperphosphorylation of the inhibitory Tyr530 residue and with dephosphorylation of the activatory Tyr419. Moreover, CDK2 and CTTN inhibition correlates with a hyperphosphorylation of the inhibitory Tyr15 and Tyr470, respectively. In contrast, a subgroup of 13 proteins, including BLNK, DOK2, ERBB2, GRIN2B, INSR, PDGFRA, PRKCD, PXN, STAT1, STAT2, STAT3, STAT5A, and ZAP70, appears to be activated by PTPRG activity.	SIGNOR-254727
P40763	Q14526	2	binding	down-regulates quantity by repression	0.367	HIC1 interacts with the DNA binding domain of STAT3 and suppresses the binding of STAT3 to its target gene promoters. HIC1 C-terminal domain binds to STAT3. HIC1 mutant defective in STAT3 interaction reduced its repressive effect on STAT3 DNA binding activity, the reporter activity and gene expression of the VEGF and c-Myc genes, and cell growth in MDA-MB 231 cells.	SIGNOR-254246
Q9UBS0	Q15633	1	phosphorylation	up-regulates activity	0.333	We demonstrate that S6 kinases can phosphorylate the extended C-terminal domain of TRBP and interact with TRBP in situ in primary cells. TRBP serines 283/286 are essential for S6K-mediated TRBP phosphorylation, optimal expression of TRBP, and the S6K-TRBP interaction in human primary cells.	SIGNOR-274066
Q13315	P38398	1	phosphorylation	up-regulates	0.819	Results from this study indicate that the checkpoint protein kinase atm (mutated in ataxia telangiectasia) was required for phosphorylation of brca1 in response to ionizing radiation. Brca1 is phosphorylated at tyrosine residues in an atm-dependent, radiation-dependent manner.	SIGNOR-72075
Q6IMN6	O75581	2	binding	up-regulates	0.358	A cytoplasmic protein in vertebrates, referred to as caprin-2, binds to lrp6 and facilitates lrp6 phosphorylation by gsk3	SIGNOR-187177
P35790	Q14693	1	phosphorylation	down-regulates activity	0.273	Because CKI is a constitutively active kinase and ubiquitously distributed in many cell types, high mTORC1 activity depending on nutritional status may be a physiological cue for Lipin1 degradation mediated by CKI and beta-TRCP.\|Thus, we propose that mTORC1 may function as a priming kinase for CKI to promote the phosphorylation of the degron motif in Lipin1.	SIGNOR-280228
P68400	Q15019	1	phosphorylation	down-regulates	0.2	Here we show that human septin 2 is phosphorylated in vivo at ser218 by casein kinase ii. Septin 2 binds and hydrolyses gtp. The purified protein has the capacity to polymerize into long filaments when loaded with gtp or gdp. Moreover, we show that the endogenous protein in hela cells, like that produced in insect cells, is phosphorylated by casein kinase ii and that this phosphorylation alters nucleotide binding.	SIGNOR-148010
P51955	P04637	1	phosphorylation	down-regulates	0.318	NEK2 Phosphorylates p53 at Ser315 and Reduces Its Stability.\|These results are consistent with NEK2 inhibiting p53 transcriptional activation functions.	SIGNOR-278488
P41240	P17612	0	phosphorylation	up-regulates activity	0.338	Activation of the cooh-terminal src kinase (csk) by camp-dependent protein kinase inhibits signaling through the t cell receptor.Pka phosphorylates csk at s364 in vitro and in vivo leading to a two- to fourfold increase in csk activity that is necessary for camp-mediated inhibition of tcr-induced interleukin 2 secretion.	SIGNOR-105229
P06239	Q9NP31	1	phosphorylation	up-regulates activity	0.578	Here we mapped Lck phosphorylation and interaction sites on TSAd and evaluated their functional importance. The three C-terminal TSAd tyrosines Tyr(280), Tyr(290), and Tyr(305) were phosphorylated by Lck and functioned as docking sites for the Lck Src homology 2 (SH2) domain. Lck binds to TSAd prolines and phosphorylates and interacts with the three C-terminal TSAd tyrosines. We propose that through multivalent interactions with Lck, TSAd diverts Lck from phosphorylating other substrates, thus modulating its functional activity through substrate competition.	SIGNOR-262888
Q9NRY4	P61586	1	gtpase-activating protein	down-regulates activity	0.893	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-260492
P49023	Q05397	2	binding	up-regulates activity	0.914	Focal adhesion kinase (FAK) is activated by growth factors and integrins during migration, and functions as a receptor-proximal regulator of cell motility. At contacts between cells and the extracellular matrix, FAK functions as an adaptor protein to recruit other focal contact proteins or their regulators, which affects the assembly or disassembly of focal contacts. Whereas it was first hypothesized that FAK might bind directly to the cytoplasmic tails of integrins, accumulated evidence supports an indirect association of FAK with integrins through binding to integrin-associated proteins such as paxillin and talin.	SIGNOR-257732
O14672	P26378	0	post transcriptional regulation	up-regulates quantity	0.2	Neuronal ELAV (nELAV) proteins are RNA-binding proteins which play a physiological role in controlling gene expression in memory formation, and their alteration may contribute to cognitive impairment associated with neurodegenerative pathologies such as Alzheimer's disease (AD). The experiments show for the first time that ADAM10mRNA represents a nELAV target and that these RNA-binding proteins can play a role in the post-transcriptional regulation of ADAM10 expression. nELAV proteins specifically bind the ADAM10 mRNA and this binding is disrupted following Aβ exposure	SIGNOR-266865
P29350	P43405	1	dephosphorylation	down-regulates	0.737	We propose that shp1 can dephosphorylate sites in zap-70 and syk that are involved in coupling these kinases to downstream signaling cascades, including erk2 and elements of the il-2 gene.	SIGNOR-70234
Q92565	P01116	1	guanine nucleotide exchange factor	up-regulates	0.436	Gefs catalyse the transition from gdp-bound, inactive ras to gtp-bound, active ras.	SIGNOR-183735
O43521	P45984	0	phosphorylation	up-regulates activity	0.637	JNKs specifically phosphorylate BIMEL at Ser55, 65, and/or 73. several observations demonstrate that the phosphorylation of BIMEL is a physiologically important mechanism for enhancing its proapoptotic activity.	SIGNOR-250134
Q15256	P49023	1	dephosphorylation	down-regulates activity	0.2	Here, we show that paxillin is a direct substrate of PTPRT and that PTPRT specifically regulates paxillin phosphorylation at tyrosine residue 88 (Y88) in colorectal cancer (CRC) cells. We engineered CRC cells homozygous for a paxillin Y88F knock-in mutant and found that these cells exhibit significantly reduced cell migration and impaired anchorage-independent growth,	SIGNOR-248720
P49840	O15084	1	phosphorylation	down-regulates activity	0.2	We provide evidence for a dual kinase-mediated regulation of the PITK holoenzyme whereby PITK phosphorylation at S1017 is catalyzed by calcium/calmodulin-dependent kinase II-delta (CaMKIIdelta), promoting the subsequent phosphorylation of S1013 by glycogen synthase kinase-3 (GSK3) in vitro.\|the phosphorylation of PITK at these specific residues altered PP1 binding and subsequent PITK-directed dephosphorylation of hnRNP K	SIGNOR-264792
Q92643	Q96S52	2	binding	up-regulates activity	0.943	To determine roles for PIG-S and PIG-T, we disrupted these genes in mouse F9 cells by homologous recombination. PIG-S and PIG-T knockout cells were defective in transfer of GPI to proteins, particularly in formation of the carbonyl intermediates. We also demonstrate that PIG-S and PIG-T form a protein complex with GAA1 and GPI8, and that PIG-T maintains the complex by stabilizing the expression of GAA1 and GPI8.	SIGNOR-261362
O96013	Q15139	0	phosphorylation	up-regulates activity	0.252	When PKD3 was knocked-down using isoform-specific shRNA (PKD3-shRNA), PAK4 activity (judged by its phosphorylation status at the activation loop using the pS474-PAK4 antibody) was decreased	SIGNOR-275930
P60953	P12931	0	phosphorylation	up-regulates	0.695	Epidermal growth factor-dependent regulation of cdc42 is mediated by the src tyrosine kinaseegf signaling through src appears to have dual regulatory effects on cdc42: 1). it leads to the activation of cdc42 as mediated by the vav2 guanine nucleotide exchange factor, and 2). it results in the phosphorylation of cdc42, which stimulates the binding of rhogdi, perhaps to direct the movement of cdc42 to a specific cellular site to trigger a signaling response, because cdc42-rhogdi interactions are essential for cdc42-induced cellular transformation.	SIGNOR-118206
Q14289	Q05397	1	phosphorylation	up-regulates	0.524	Activated rock phosphorylates fak on ser732, which is essential for phosphorylation of tyr407 and for cell migration. We further show that pyk2 is activated by vegf-induced clustering of integrin v 3 and is responsible for the phosphorylation of tyr407.	SIGNOR-147070
P55211	P98170	2	binding	down-regulates quantity by destabilization	0.922	A conserved XIAP-interaction motif in caspase-9 and Smac/DIABLO regulates caspase activity and apoptosis	SIGNOR-105702
P42336	P63215	2	binding	up-regulates	0.385	Gbetagamma subunits released from gi can activate pi3k (phosphoinositide 3-kinase), and can be therefore implicated in smo-dependent activation of akt	SIGNOR-145125
P43686	Q92630	0	phosphorylation	down-regulates quantity by destabilization	0.284	Through a kinome-wide screen, we have identified dual-specificity tyrosine-regulated kinase 2 (DYRK2) as the primary kinase that phosphorylates Rpt3-Thr25, leading to enhanced substrate translocation and degradation.	SIGNOR-275845
Q16539	Q15717	1	phosphorylation	up-regulates	0.523	P38 mapk phosphorylates the mrna binding protein hur on thr118, which results in cytoplasmic accumulation of hur and its enhanced binding to the p21cip1 mrna.	SIGNOR-186135
Q4VCS5	Q9H0M0	0	ubiquitination	up-regulates quantity by stabilization	0.275	Here low serum and high LATS1 activity are found to enhance the levels of the 130-kDa isoform of angiomotin (Amot130) through phosphorylation by LATS1/2 at serine 175, which then forms a binding site for 14-3-3. Such phosphorylation, in turn, enables the ubiquitin ligase atrophin-1 interacting protein (AIP)4 to bind, ubiquitinate, and stabilize Amot130	SIGNOR-275847
Q8IZL8	Q9NU22	2	binding	up-regulates quantity by stabilization	0.377	MDN1 Is Physically and Functionally Associated with the Mammalian PELP1 Complex. To more specifically determine a function of mammalian MDN1 in the subnuclear distribution of PELP1-containing pre-60S-particles, we examined PELP1 localization in control cells or cells depleted from MDN1. Importantly, in the absence of MDN1, PELP1 became sequestered in enlarged nucleoli, indicating that MDN1 is involved in the nucleolar release of PELP1-containing pre-60S ribosomes	SIGNOR-261357
P29350	P23458	1	dephosphorylation	down-regulates	0.646	We find, for the first time, that shp-1 down-regulates the level of tyk2 kinase in h9 cells and of jak1 kinase in htb26 cells, by accelerating their degradation.	SIGNOR-119197
P49841	P56693	1	phosphorylation	down-regulates quantity	0.406	Besides, GSK3\u03b2 phosphorylates SOX10 at CPD domain and facilitates Fbxw7\u03b1-mediated SOX10 degradation.\|Besides, GSK3beta phosphorylates SOX10 at CPD domain and facilitates Fbxw7alpha mediated SOX10 degradation.	SIGNOR-279617
Q9UM73	Q9UM73	2	phosphorylation	up-regulates activity	0.2	ALK SelectiVely Phosphorylates the First Tyrosine in Its A-Loop Peptide.	SIGNOR-250575
O95837	P28222	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-257207
P37840	P48729	0	phosphorylation	up-regulates	0.371	In vitro experiments and two-dimensional phosphopeptide mapping provided further evidence that serine 129 was phosphorylated by ck-1 and ck-2. Moreover, phosphorylation of serine 129 was reduced in vivo upon inhibition of ck-1 or ck-2. These data demonstrate that alpha-synuclein is constitutively phosphorylated within its c terminus and may indicate that the function of alpha-synuclein is regulated by phosphorylation/dephosphorylation.From these data we conclude that _-synuclein is predominantly phosphorylated at serine residue 129. However, a second serine at position 87 is also used for phosphorylation to some extent. together, these data may indicate that ck-1 and ck-2 are involved in the regulation of neuronal function and one may speculate that phosphorylation of _-synuclein could affect its binding to membranes.	SIGNOR-73799
Q96G91	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-256931
Q15303	P35070	2	binding	up-regulates	0.723	For example, betacellulin binds to and activates both erbb1 and erbb4, whereas epiregulin binds to erbb1, erbb3 and erbb4	SIGNOR-195347
Q9Y297	O15534	1	ubiquitination	down-regulates	0.57	We have found that per1 interacts with both _-trcp1 and _-trcp2 in a manner that depends on casein kinase 1 activity, and depletion of both _-trcp1 and _-trcp2 by rnai leads to dramatic stabilization of per1	SIGNOR-137755
P08575	P06241	1	dephosphorylation	up-regulates activity	0.73	On the membrane SKAP55, via its phosphorylated Tyr-271, further binds the SH2 domain of Fyn to replace the low-affinity bound inhibitory site of the kinase. Consequently, CD45 may have transiently disassociated with the Tyr-232 residue of SKAP55 through dephosphorylation and simultaneously interacted with the released the phosphorylated inhibitory tyrosine residue of Fyn for dephosphorylation, resulting in activation of the Src family kinase Fyn and initiation of TCR-engaged signal transduction.	SIGNOR-248352
P35222	Q9ULB5	2	binding	up-regulates activity	0.568	At its C-terminus, cadherin interacts with Î²-catenin, which dynamically associates with Î±-catenin, a direct binding partner of filamentous actin	SIGNOR-265869
P30550	P38405	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-256917
P00533	P28482	0	phosphorylation	down-regulates activity	0.639	A growth factor-stimulated protein kinase activity that phosphorylates the epidermal growth factor (EGF) receptor at Thr669 has been described Anion-exchange chromatography demonstrated that this protein kinase activity was accounted for by two enzymes. The first peak of activity eluted from the column corresponded to the microtubule-associated protein 2 (MAP2) kinase	SIGNOR-20545
Q03113	Q9HC97	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-257204
P13288	Q14653	1	phosphorylation	down-regulates activity	0.2	BGLF4 kinase interacts physically with and phosphorylates IRF3, which is the initial activator of transcription in the innate immune response. BGLF4 suppresses IRF3-dependent transcriptional activation. Data here suggest that Ser123, Ser173, and Thr180 contribute additively to the BGLF4-mediated repression of the IRF3 transactivation activity.	SIGNOR-266647
Q6PGQ7	P49841	0	phosphorylation	up-regulates	0.258	It suggests that gsk3_ activity is required for hbora-mediated mitotic entry through ser274 and ser278 phosphorylation	SIGNOR-201519
P41221	Q01974	2	binding	up-regulates	0.775	Wnt5a induces ROR1/ROR2 heterooligomerization to enhance leukemia chemotaxis and proliferation\|Evolutionarily conserved receptor tyrosine kinase–like orphan receptor-1 and -2 (ROR1/2) are considered distinct receptors for Wnt5a and are implicated in noncanonical Wnt signaling in organogenesis and cancer metastasis.	SIGNOR-199647
Q9BYT3	Q5JQC9	1	phosphorylation	up-regulates quantity by stabilization	0.2	Differential phosphoproteomic analysis and in vitro kinase assay identified novel phosphorylation substrates of STK33, fibrous sheath components AKAP3 and AKAP4, whose expression levels decreased in testis after deletion of Stk33.	SIGNOR-272956
P63092	Q03431	2	binding	up-regulates activity	0.506	This calciotropic hormone exerts its actions via binding to the PTH/PTH-related peptide receptor (PTH1R), which couples to multiple heterotrimeric G proteins, including Gs and Gq/11.	SIGNOR-270551
P49761	Q07955	1	phosphorylation	up-regulates activity	0.531	In vitro, Clk/Sty efficiently phosphorylated the SR family member ASF/SF2 on serine residues located within its serine/arginine-rich region (the RS domain). Overexpression of the active Clk/Sty kinase caused a redistribution of SR proteins within the nucleus. These results suggest that Clk/Sty kinase directly regulates the activity and compartmentalization of SR splicing factors.	SIGNOR-273859
Q15172	Q01484	0	relocalization	up-regulates quantity	0.282	Ankyrin-B is targeted to the M-line via its interaction with the C-terminal domain of the large sarcomeric protein obscurin. Obscurin is targeted to the M-line via its N-terminal interactions with myomesin and titin. This population of ankyrin-B recruits B56α, a regulatory subunit of protein phosphatase 2A, to the M-line where the phosphatase may regulate the phosphorylation status of contractile and signalling proteins.	SIGNOR-266729
Q13207	P23760	0	transcriptional regulation	up-regulates quantity by expression	0.346	We have recently found that a T-box gene family member, TBX2, is highly overexpressed in both ERMS and ARMS cells (Zhu et al, 2014). The regulation of TBX2 is uncharacterised in RMS cells, but is likely to link TBX2 expression to the known deregulation of signalling pathways in RMS. In melanoma cells, TBX2 is regulated by PAX3	SIGNOR-249596
Q92830	P68431	1	acetylation	down-regulates activity	0.2	The HAT module within the SAGA and ADA complexes acetylates histone H3, mainly on residues K9 and K14.	SIGNOR-269602
P62136	P42575	1	dephosphorylation	up-regulates activity	0.2	nutrient-replete oocytes inhibit C2 via S135 phosphorylation catalyzed by calcium/calmodulin-dependent protein kinase II. We now show that C2 phosphorylated at S135 binds 14-3-3zeta, thus preventing C2 dephosphorylation. Moreover, we determined that S135 dephosphorylation is catalyzed by protein phosphatase-1 (PP1), which directly binds C2.	SIGNOR-248564
P17861-2	Q96EB6	0	deacetylation	down-regulates activity	0.379	P300 increases the acetylation and protein stability of XBP1s, and enhances its transcriptional activity, whereas SIRT1 deacetylates XBP1s and inhibits its transcriptional activity.. The mRNA encoding the active spliced form of XBP1 (XBP1s) is generated from the unspliced form by IRE1 (inositol-requiring enzyme 1) during the UPR.	SIGNOR-260430
Q12864	P35222	2	binding	up-regulates activity	0.705	At its C-terminus, cadherin interacts with Î²-catenin, which dynamically associates with Î±-catenin, a direct binding partner of filamentous actin	SIGNOR-265856
Q03135	P06241	0	phosphorylation	down-regulates activity	0.721	Caveolin-1 is phosphorylated on tyr(14) in response to both oxidative and hyperosmotic stress. In the present paper, we show that this phosphorylation requires activation of the src family kinase fyn.Therefore,	SIGNOR-118003
Q08378	Q16584	0	phosphorylation	up-regulates activity	0.361	In vitro kinase assays demonstrated that MLK3 directly phosphorylates golgin-160 in the N-terminal head region between residues 96 and 259.	SIGNOR-279065
P51451	P12318	1	phosphorylation	up-regulates activity	0.436	To identify the FcgammaRII-phosphorylating protein tyrosine kinase (PTK), we used the combination of an in vitro and an in vivo approach. In an in vitro assay using recombinant cytoplasmic tails of the different FcgammaRII isoforms as well as tyrosine exchange mutants, we show that each of the BCR-associated PTKs (Lyn, Blk, Fyn, and Syk) shows different phosphorylation patterns with regard to the different FcgammaR isoforms and point\|Fyn and Blk definitely phosphorylate Y-282 in the ITAM of Fc_RIIa/c, whereas the non-ITAM tyrosine residue (Y-275) becomes phosphorylated by Syk, as the phosphorylation of double point mutants shows. In addi-tion to these tyrosine residues, Fyn, Blk, and Syk might phosphorylate the most C-terminal tyrosine residue (Y-298) because altering this tyrosine residue together with one of the tyrosine residues clearly shown to be phosphorylated by the respective PTK results in the abrogation of phosphorylation.	SIGNOR-249312
Q9NQS7	Q96GD4	2	binding	up-regulates	0.974	Using recombinant proteins, we found that aurora b kinase activity was stimulated by incenp and that the c-terminal region of incenp was sufficient for activation.	SIGNOR-86218
P52945	O43791	0	ubiquitination	down-regulates quantity	0.326	Pdx1 C terminus-interacting factor-1 (Pcif1, also known as SPOP) is a nuclear protein that inhibits Pdx1 transactivation. Here, we show that Pcif1 targets Pdx1 for ubiquitination and proteasomal degradation.	SIGNOR-268859
P23771	Q99835	0	null	up-regulates activity	0.2	That GATA is a downstream effector of the hedgehog pathway.	SIGNOR-253527
Q9H4X1	P06493	2	binding	up-regulates activity	0.53	RGC-32 was physically associated with cyclin-dependent kinase p34CDC2 and increased the kinase activity in vivo and in vitro. In addition, RGC-32 was phosphorylated by p34CDC2-cyclin B1 in vitro. Mutation of RGC-32 protein at Thr-91 prevented the p34CDC2-mediated phosphorylation and resulted in loss of p34CDC2 kinase enhancing activity.	SIGNOR-262726
P68400	P20042	1	phosphorylation	up-regulates	0.35	The n-terminal domain of the human eif2beta subunit and the ck2 phosphorylation sites are required for its function. These results suggest that ser2 and ser67 contribute to the important role of the n-terminal region of eif2beta for its function in mammals.	SIGNOR-140994
Q05682	Q00535	0	phosphorylation	down-regulates quantity by destabilization	0.341	Together, these data demonstrate that phosphorylation of caldesmon on Ser527 by Cdk5 serves to down regulate its stability.	SIGNOR-280215
Q96BR9	Q8TBB1	0	polyubiquitination	down-regulates quantity by destabilization	0.2	LNX (ligand of Numb protein-X) is a RING finger and four PDZ domain-containing E3 ubiquitin ligase. Lnx-l induced K48-linked polyubiquitylation of Boz, leading to its proteasomal degradation in human 293T cells and in zebrafish embryos.	SIGNOR-272777
P52757	P06239	0	phosphorylation	down-regulates activity	0.2	We now demonstrate Lck-dependent phosphorylation of beta2-chimaerin in response to TCR triggering. We identify Tyr-153 as the Lck-dependent phosphorylation residue and show that its phosphorylation negatively regulates membrane stabilization of beta2-chimaerin, decreasing its GAP activity to Rac.	SIGNOR-276240
Q12798	O43303	2	binding	up-regulates activity	0.483	We report that CP110 interacts with two different Ca2+-binding proteins, calmodulin (CaM) and centrin, in vivo. our data demonstrate a functional role for CaM binding to CP110 and suggest that CP110 cooperates with CaM and centrin to regulate progression through cytokinesis.	SIGNOR-265966
P04792	Q05655	0	phosphorylation	down-regulates activity	0.515	Radioactive kinase assays confirmed that PKC\u03b4 phosphorylated Hsp27 at Ser78 and Ser82 ( Fig. 3 B).	SIGNOR-278425
O94901	Q3KP22	2	binding	up-regulates activity	0.2	In this study, we found that SUN1 not only interacted with TERB1 but also interacted with MAJIN, and the interaction of SUN1 with MAJIN is stronger than TERB1. We also found that SUN1 interacted with SPDYA, an activator of CDK2. \| It will be of great interest to test this hypothesis to fully understand the mechanisms of stable telomere–NE connection and telomere movement along the NE driven by the LINC complex.	SIGNOR-263300

Q9Y259

P17612

0

phosphorylation

up-regulates activity

0.253

Choline kinase beta (CKbeta) is one of the CK isozymes involved in the biosynthesis of phosphatidylcholine. | This study provides evidence for CKβ phosphorylation by protein kinase A (PKA).|Phosphorylation sites were located on CKβ residues serine-39 and serine-40 as determined by mass spectrometry and site-directed mutagenesis. Phosphorylation increased the catalytic efficiencies for the substrates choline and ATP about 2-fold, without affecting ethanolamine phosphorylation, and the S39D/S40D CKβ phosphorylation mimic behaved kinetically very similar.

SIGNOR-275629

P49815

P54646

0

phosphorylation

up-regulates

0.577

We have observed that ampk directly phosphorylates tsc2, and the ampk-dependent phosphorylation of tsc2 is critical for the coordination between cell growth and cellular energy levels.

SIGNOR-149388

P45984

O43521

1

phosphorylation

up-regulates activity

0.637

JNKs specifically phosphorylate BIMEL at Ser55, 65, and/or 73. several observations demonstrate that the phosphorylation of BIMEL is a physiologically important mechanism for enhancing its proapoptotic activity.

SIGNOR-250134

P10721

P21583

2

binding

up-regulates activity

0.934

The most relevant and still unique mast-cell growth factor is SCF, which is the ligand of KIT, a receptor with tyrosine-kinase activity that is expressed on the surface of all human and murine mast cells

SIGNOR-254946

P31749

P54198

1

phosphorylation

up-regulates activity

0.2

Consistently, HIRA phosphorylation was effectively decreased by Akt1 knockdown and was completely eliminated by the depletion of both Akt1 and Akt2, suggesting that HIRA is phosphorylated primarily by Akt1 and that Akt2 seemed to contribute to HIRA phosphorylation as a supplementary kinase in myoblasts (XREF_FIG).|In this study, HIRA was more efficiently targeted by Akt1 in myoblasts.

SIGNOR-279584

Q9UKL3

Q14790

2

binding

up-regulates

0.448

The caspase-8-binding protein flice-associated huge protein (flash) would form a molecular complex with caspase-8, thereby presumably activating the mitochondrial apoptosis pathway by regulating caspase-8 activity.

SIGNOR-152473

P33981

P38646

1

phosphorylation

up-regulates

0.2

Mortalin binds to mps1, and is phosphorylated by mps1 on thr62 and ser65. The phosphorylated mortalin then super-activates mps1 in a feedback manner. Mps1-associated acceleration of centrosome duplication depends on the presence of mortalin and super-activation by the thr62/ser65 phosphorylated mortalin

SIGNOR-156185

P12931

P45984

0

phosphorylation

up-regulates activity

0.355

Activation of c-Src by JNK2 was accompanied by the phosphorylation of c-Src on threonine residue (s).|JNK2 directly phosphorylates c-Src and activates its auto phosphorylation.

SIGNOR-279221

O14920

P08151

1

phosphorylation

up-regulates activity

0.356

Active IKKbeta promotes the stability of GLI1 oncogene in diffuse large B-cell lymphoma.|Herein, we demonstrate that IKKbeta phosphorylates GLI1 in DLBCL.

SIGNOR-279194

Q9UPQ7

O15146

1

ubiquitination

down-regulates quantity

0.543

We have identified a PDZ domain containing RING finger 3 (PDZRN3) as a synapse-associated E3 ubiquitin ligase and have demonstrated that it regulates the surface expression of muscle-specific receptor tyrosine kinase (MuSK), the key organizer of postsynaptic development at the mammalian neuromuscular junction. PDZRN3 binds to MuSK and promotes its ubiquitination. Together, these data demonstrate that PDZRN3 is a catalytically active RING-type E3 ubiquitin ligase

SIGNOR-271664

Q9HCE7-2

Q9H469

2

binding

down-regulates quantity by destabilization

0.56

Here, we report that F-box and LRR domain-containing protein 15 (FBXL15), an F-box protein of the FBXL family, forms an Skp1-Cullin1-F-box protein-Roc1 (SCF)(FBXL15) ubiquitin ligase complex and targets Smurf1 for ubiquitination and proteasomal degradation. FBXL15, through its leucine-rich repeat domain, specifically recognizes the large subdomain within the N-lobe of the Smurf1 HECT domain and promotes the ubiquitination of Smurf1 on K355 and K357 within the WW-HECT linker region. In this way, FBXL15 positively regulates BMP signalling in mammalian cells.

SIGNOR-271909

P17612

P32245

1

phosphorylation

down-regulates activity

0.308

Activation of MC4R by agonist is associated with protein kinase A (PKA) and GRK phosphorylation of serine/threonine residues in the C-terminal tail of MC4R, followed by -arrestin and dynamin-dependent internalization of the receptor. Thr312 and Ser329/330 in the C-terminal tail of MC4R are potential sites for PKA

SIGNOR-250016

P18887

O96017

0

phosphorylation

up-regulates

0.515

Chk2 formed a complex with xrcc1, the ber scaffold protein, and phosphorylated xrcc1 in vivo and in vitro at thr(284). our results are consistent with the phosphorylation of xrcc1 by atm-chk2 facilitating recruitment of downstream ber proteins to the initial damage recognition/excision step to promote ber.

SIGNOR-181816

Q99623

P15172

2

binding

down-regulates

0.365

Phb2 interacts with both myod and mef2, and represses both myod- and mef2-dependent gene transcription. Furthermore, binding of phb2 to both myod and mef2 significantly decreases upon myogenic differentiation.

SIGNOR-235843

Q15465

Q5VTY9

0

palmitoylation

up-regulates

0.683

Our molecular analysis of knockout mice deficient in skn, the murine homolog of the drosophila ski gene, which catalyzes hh palmitoylation, and gene-targeted mice producting a non palmitoylated form of shh indicates that hh palmitoylation is essential for its activity as well as the generation of a protein gradient in the developing embryos

SIGNOR-124118

O15550

P11308

1

transcriptional regulation

down-regulates quantity by repression

0.2

Our findings reveal a dual role for UTX in suppressing acute myeloid leukaemia via repression of oncogenic ETS and upregulation of tumor suppressive GATA programs. several ETS transcription factors, including Elf4, Etv6, Erg, Fli1, Ets2, Spi1 and Elk3 were upregulated immediately after Utx loss in the preleukaemic phase

SIGNOR-260033

Q14493

Q8IUE6

1

translation regulation

up-regulates quantity by expression

0.2

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

SIGNOR-265406

O15392

P04637

2

binding

down-regulates

0.562

This study identifies the anti-apoptotic survivin gene as a p53-repressed gene;notably, survivin repression by p53 is shown to be distinct from p53-dependent growth arrest.

SIGNOR-111971

Q86YC2

Q13535

0

phosphorylation

up-regulates activity

0.307

ATR promotes PALB2 accumulation at DNA damage sites.|In the context of PALB2 regulation, the phosphorylation of PALB2 by ATR plays a positive role in PALB2 recruitment.

SIGNOR-279588

Q06587

Q13642

2

binding

up-regulates

0.357

The polycombprotein ring1 interacts with the lim domains of kyot2 in yeast and mammalian cells. The interaction between kyot2 and ring1 was detected both in vitro and in vivo

SIGNOR-123150

P04083

P05771

0

phosphorylation

up-regulates

0.2

The authors identified several phosphorylated residues by a combination of peptide mapping and sequence analysis and showed that recombinant pp60c-src phosphorylates annexin a1 near its amino terminus, at tyrosine 21 (tyr21). Also polyoma virus middle t/pp60c-src complex, recombinant pp50v-abl, and the egf receptor/kinase phosphorylated the same tyrosine residue. It was also shown that serine 27 residue of anxa1 is the primary site phosphorylated by protein kinase c (pkc). In the same study, the threonine 41 residue has been identified as a pkc substrate as well. The adenosine cyclic 3_,5_-phosphate dependent protein kinase a (pka) phosphorylates anxa1 in its carboxyl-terminal core at the threonine 216 residue (thr216) [2].The phosphorylation of serine 27 is essential for annexin a1 membrane localization.

SIGNOR-202784

P46937

Q9Y297

0

ubiquitination

down-regulates

0.544

This cascade of phosphorylation allows the binding of scfbetatrcp that promotes the ubiquitination and degradation of yap.

SIGNOR-201138

P28482

P20749

1

phosphorylation

up-regulates activity

0.474

Here we show that Akt, Erk2, and IKK1/2 phosphorylate Bcl3. Phosphorylation of Ser33 by Akt induces switching of K48 ubiquitination to K63 ubiquitination and thus promotes nuclear localization and stabilization of Bcl3. Phosphorylation by Erk2 and IKK1/2 of Ser114 and Ser446 converts Bcl3 into a transcriptional coregulator by facilitating its recruitment to DNA.

SIGNOR-277361

Q14653

Q9BYM8

0

polyubiquitination

down-regulates quantity by destabilization

0.325

Here we show that the E3 ubiquitin ligase RBCC protein interacting with PKC1 (RBCK1) catalyzes the ubiquitination and degradation of IRF3. We transfected 293 cells with expression plasmids for Flag-IRF3, HA-ubiquitin, and HA-RBCK1. Coimmunoprecipitation and western blot analysis indicated that RBCK1 significantly polyubiquitinated IRF3 (Figure 4D).

SIGNOR-271737

Q00987

Q92993

1

polyubiquitination

down-regulates quantity by destabilization

0.654

Furthermore, we provide evidence that Mdm2, the ubiquitin ligase of the p53 tumour suppressor, interacts physically with Tip60 and induces its ubiquitylation and proteasome-dependent degradation.

SIGNOR-272613

P60953

Q96N96

0

guanine nucleotide exchange factor

up-regulates activity

0.718

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-260576

Q8NFZ3

Q9HDB5

2

binding

up-regulates activity

0.2

Pre- and postsynaptic plasma membranes are always precisely aligned, and are separated by a synaptic cleft of ~20 nm. The cleft contains an undefined proteinaceous material in the middle, and is presumably bridged by synaptic cell-adhesion molecules such as Nrxns and Nlgns that align the pre- and postsynaptic elements and mediate trans-synaptic signaling.|Nlgns bind to both alpha- and beta-Nrxns with nanomolar affinities; binding involves the sixth LNS-domain of alpha-Nrxns which corresponds to the only LNS-domain of beta-Nrxns52. The binding affinities differ characteristically between various pairs of Nlgns and Nrxns, and are controlled by alternative splicing of both Nrxns and Nlgns (Figure 1c)

SIGNOR-264168

Q9UQB3

Q00535

0

phosphorylation

up-regulates activity

0.327

Cdk5 mediated delta-catenin phosphorylation regulates delta-catenin subcellular localization into two distinct pools : a cytoplasmic or intraneurite state as well as a pool that is localized to the membrane.|Cdk5 phosphorylates delta-catenin on serines 300 and 357.

SIGNOR-279323

Q13263

O96017

0

phosphorylation

down-regulates activity

0.411

In particular, Chk2 phosphorylates KAP1 on Ser473 decreasing the interaction between KAP1 and HP1 proteins: this post translational modification promotes HP1\u03b2 mobilization and the reorganization of chromatin structure favoring the repair of DNA breaks inside heterochromatin [ , ].|Of note, phosphorylation of S473 by Chk2 decreases the interaction between KAP1 and HP1 proteins and is necessary for HP1\u03b2 mobilization, a key event for DNA repair in the heterochromatin [ - ].

SIGNOR-279730

P51681

P35626

0

phosphorylation

down-regulates activity

0.2

Serine residues at positions 336, 337, 342, and 349 represent GRK phosphorylation sites on CCR5. CCR5 phosphorylation and desensitization through a GRK-mediated mechanism

SIGNOR-251463

P41221

Q9Y625

2

binding

down-regulates activity

0.374

GPC6 binds to Wnt5a and inhibits its release from producing cells. Based on theseresults, and in our finding that GPC6 inhibits non-canonical Wnt signaling in the developing intestine,we tested the hypothesis that GPC6 binds to Wnt5aat the surface of the Wnt5a-producing mesenchymalcells and restrains its release from them.

SIGNOR-264030

P78536

Q16539

0

phosphorylation

up-regulates activity

0.405

We show that p38 MAP kinase, which is activated in response to inflammatory or stress signals, directly activates TACE, a membrane-associated metalloprotease that is also known as ADAM17 and effects shedding in response to growth factors and Erk MAP kinase activation. p38alpha MAP kinase interacts with the cytoplasmic domain of TACE and phosphorylates it on Thr(735), which is required for TACE-mediated ectodomain shedding

SIGNOR-163970

O60674

P46527

1

phosphorylation

down-regulates activity

0.696

JAK2 phosphorylates tyrosine residue 88 (Y88) of p27(Kip1).

SIGNOR-278260

P42224

P23470

0

dephosphorylation

up-regulates activity

0.2

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

SIGNOR-254727

P40763

Q14526

2

binding

down-regulates quantity by repression

0.367

HIC1 interacts with the DNA binding domain of STAT3 and suppresses the binding of STAT3 to its target gene promoters. HIC1 C-terminal domain binds to STAT3. HIC1 mutant defective in STAT3 interaction reduced its repressive effect on STAT3 DNA binding activity, the reporter activity and gene expression of the VEGF and c-Myc genes, and cell growth in MDA-MB 231 cells.

SIGNOR-254246

Q9UBS0

Q15633

1

phosphorylation

up-regulates activity

0.333

We demonstrate that S6 kinases can phosphorylate the extended C-terminal domain of TRBP and interact with TRBP in situ in primary cells. TRBP serines 283/286 are essential for S6K-mediated TRBP phosphorylation, optimal expression of TRBP, and the S6K-TRBP interaction in human primary cells.

SIGNOR-274066

Q13315

P38398

1

phosphorylation

up-regulates

0.819

Results from this study indicate that the checkpoint protein kinase atm (mutated in ataxia telangiectasia) was required for phosphorylation of brca1 in response to ionizing radiation. Brca1 is phosphorylated at tyrosine residues in an atm-dependent, radiation-dependent manner.

SIGNOR-72075

Q6IMN6

O75581

2

binding

up-regulates

0.358

A cytoplasmic protein in vertebrates, referred to as caprin-2, binds to lrp6 and facilitates lrp6 phosphorylation by gsk3

SIGNOR-187177

P35790

Q14693

1

phosphorylation

down-regulates activity

0.273

Because CKI is a constitutively active kinase and ubiquitously distributed in many cell types, high mTORC1 activity depending on nutritional status may be a physiological cue for Lipin1 degradation mediated by CKI and beta-TRCP.|Thus, we propose that mTORC1 may function as a priming kinase for CKI to promote the phosphorylation of the degron motif in Lipin1.

SIGNOR-280228

P68400

Q15019

1

phosphorylation

down-regulates

0.2

Here we show that human septin 2 is phosphorylated in vivo at ser218 by casein kinase ii. Septin 2 binds and hydrolyses gtp. The purified protein has the capacity to polymerize into long filaments when loaded with gtp or gdp. Moreover, we show that the endogenous protein in hela cells, like that produced in insect cells, is phosphorylated by casein kinase ii and that this phosphorylation alters nucleotide binding.

SIGNOR-148010

P51955

P04637

1

phosphorylation

down-regulates

0.318

NEK2 Phosphorylates p53 at Ser315 and Reduces Its Stability.|These results are consistent with NEK2 inhibiting p53 transcriptional activation functions.

SIGNOR-278488

P41240

P17612

0

phosphorylation

up-regulates activity

0.338

Activation of the cooh-terminal src kinase (csk) by camp-dependent protein kinase inhibits signaling through the t cell receptor.Pka phosphorylates csk at s364 in vitro and in vivo leading to a two- to fourfold increase in csk activity that is necessary for camp-mediated inhibition of tcr-induced interleukin 2 secretion.

SIGNOR-105229

P06239

Q9NP31

1

phosphorylation

up-regulates activity

0.578

Here we mapped Lck phosphorylation and interaction sites on TSAd and evaluated their functional importance. The three C-terminal TSAd tyrosines Tyr(280), Tyr(290), and Tyr(305) were phosphorylated by Lck and functioned as docking sites for the Lck Src homology 2 (SH2) domain. Lck binds to TSAd prolines and phosphorylates and interacts with the three C-terminal TSAd tyrosines. We propose that through multivalent interactions with Lck, TSAd diverts Lck from phosphorylating other substrates, thus modulating its functional activity through substrate competition.

SIGNOR-262888

Q9NRY4

P61586

1

gtpase-activating protein

down-regulates activity

0.893

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-260492

P49023

Q05397

2

binding

up-regulates activity

0.914

Focal adhesion kinase (FAK) is activated by growth factors and integrins during migration, and functions as a receptor-proximal regulator of cell motility. At contacts between cells and the extracellular matrix, FAK functions as an adaptor protein to recruit other focal contact proteins or their regulators, which affects the assembly or disassembly of focal contacts. Whereas it was first hypothesized that FAK might bind directly to the cytoplasmic tails of integrins, accumulated evidence supports an indirect association of FAK with integrins through binding to integrin-associated proteins such as paxillin and talin.

SIGNOR-257732

O14672

P26378

0

post transcriptional regulation

up-regulates quantity

0.2

Neuronal ELAV (nELAV) proteins are RNA-binding proteins which play a physiological role in controlling gene expression in memory formation, and their alteration may contribute to cognitive impairment associated with neurodegenerative pathologies such as Alzheimer's disease (AD). The experiments show for the first time that ADAM10mRNA represents a nELAV target and that these RNA-binding proteins can play a role in the post-transcriptional regulation of ADAM10 expression. nELAV proteins specifically bind the ADAM10 mRNA and this binding is disrupted following Aβ exposure

SIGNOR-266865

P29350

P43405

1

dephosphorylation

down-regulates

0.737

We propose that shp1 can dephosphorylate sites in zap-70 and syk that are involved in coupling these kinases to downstream signaling cascades, including erk2 and elements of the il-2 gene.

SIGNOR-70234

Q92565

P01116

1

guanine nucleotide exchange factor

up-regulates

0.436

Gefs catalyse the transition from gdp-bound, inactive ras to gtp-bound, active ras.

SIGNOR-183735

O43521

P45984

0

phosphorylation

up-regulates activity

0.637

JNKs specifically phosphorylate BIMEL at Ser55, 65, and/or 73. several observations demonstrate that the phosphorylation of BIMEL is a physiologically important mechanism for enhancing its proapoptotic activity.

SIGNOR-250134

Q15256

P49023

1

dephosphorylation

down-regulates activity

0.2

Here, we show that paxillin is a direct substrate of PTPRT and that PTPRT specifically regulates paxillin phosphorylation at tyrosine residue 88 (Y88) in colorectal cancer (CRC) cells. We engineered CRC cells homozygous for a paxillin Y88F knock-in mutant and found that these cells exhibit significantly reduced cell migration and impaired anchorage-independent growth,

SIGNOR-248720

P49840

O15084

1

phosphorylation

down-regulates activity

0.2

We provide evidence for a dual kinase-mediated regulation of the PITK holoenzyme whereby PITK phosphorylation at S1017 is catalyzed by calcium/calmodulin-dependent kinase II-delta (CaMKIIdelta), promoting the subsequent phosphorylation of S1013 by glycogen synthase kinase-3 (GSK3) in vitro.|the phosphorylation of PITK at these specific residues altered PP1 binding and subsequent PITK-directed dephosphorylation of hnRNP K

SIGNOR-264792

Q92643

Q96S52

2

binding

up-regulates activity

0.943

To determine roles for PIG-S and PIG-T, we disrupted these genes in mouse F9 cells by homologous recombination. PIG-S and PIG-T knockout cells were defective in transfer of GPI to proteins, particularly in formation of the carbonyl intermediates. We also demonstrate that PIG-S and PIG-T form a protein complex with GAA1 and GPI8, and that PIG-T maintains the complex by stabilizing the expression of GAA1 and GPI8.

SIGNOR-261362

O96013

Q15139

0

phosphorylation

up-regulates activity

0.252

When PKD3 was knocked-down using isoform-specific shRNA (PKD3-shRNA), PAK4 activity (judged by its phosphorylation status at the activation loop using the pS474-PAK4 antibody) was decreased

SIGNOR-275930

P60953

P12931

0

phosphorylation

up-regulates

0.695

Epidermal growth factor-dependent regulation of cdc42 is mediated by the src tyrosine kinaseegf signaling through src appears to have dual regulatory effects on cdc42: 1). it leads to the activation of cdc42 as mediated by the vav2 guanine nucleotide exchange factor, and 2). it results in the phosphorylation of cdc42, which stimulates the binding of rhogdi, perhaps to direct the movement of cdc42 to a specific cellular site to trigger a signaling response, because cdc42-rhogdi interactions are essential for cdc42-induced cellular transformation.

SIGNOR-118206

Q14289

Q05397

1

phosphorylation

up-regulates

0.524

Activated rock phosphorylates fak on ser732, which is essential for phosphorylation of tyr407 and for cell migration. We further show that pyk2 is activated by vegf-induced clustering of integrin v 3 and is responsible for the phosphorylation of tyr407.

SIGNOR-147070

P55211

P98170

2

binding

down-regulates quantity by destabilization

0.922

A conserved XIAP-interaction motif in caspase-9 and Smac/DIABLO regulates caspase activity and apoptosis

SIGNOR-105702

P42336

P63215

2

binding

up-regulates

0.385

Gbetagamma subunits released from gi can activate pi3k (phosphoinositide 3-kinase), and can be therefore implicated in smo-dependent activation of akt

SIGNOR-145125

P43686

Q92630

0

phosphorylation

down-regulates quantity by destabilization

0.284

Through a kinome-wide screen, we have identified dual-specificity tyrosine-regulated kinase 2 (DYRK2) as the primary kinase that phosphorylates Rpt3-Thr25, leading to enhanced substrate translocation and degradation.

SIGNOR-275845

Q16539

Q15717

1

phosphorylation

up-regulates

0.523

P38 mapk phosphorylates the mrna binding protein hur on thr118, which results in cytoplasmic accumulation of hur and its enhanced binding to the p21cip1 mrna.

SIGNOR-186135

Q4VCS5

Q9H0M0

0

ubiquitination

up-regulates quantity by stabilization

0.275

Here low serum and high LATS1 activity are found to enhance the levels of the 130-kDa isoform of angiomotin (Amot130) through phosphorylation by LATS1/2 at serine 175, which then forms a binding site for 14-3-3. Such phosphorylation, in turn, enables the ubiquitin ligase atrophin-1 interacting protein (AIP)4 to bind, ubiquitinate, and stabilize Amot130

SIGNOR-275847

Q8IZL8

Q9NU22

2

binding

up-regulates quantity by stabilization

0.377

MDN1 Is Physically and Functionally Associated with the Mammalian PELP1 Complex. To more specifically determine a function of mammalian MDN1 in the subnuclear distribution of PELP1-containing pre-60S-particles, we examined PELP1 localization in control cells or cells depleted from MDN1. Importantly, in the absence of MDN1, PELP1 became sequestered in enlarged nucleoli, indicating that MDN1 is involved in the nucleolar release of PELP1-containing pre-60S ribosomes

SIGNOR-261357

P29350

P23458

1

dephosphorylation

down-regulates

0.646

We find, for the first time, that shp-1 down-regulates the level of tyk2 kinase in h9 cells and of jak1 kinase in htb26 cells, by accelerating their degradation.

SIGNOR-119197

P49841

P56693

1

phosphorylation

down-regulates quantity

0.406

Besides, GSK3\u03b2 phosphorylates SOX10 at CPD domain and facilitates Fbxw7\u03b1-mediated SOX10 degradation.|Besides, GSK3beta phosphorylates SOX10 at CPD domain and facilitates Fbxw7alpha mediated SOX10 degradation.

SIGNOR-279617

Q9UM73

2

phosphorylation

up-regulates activity

0.2

ALK SelectiVely Phosphorylates the First Tyrosine in Its A-Loop Peptide.

SIGNOR-250575

O95837

P28222

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-257207

P37840

P48729

0

phosphorylation

up-regulates

0.371

In vitro experiments and two-dimensional phosphopeptide mapping provided further evidence that serine 129 was phosphorylated by ck-1 and ck-2. Moreover, phosphorylation of serine 129 was reduced in vivo upon inhibition of ck-1 or ck-2. These data demonstrate that alpha-synuclein is constitutively phosphorylated within its c terminus and may indicate that the function of alpha-synuclein is regulated by phosphorylation/dephosphorylation.From these data we conclude that _-synuclein is predominantly phosphorylated at serine residue 129. However, a second serine at position 87 is also used for phosphorylation to some extent. together, these data may indicate that ck-1 and ck-2 are involved in the regulation of neuronal function and one may speculate that phosphorylation of _-synuclein could affect its binding to membranes.

SIGNOR-73799

Q96G91

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-256931

Q15303

P35070

2

binding

up-regulates

0.723

For example, betacellulin binds to and activates both erbb1 and erbb4, whereas epiregulin binds to erbb1, erbb3 and erbb4

SIGNOR-195347

Q9Y297

O15534

1

ubiquitination

down-regulates

0.57

We have found that per1 interacts with both _-trcp1 and _-trcp2 in a manner that depends on casein kinase 1 activity, and depletion of both _-trcp1 and _-trcp2 by rnai leads to dramatic stabilization of per1

SIGNOR-137755

P08575

P06241

1

dephosphorylation

up-regulates activity

0.73

On the membrane SKAP55, via its phosphorylated Tyr-271, further binds the SH2 domain of Fyn to replace the low-affinity bound inhibitory site of the kinase. Consequently, CD45 may have transiently disassociated with the Tyr-232 residue of SKAP55 through dephosphorylation and simultaneously interacted with the released the phosphorylated inhibitory tyrosine residue of Fyn for dephosphorylation, resulting in activation of the Src family kinase Fyn and initiation of TCR-engaged signal transduction.

SIGNOR-248352

P35222

Q9ULB5

2

binding

up-regulates activity

0.568

At its C-terminus, cadherin interacts with Î²-catenin, which dynamically associates with Î±-catenin, a direct binding partner of filamentous actin

SIGNOR-265869

P30550

P38405

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-256917

P00533

P28482

0

phosphorylation

down-regulates activity

0.639

A growth factor-stimulated protein kinase activity that phosphorylates the epidermal growth factor (EGF) receptor at Thr669 has been described Anion-exchange chromatography demonstrated that this protein kinase activity was accounted for by two enzymes. The first peak of activity eluted from the column corresponded to the microtubule-associated protein 2 (MAP2) kinase

SIGNOR-20545

Q03113

Q9HC97

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-257204

P13288

Q14653

1

phosphorylation

down-regulates activity

0.2

BGLF4 kinase interacts physically with and phosphorylates IRF3, which is the initial activator of transcription in the innate immune response. BGLF4 suppresses IRF3-dependent transcriptional activation. Data here suggest that Ser123, Ser173, and Thr180 contribute additively to the BGLF4-mediated repression of the IRF3 transactivation activity.

SIGNOR-266647

Q6PGQ7

P49841

0

phosphorylation

up-regulates

0.258

It suggests that gsk3_ activity is required for hbora-mediated mitotic entry through ser274 and ser278 phosphorylation

SIGNOR-201519

P41221

Q01974

2

binding

up-regulates

0.775

Wnt5a induces ROR1/ROR2 heterooligomerization to enhance leukemia chemotaxis and proliferation|Evolutionarily conserved receptor tyrosine kinase–like orphan receptor-1 and -2 (ROR1/2) are considered distinct receptors for Wnt5a and are implicated in noncanonical Wnt signaling in organogenesis and cancer metastasis.

SIGNOR-199647

Q9BYT3

Q5JQC9

1

phosphorylation

up-regulates quantity by stabilization

0.2

Differential phosphoproteomic analysis and in vitro kinase assay identified novel phosphorylation substrates of STK33, fibrous sheath components AKAP3 and AKAP4, whose expression levels decreased in testis after deletion of Stk33.

SIGNOR-272956

P63092

Q03431

2

binding

up-regulates activity

0.506

This calciotropic hormone exerts its actions via binding to the PTH/PTH-related peptide receptor (PTH1R), which couples to multiple heterotrimeric G proteins, including Gs and Gq/11.

SIGNOR-270551

P49761

Q07955

1

phosphorylation

up-regulates activity

0.531

In vitro, Clk/Sty efficiently phosphorylated the SR family member ASF/SF2 on serine residues located within its serine/arginine-rich region (the RS domain). Overexpression of the active Clk/Sty kinase caused a redistribution of SR proteins within the nucleus. These results suggest that Clk/Sty kinase directly regulates the activity and compartmentalization of SR splicing factors.

SIGNOR-273859

Q15172

Q01484

0

relocalization

up-regulates quantity

0.282

Ankyrin-B is targeted to the M-line via its interaction with the C-terminal domain of the large sarcomeric protein obscurin. Obscurin is targeted to the M-line via its N-terminal interactions with myomesin and titin. This population of ankyrin-B recruits B56α, a regulatory subunit of protein phosphatase 2A, to the M-line where the phosphatase may regulate the phosphorylation status of contractile and signalling proteins.

SIGNOR-266729

Q13207

P23760

0

transcriptional regulation

up-regulates quantity by expression

0.346

We have recently found that a T-box gene family member, TBX2, is highly overexpressed in both ERMS and ARMS cells (Zhu et al, 2014). The regulation of TBX2 is uncharacterised in RMS cells, but is likely to link TBX2 expression to the known deregulation of signalling pathways in RMS. In melanoma cells, TBX2 is regulated by PAX3

SIGNOR-249596

Q92830

P68431

1

acetylation

down-regulates activity

0.2

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

SIGNOR-269602

P62136

P42575

1

dephosphorylation

up-regulates activity

0.2

nutrient-replete oocytes inhibit C2 via S135 phosphorylation catalyzed by calcium/calmodulin-dependent protein kinase II. We now show that C2 phosphorylated at S135 binds 14-3-3zeta, thus preventing C2 dephosphorylation. Moreover, we determined that S135 dephosphorylation is catalyzed by protein phosphatase-1 (PP1), which directly binds C2.

SIGNOR-248564

P17861-2

Q96EB6

0

deacetylation

down-regulates activity

0.379

P300 increases the acetylation and protein stability of XBP1s, and enhances its transcriptional activity, whereas SIRT1 deacetylates XBP1s and inhibits its transcriptional activity.. The mRNA encoding the active spliced form of XBP1 (XBP1s) is generated from the unspliced form by IRE1 (inositol-requiring enzyme 1) during the UPR.

SIGNOR-260430

Q12864

P35222

2

binding

up-regulates activity

0.705

At its C-terminus, cadherin interacts with Î²-catenin, which dynamically associates with Î±-catenin, a direct binding partner of filamentous actin

SIGNOR-265856

Q03135

P06241

0

phosphorylation

down-regulates activity

0.721

Caveolin-1 is phosphorylated on tyr(14) in response to both oxidative and hyperosmotic stress. In the present paper, we show that this phosphorylation requires activation of the src family kinase fyn.Therefore,

SIGNOR-118003

Q08378

Q16584

0

phosphorylation

up-regulates activity

0.361

In vitro kinase assays demonstrated that MLK3 directly phosphorylates golgin-160 in the N-terminal head region between residues 96 and 259.

SIGNOR-279065

P51451

P12318

1

phosphorylation

up-regulates activity

0.436

To identify the FcgammaRII-phosphorylating protein tyrosine kinase (PTK), we used the combination of an in vitro and an in vivo approach. In an in vitro assay using recombinant cytoplasmic tails of the different FcgammaRII isoforms as well as tyrosine exchange mutants, we show that each of the BCR-associated PTKs (Lyn, Blk, Fyn, and Syk) shows different phosphorylation patterns with regard to the different FcgammaR isoforms and point|Fyn and Blk definitely phosphorylate Y-282 in the ITAM of Fc_RIIa/c, whereas the non-ITAM tyrosine residue (Y-275) becomes phosphorylated by Syk, as the phosphorylation of double point mutants shows. In addi-tion to these tyrosine residues, Fyn, Blk, and Syk might phosphorylate the most C-terminal tyrosine residue (Y-298) because altering this tyrosine residue together with one of the tyrosine residues clearly shown to be phosphorylated by the respective PTK results in the abrogation of phosphorylation.

SIGNOR-249312

Q9NQS7

Q96GD4

2

binding

up-regulates

0.974

Using recombinant proteins, we found that aurora b kinase activity was stimulated by incenp and that the c-terminal region of incenp was sufficient for activation.

SIGNOR-86218

P52945

O43791

0

ubiquitination

down-regulates quantity

0.326

Pdx1 C terminus-interacting factor-1 (Pcif1, also known as SPOP) is a nuclear protein that inhibits Pdx1 transactivation. Here, we show that Pcif1 targets Pdx1 for ubiquitination and proteasomal degradation.

SIGNOR-268859

P23771

Q99835

0

null

up-regulates activity

0.2

That GATA is a downstream effector of the hedgehog pathway.

SIGNOR-253527

Q9H4X1

P06493

2

binding

up-regulates activity

0.53

RGC-32 was physically associated with cyclin-dependent kinase p34CDC2 and increased the kinase activity in vivo and in vitro. In addition, RGC-32 was phosphorylated by p34CDC2-cyclin B1 in vitro. Mutation of RGC-32 protein at Thr-91 prevented the p34CDC2-mediated phosphorylation and resulted in loss of p34CDC2 kinase enhancing activity.

SIGNOR-262726

P68400

P20042

1

phosphorylation

up-regulates

0.35

The n-terminal domain of the human eif2beta subunit and the ck2 phosphorylation sites are required for its function. These results suggest that ser2 and ser67 contribute to the important role of the n-terminal region of eif2beta for its function in mammals.

SIGNOR-140994

Q05682

Q00535

0

phosphorylation

down-regulates quantity by destabilization

0.341

Together, these data demonstrate that phosphorylation of caldesmon on Ser527 by Cdk5 serves to down regulate its stability.

SIGNOR-280215

Q96BR9

Q8TBB1

0

polyubiquitination

down-regulates quantity by destabilization

0.2

LNX (ligand of Numb protein-X) is a RING finger and four PDZ domain-containing E3 ubiquitin ligase. Lnx-l induced K48-linked polyubiquitylation of Boz, leading to its proteasomal degradation in human 293T cells and in zebrafish embryos.

SIGNOR-272777

P52757

P06239

0

phosphorylation

down-regulates activity

0.2

We now demonstrate Lck-dependent phosphorylation of beta2-chimaerin in response to TCR triggering. We identify Tyr-153 as the Lck-dependent phosphorylation residue and show that its phosphorylation negatively regulates membrane stabilization of beta2-chimaerin, decreasing its GAP activity to Rac.

SIGNOR-276240

Q12798

O43303

2

binding

up-regulates activity

0.483

We report that CP110 interacts with two different Ca2+-binding proteins, calmodulin (CaM) and centrin, in vivo. our data demonstrate a functional role for CaM binding to CP110 and suggest that CP110 cooperates with CaM and centrin to regulate progression through cytokinesis.

SIGNOR-265966

P04792

Q05655

0

phosphorylation

down-regulates activity

0.515

Radioactive kinase assays confirmed that PKC\u03b4 phosphorylated Hsp27 at Ser78 and Ser82 ( Fig. 3 B).

SIGNOR-278425

O94901

Q3KP22

2

binding

up-regulates activity

0.2

In this study, we found that SUN1 not only interacted with TERB1 but also interacted with MAJIN, and the interaction of SUN1 with MAJIN is stronger than TERB1. We also found that SUN1 interacted with SPDYA, an activator of CDK2. | It will be of great interest to test this hypothesis to fully understand the mechanisms of stable telomere–NE connection and telomere movement along the NE driven by the LINC complex.

SIGNOR-263300