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
O60729	Q13309	1	dephosphorylation	down-regulates quantity by destabilization	0.357	The activity of SCF(Skp2) is regulated by the Cyclin-dependent kinase (CDK)2-mediated phosphorylation of Skp2 on Ser64 allows its expression in mid-G1 phase, even in the presence of active APC(Cdh1). Reciprocally, dephosphorylation of Skp2 by the mitotic phosphatase Cdc14B at the M --> G1 transition promotes its degradation by APC(Cdh1).	SIGNOR-248333
Q9UQ26	A6NJZ7	2	binding	down-regulates activity	0.265	SH3 domains of RBPs interact with RIMs. The enhancement of depolarization-induced secretion in PC12 cells by fusion proteins that suppress the associations of RBPs with RIMs and α1 suggests that RBPs may repress RIMs, either directly or through associated proteins.	SIGNOR-264367
Q9H992	P10636	1	ubiquitination	down-regulates activity	0.2	We have identified and characterized axotrophin, a protein that binds and preferentially mono-ubiquitinates tau protein.	SIGNOR-278655
Q99708	P14618	0	phosphorylation	up-regulates activity	0.2	Here, we uncover an unexpected mechanism through which pyruvate kinase M2 (PKM2), the highly expressed PK isoform in cancer cells and a master regulator of cancer metabolic reprogramming, integrates with the DDR to directly promote DNA double-strand break (DSB) repair. In response to ionizing radiation and oxidative stress, ATM phosphorylates PKM2 at T328 resulting in its nuclear accumulation.	SIGNOR-277413
Q13547	O95471	1	transcriptional regulation	down-regulates quantity by repression	0.2	ChIP assays revealed that SNAI1P is recruited on the CLDN7 gene promoter along with the co-repressor CtBP1 and the effector HDAC1.\|These data further suggest that HDAC1 is involved in the SNAI1P-mediated repression of the human CLDN7 gene promoter.	SIGNOR-254106
Q15256	Q16539	1	dephosphorylation	down-regulates	0.558	As shown, gst-ptp-sl dephosphorylated efficiently both erk2 and p38 wild typetogether, these results indicate that the defective association of the tyrosine phosphatase ptp-sl with erk2 d319n and p38 d316n mutations impairs the retention and inactivation in the cytosol of these map kinases by ptp-sl.	SIGNOR-111762
Q9H3K2	P99999	1	relocalization	down-regulates quantity	0.255	MICS1 was clearly coprecipitated with cytochrome c-3FLAG and the amount was DSP concentration-dependent (Figure 6A). Together with the finding that overexpression of exogenous MICS1 delayed the apoptotic release of cytochrome c in normal-serum level medium (Figure 4A), these results suggest that MICS1 helps to retain cytochrome c in the inner membrane, apart from the morphological changes.	SIGNOR-260294
O15360	Q13535	0	phosphorylation	up-regulates	0.598	The s1449a mutant failed to completely correct a variety of fa-associated phenotypes. The dna damage response is coordinated by phosphorylation events initiated by apical kinases atm (ataxia telangectasia mutated) and atr (atm and rad3-related), and atr is essential for proper fa pathway function. Serine 1449 is in a consensus atm/atr site	SIGNOR-182953
Q15185	P07900	2	binding	up-regulates activity	0.916	The mutant Hsp90 proteins tested are defective in the binding and ATP hydrolysis-dependent cycling of the co-chaperone p23, which is thought to regulate the binding and release of substrate polypeptide from Hsp90.	SIGNOR-262831
P08151	Q15915	0	relocalization	up-regulates	0.377	Co-expression of zic1 resulted in gli1 and gli3 proteins being translocated to the nucleus in varying levels	SIGNOR-105491
P68400	O15259	1	phosphorylation	up-regulates	0.2	Casein kinase 2 (ck2)-mediated phosphorylation of three critical serine residues within a cluster of acidic amino acids in nephrocystin mediates pacs-1 binding, and is essential for colocalization of nephrocystin with pacs-1 at the base of cilia. Inhibition of ck2 activity abrogates this interaction and results in the loss of correct nephrocystin targeting.	SIGNOR-142343
Q15465	Q9Y6C5	2	binding	down-regulates activity	0.803	Biochemical analysis of ptch and ptch2 shows that they both bind to all hedgehog family members with similar affinity and that they can form a complex with smo.Current models suggest that binding of Shh to PTCH prevents the normal inhibition of the seven-transmembrane-protein Smoothened (SMO) by PTCH.	SIGNOR-217776
Q15797	P36894	0	phosphorylation	up-regulates activity	0.732	Two types of bmp-induced signaling pathways are known, the smad and p38 mapk pathways. In the former case, bmpr1 phosphorylates smad-1,-5,-8, which forms a complex with smad4 that translocates into the nucleus and regulates gene expression.	SIGNOR-255263
P12931	Q16825	0	dephosphorylation	up-regulates	0.643	Ptpd1 activates src tyrosine kinase and increases the magnitude and duration of epidermal growth factor (egf) signaling.	SIGNOR-124774
P63096	P35408	2	binding	up-regulates activity	0.312	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-257032
P37802	O94921	0	phosphorylation	down-regulates activity	0.315	This newly identified oncogene–tumor suppressor cascade, where oncogenic PFTK1 inactivates a tumor suppressor gene TAGLN2 via phosphorylation\|. Our data therefore underline much importance for S83 and S163 residues on TAGLN2 in its actin-binding capacity.	SIGNOR-265103
Q99677	P08754	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-257170
O14974	Q9H093	0	phosphorylation	down-regulates activity	0.466	NUAK2 phosphorylates and inhibits MYPT1, the regulatory subunit of MLC phosphatase, stabilizing actin filaments and mediating contraction of smooth muscle cells ( xref ).	SIGNOR-279081
Q7Z2K8	P51608	0	post transcriptional regulation	up-regulates quantity by expression	0.298	MeCP2 binds to the promoter region of six target genes. ChIP with anti-MeCP2 antibody shows that MeCP2 binds to the promoter regions of activated targets Sst, Oprk1, Gamt, and Gprin1, and repressed targets Mef2c and A2bp1.	SIGNOR-264679
P68400	P18887	1	phosphorylation	up-regulates	0.395	Xrcc1 phosphorylation by ck2 is required for its stability and efficient dna repair	SIGNOR-165419
Q92993	P62805	1	acetylation	down-regulates activity	0.2	Thus, the TIP60 HAT complex is recruited to MYC-target genes and, probably with other other HATs, contributes to histone acetylation in response to mitogenic signals.	SIGNOR-262061
Q13131	Q8N122	1	phosphorylation	down-regulates activity	0.687	Ampk in turn inactivates mtorc1 directly by phosphorylating raptor and indirectly by phosphorylating tsc2.	SIGNOR-173035
P06241	P18433	0	dephosphorylation	up-regulates	0.658	Ptpalpha is a more widely expressed transmembrane ptp that has been shown to regulate the src family kinases, src and fyn, and is also present in t cells.	SIGNOR-154796
P36894	O95476	2	binding	up-regulates	0.291	We show that dullard promotes the ubiquitin-mediated proteosomal degradation of bmp receptors (bmprs). Dullard preferentially complexes with the bmp type ii receptor (bmprii) and partially colocalizes with the caveolin-1-positive compartment, suggesting that dullard promotes bmpr degradation via the lipid raft-caveolar pathway	SIGNOR-150998
Q8NA31	O94901	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-263299
P51813	Q96T51	1	phosphorylation	up-regulates activity	0.634	Etk interacts with RUFY1 through its SH3 and SH2 domains. RUFY1 is tyrosine-phosphorylated and appears to be a substrate of Etk. Phosphorylation of the two tyrosine residues, Tyr-281 and Tyr-292, located in the linker region of the two coiled-coil domains by Etk seems to be critical for RUFY1 targeting to the endosomes.	SIGNOR-262679
P28482	Q13362	2	phosphorylation	down-regulates	0.513	Iex-1 binds to b56 subunits and perk independently, enhances b56 phosphorylation by erk at a conserved ser/pro site in this complex and triggers dissociation from the catalytic subunit.	SIGNOR-144313
Q92918	P46109	2	binding	up-regulates	0.587	We found that hpk1 interacted with crk and crkl adaptor proteins in vitro and in vivo and that the proline-rich motifs within hpk1 were involved in the differential interaction of hpk1 with the crk proteins and grb2. Crk and crkl not only activated hpk1 but also synergized with hpk1 in the activation of jnk.	SIGNOR-63991
O15111	Q9Y243	0	phosphorylation	up-regulates	0.414	Although there are likely to be multiple levels of crosstalk between the pi3k-akt and nf-kb pathways, one mechanism has been attributed to direct phosphorylation of the amino acid residue t23 on ikb kinase alfa (ikkalfa) by akt, thereby leading to activation of this kinase upstream of nf-kb akt mediates ikkalpha phosphorylation at threonine 23 akt transiently associates in vivo with ikk and induces ikk activation. Akt mediates ikkalfa phosphorylation at threonine 23.Akt phosphorylates ikkalpha on t23, and this phosphorylation event is a prerequisite for the phosphorylation of p65 at s534 by ikkalpha and beta	SIGNOR-187062
Q01082	Q12955	2	binding	up-regulates activity	0.644	Ankyrin-G is a molecular partner of E-cadherin in epithelial cells and early embryos. Ankyrin-G also recruits beta-2-spectrin to E-cadherin-beta-catenin complexes, thus providing a direct connection between E-cadherin and the spectrin/actin skeleton.	SIGNOR-266711
P48382	P01903	1	transcriptional regulation	up-regulates quantity by expression	0.503	In this report, we correlate the loss of IFN-γ induction of MHC class II genes with the identification of a molecular defect in an essential regulator, namely RFX5. \| We have further confirmed this finding by showing that new RFX5 leucine mutants created in vitro are incapable of transactivating a class II promoter, suggesting the identification of residues essential for RFX activity.	SIGNOR-266228
P40763	Q5VWQ8	2	binding	down-regulates activity	0.346	DAB2IP could interact with the signal transducer and activator of transcription 3 (STAT3) via its unique PR domain and suppress STAT3 phosphorylation and transactivation, leading to the inhibition of survivin expression in PCa cells.	SIGNOR-254761
P51955	Q07955	1	phosphorylation	down-regulates activity	0.385	First, NEK2 interacts with and phosphorylates SRSF1.	SIGNOR-279344
P07949	P78527	1	phosphorylation	up-regulates activity	0.27	Phosphorylation of DNA-PKcs at s2056 is elevated in RET expressing cells and can be reduced by RET inhibition.	SIGNOR-279275
P45983	Q07817	1	phosphorylation	down-regulates	0.775	By site-directed mutagenesis studies, we have identified that serine 62 is the necessary site for taxol- or 2-me-induced bcl-xl phosphorylation in prostate cancer cells. Further studies with the inhibitor of jun kinase (jnk) and phosphorylation mutant of bcl-xl reveal the augmentative role of jnk-mediated bcl-xl phosphorylation in apoptosis of prostate cancer cells. In summary, our studies suggest that the phosphorylation of bcl-xl by stress response kinase signaling might oppose the anti-apoptotic function of bcl-xl to permit prostate cancer cells to die by apoptosis	SIGNOR-99219
O15550	Q05516	1	transcriptional regulation	up-regulates quantity by expression	0.311	UTX catalytic activity has been reported to upregulate expression of the master transcription factor PLZF and to modulate superenhancer accessibility in invariant natural killer T cells.	SIGNOR-260038
P53350	O43524	1	phosphorylation	down-regulates activity	0.491	Furthermore, PLK1 can directly phosphorylate FOXO3 in an in vitro kinase assay.\|PLK1 induces translocation of FOXO3 from the nucleus to the cytoplasm and suppresses FOXO3 activity, measured by the decrease in the pro-apoptotic Bim protein levels and in the cell cycle inhibitor protein p27.	SIGNOR-279095
P52333	Q9HBE5	2	binding	up-regulates	0.558	Retroviral-mediated transduction of wild-type gamma c into xscid jt cells restored function to the il-21r, as shown by il-21-induced tyrosine phosphorylation of jak1 and jak3, and downstream activation of stat5	SIGNOR-90269
P53396	P17612	0	phosphorylation	up-regulates activity	0.309	Phosphorylation of Recombinant Human ATP:Citrate Lyase by cAMP-Dependent Protein Kinase Abolishes Homotropic Allosteric Regulation of the Enzyme by Citrate and Increases the Enzyme Activity. Ser 454, which is phosphorylated by the catalytic subunit of cAMP-dependent protein kinase (PKA)	SIGNOR-250328
P00533	P15941	1	phosphorylation	up-regulates activity	0.577	We also show that the activated egf-r phosphorylates the muc1 cytoplasmic tail on tyrosine at a yekv motif that functions as a binding site for the c-src sh2 domain. The results demonstrate that egf-r-mediated phosphorylation of muc1 induces binding of muc1 to c-src in cells	SIGNOR-109538
Q14493	Q6NXT2	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-265420
Q7Z434	Q14653	2	binding	up-regulates activity	0.8	Phosphorylated MAVS and STING then bind to a positively charged surface of interferon regulatory factor 3 (IRF3) and thereby recruit IRF3 for its phosphorylation and activation by TBK1.	SIGNOR-260143
P68400	O95863	1	phosphorylation	up-regulates quantity by stabilization	0.348	Serines 11 and 92 participate in the control of snail1 stability and positively regulate snail1 repressive function and its interaction with msin3a corepressor. Furthermore, serines 11 and 92 are required for snail1-mediated emt and cell viability, respectively. Pka and ck2 have been characterized as the main kinases responsible for in vitro snail1 phosphorylation at serine 11 and 92, respectively.	SIGNOR-161771
P53805	P28482	0	phosphorylation	up-regulates activity	0.27	Consensus phosphorylation sites for p42/44 MAPK and GSK-3 are present in the SP repeat of MCIP1 at serine 112 and serine 108, respectively \|Several endogenous proteins are capable of inhibiting the catalytic activity of calcineurin. Modulatory calcineurin interacting protein 1 (MCIP1) is unique among these proteins on the basis of its pattern of expression and its function in a negative feedback loop to regulate calcineurin activity. Here we show that MCIP1 can be phosphorylated by MAPK and glycogen synthase kinase-3 and that phosphorylated MCIP1 is a substrate for calcineurin.	SIGNOR-249198
Q969V1	Q03113	2	binding	up-regulates activity	0.25	Here we systematically quantified ligand-induced interactions between 148 GPCRs and all 11 unique G alpha subunit C-termini. For each receptor, we probed chimeric G alpha subunit activation via a transforming growth factor-alpha (TGF alpha) shedding response in HEK293 cells lacking endogenous Gq/11- and G12/13- signaling. \| We defined positive coupling if any member of the subfamily scored LogRAi ≥ -1 and negative coupling if all of the members scored LogRAi < -1 (Figure 3A-B). ROC analysis gives AUC = 0.78 (Figure S4A) when considering high-confidence known coupling data and suggested a threshold of LogRAi ≥ -1.0 for defining true couplings. \| The score associated to this interaction has a LogRAi ≥ -1.0.	SIGNOR-257439
P55011	Q9BYP7	0	phosphorylation	up-regulates activity	0.525	We have shown that with-no-lysine kinase 3 (WNK3) possesses several properties that suggest it could be the Cl−/volume-sensitive regulatory kinase that, in association with protein phosphatases, reciprocally modifies the phosphorylation/dephosphorylation states of the SLC12 proteins and thus their activities\|WNK3 activates NKCC1/2 and NCC and inhibits the KCCs	SIGNOR-264625
P10523	Q93034	2	binding	up-regulates quantity by stabilization	0.412	Here we report that NEDD4-1, a HECT domain-containing E3 ubiquitin ligase, binds via its HECT domain directly with SAG's C-terminal RING domain and ubiquitylates SAG for proteasome-mediated. We also found that SAG bridges NEDD4-1 via its C-terminus and CUL-5 via its N-terminus to form a NEDD4-1/SAG/CUL-5 tri-complex. Biologically, NEDD4-1 overexpression sensitizes cancer cells to etoposide-induced apoptosis by reducing SAG levels through targeted degradation. Thus, SAG is added to a growing list of NEDD4-1 substrates and mediates its biological function. degradation.	SIGNOR-272844
P19525	O75569	1	phosphorylation	up-regulates activity	0.796	In stressed cells, this activation occurs when PACT, a PKR-binding protein, is phosphorylated and activates PKR.	SIGNOR-280003
P20393	P35398	2	binding	down-regulates activity	0.461	Direct Regulation of the NPAS2 Promoter by RORα and REV-ERBα. it appears in the context of the NPAS2 promoter RORα functions as a transcriptional activator, but REV-ERBα may only function as an inhibitor of RORα activity by blocking binding.	SIGNOR-267979
O43524	Q14680	0	phosphorylation	down-regulates quantity	0.362	Further analysis indicated that FOXO1 and FOXO3, two known transcriptional regulators of p21, were phosphorylated by MELK and thus be involved in the induction of p21 after MELK inhibition.\|Our findings revealed that siRNA mediated MELK knockdown increased protein levels of FOXO1 and FOXO3, which might increase p21 transcriptional level in a p53 independent manner.	SIGNOR-279375
P23470	P10721	1	dephosphorylation	down-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-254710
P37173	O00459	2	binding	up-regulates	0.433	These studies revealed that PI 3-kinase is associated in vivo with both TGF-_ receptor subtypes and that TGF-_1 stimulation enhances PI 3-kinase activity associated with type I TGF-_ receptor in hASM cells.	SIGNOR-227528
P16473	Q96T91	2	binding	up-regulates	0.546	Recombinant a2/b5 heterodimeric glycoproteins, purified using cation exchange and size fractionation chromatography, activated human tsh receptors, but not lh and fsh receptors, and showed high affinity to tsh receptors in a radioligand receptor assay	SIGNOR-88614
P06493	Q13286	1	phosphorylation	down-regulates activity	0.257	(D) Phosphorylation of Cln3 by Cdk1 is independent of Ssa1 T36.\|Thereby, both Cdk1 and Pho85can promote Cln3 degradation, though under distinct circumstances.	SIGNOR-279013
O00220	Q13158	2	binding	up-regulates	0.831	Fadd binds to ligated trailr1 or trail-r2	SIGNOR-97869
Q01668	P17612	0	phosphorylation	up-regulates activity	0.396	We recently demonstrated that PKA activation led to increased alpha(1D) Ca(2+) channel activity in tsA201 cells by phosphorylation of the channel protein. Western blotting showed that the N terminus and C terminus were phosphorylated. Serines 1743 and 1816, two PKA consensus sites, were phosphorylated by PKA and identified by mass spectrometry.	SIGNOR-263109
P46527	P06493	2	binding	down-regulates	0.655	P21 and p27 are key inhibitors of both cdk1 and cdk2.	SIGNOR-128445
Q15561	P46937	2	binding	up-regulates activity	0.927	The multifunctional cytokine TGF-β has been identified as a potent inducer of CTGF expression, activating CTGF transcription through the canonical Smad signaling pathway. It is worth noting that TGF-β synergizes with Hippo–Yes-associated protein (YAP) signaling, a key regulator of tumorigenesis, to induce the expression of CTGF by the formation of a YAP-TEAD4-Smad3-p300 complex on the CTGF promoter	SIGNOR-277685
P46060	P68400	0	phosphorylation	up-regulates	0.31	Phosphorylation of rangap1 stabilizes its interaction with ran and ranbp1. Serine-358 (358s) was identified as the major phosphorylation site. Experiments using purified recombinant kinase and specific inhibitors such as drb and apigenin strongly suggest that casein kinase ii (ck2) is the responsible kinase	SIGNOR-143948
Q9Y463	P13807	1	phosphorylation	down-regulates activity	0.258	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-260633
P49841	Q96R06	1	phosphorylation	up-regulates	0.271	Astrin acts as a substrate for gsk3beta and is phosphorylated at thr-111, thr-937 ((s/t)p motif) and ser-974/thr-978 ((s/t)xxx(s/t)-p motif;p is a phosphorylatable residue). Inhibition of gsk3beta impairs spindle and kinetochore accumulation of astrin and spindle formation at mitosis, suggesting that astrin association with the spindle microtubule and kinetochore may be dependent on phosphorylation by gsk3beta	SIGNOR-159578
P32245	P01189	2	binding	up-regulates activity	0.778	The melanocortin (MC) receptor family consists of five Gs-coupled receptors that control various physiological functions in response to four distinct agonists, adrenocorticotropic hormone (ACTH, also known as corticotrophin) and alpha, beta, and gamma melanocyte-stimulating hormone (MSH), which are derived from the proopiomelanocortin precursor protein, and two inverse agonists, agouti and agouti-related proteins	SIGNOR-268710
Q16611	Q9BXH1	2	binding	up-regulates	0.382	Bim, and puma bind with high affinity to all pro-survival proteins	SIGNOR-196929
P48506	Q16236	0	transcriptional regulation	up-regulates quantity by expression	0.47	In both models, the inducer-modified and Nrf2-bound Keap1 is inactivated and, consequently, newly synthesized Nrf2 proteins bypass Keap1 and translocate into the nucleus, bind to the ARE and drive the expression of Nrf2 target genes such as NAD(P)H quinone oxidoreductase 1 (NQO1), heme oxygenase 1 (HMOX1), glutamate-cysteine ligase (GCL) and glutathione S transferases (GSTs).	SIGNOR-256277
Q8TDQ0	Q08881	0	phosphorylation	up-regulates activity	0.31	When we tested the effect of ITK on the Y265 mutant, we found a pronounced reduction of ITK-mediated tyrosine phosphorylation, suggesting that Y265 is specifically phosphorylated by ITK (Fig. 3B). Our results demonstrate that specific phosphorylation of Y265 of Tim-3 occurs in the presence of galectin-9, probably through a receptor-ligand interaction. Phosphorylation of Y265, which is situated in a highly conserved SH2 binding domain, could result in the recruitment of SH2 containing adaptor proteins and trigger downstream signalling events regulating the fate of Tim-3 expressing T-cells.	SIGNOR-273644
P13796	P17612	0	phosphorylation	up-regulates	0.327	Phosphorylation on ser5 increases the f-actin-binding activity of l-plastin and promotes its targeting to sites of actin assembly in cells. L-plastin phosphorylation require protein kinase a.	SIGNOR-146287
P81133	P27540	2	binding	up-regulates activity	0.531	We demonstrate that both SIM1 and SIM2 can heterodimerize via their helix-loop-helix·PAS regions with ARNT, but not with AHR, and that they do not form homodimers. Furthermore, SIM1 may have a dual role, both negatively affecting AHR·ARNT binding to the XRE and also acting in concert with ARNT as a novel DNA-binding heterodimer.	SIGNOR-240759
P34995	O95837	2	binding	up-regulates activity	0.435	Here we systematically quantified ligand-induced interactions between 148 GPCRs and all 11 unique G alpha subunit C-termini. For each receptor, we probed chimeric G alpha subunit activation via a transforming growth factor-alpha (TGF alpha) shedding response in HEK293 cells lacking endogenous Gq/11- and G12/13- signaling. \| We defined positive coupling if any member of the subfamily scored LogRAi ≥ -1 and negative coupling if all of the members scored LogRAi < -1 (Figure 3A-B). ROC analysis gives AUC = 0.78 (Figure S4A) when considering high-confidence known coupling data and suggested a threshold of LogRAi ≥ -1.0 for defining true couplings. \| The score associated to this interaction has a LogRAi ≥ -1.0.	SIGNOR-257194
Q14161	Q05209	0	dephosphorylation	down-regulates	0.344	Conversely, a gfp-pkl phosphorylation mutant, y286/392/592f (gfp-pkl triple yf) (brown et al., 2005), was not phosphorylated during adhesion and the addition of ptp-pest had no effect, suggesting one or more of these tyrosine residues are dephosphorylated by ptppest. Taken together, these data strongly suggest pkl as a direct substrate for ptp-pest.	SIGNOR-142719
Q9Y253	Q13535	0	phosphorylation	up-regulates	0.415	Atr-mediated phosphorylation of dna polymerase _ is needed for efficient recovery from uv damage. We show that, after uv irradiation, pol_ becomes phosphorylated at ser601 by the ataxia-telangiectasia mutated and rad3-related (atr) kinase. Atr-dependent phosphorylation of pol_ is necessary to restore normal survival and postreplication repair	SIGNOR-171290
Q16778	Q14493	0	translation regulation	up-regulates quantity by expression	0.2	Synthesis of mature histone mRNA requires only a single processing reaction: an endonucleolytic cleavage between a conserved stem-loop and a purine-rich downstream element to form the 3' end. The stem-loop binding protein (SLBP) is required for processing, and following processing, histone mRNA is transported to the cytoplasm, where SLBP participates in translation of the histone mRNA\|We used radiolabeled probes generated by PCR targeting the open reading frame (ORF) to detect histones H2A, H2B, H3, H4, and H1 and used 7SK snRNA as a loading control (Fig. 2A). The abundance of histone H2A, H2B, H3, and H4 mRNAs is reduced to 37% to 70% of control levels in the SLBP knockdown cells when compared to the C2 control.	SIGNOR-265386
Q9UNE7	O60260	2	binding	up-regulates activity	0.2	In this study, we found that CHIP promotes Parkin-mediated Pael-R ubiquitination and subsequent degradation. In vitro ubiquitination assays suggested that only a combination of both Parkin and its cofactor CHIP function as a ubiquitin ligase, which is able to sufficiently ubiquitinate Pael-R in vivo (Figure 6).	SIGNOR-272888
P68366	Q8NG68	0	tyrosination	down-regulates	0.286	Tubulin tyrosine ligase (ttl) adds a c-terminal tyr to __tubulin as part of a tyrosination/detyrosination cycle present in most eukaryotic cells. / ttl inhibits spontaneous tubulin polymerization	SIGNOR-176927
P12931	Q15691	1	phosphorylation	down-regulates activity	0.2	These data suggest that Src phosphorylates endogenous EB1 at Y247.	SIGNOR-278215
Q99626	P09848	1	transcriptional regulation	up-regulates quantity by expression	0.362	By electrophoretic mobility-shift assay it was shown that the factor Cdx-2 (a homoeodomain-protein related to caudal) binds to a TTTAC sequence in the CE-LPH1. Furthermore it was demonstrated that Cdx-2 is able to activate reporter gene transcription by binding to CE-LPH1.	SIGNOR-253964
Q14344	P30556	2	binding	up-regulates	0.522	These results indicate that ang ii increases endothelial arginase activity/expression through galfa12/13 g proteins coupled to at(1) receptors and subsequent activation of rhoa/rock/p38 mapk pathways leading to endothelial dysfunction.	SIGNOR-171760
P10828	Q15643	2	binding	up-regulates	0.314	Trip230 binds to rb independently of thyroid hormone while it forms a complex with tr in a thyroid hormone-dependent manner. Ectopic expression of the protein trip230 in cells, but not a mutant form that does not bind to tr, enhances specifically tr-dependent transcriptional activity.	SIGNOR-50421
Q9UBU7	Q13535	0	phosphorylation	down-regulates	0.657	Dbf4/cdc7 (dbf4-dependent kinase (ddk)) is activated at the onset of s-phase, and its kinase activity is required for dna replication initiation from each origin. We identified novel atm/atr phosphorylation sites on dbf4 and showed that atm/atr-mediated phosphorylation of dbf4 is critical for the intra-s-phase checkpoint to inhibit dna replication.	SIGNOR-177809
P29353	Q92835	2	binding	up-regulates	0.696	The results indicate that ship, shc, and grb2 form a ternary complex in stimulated b cells, with grb2 stabilizing the interaction between shc and ship. The interactions between shc, grb2, and ship are therefore analogous to the interactions between shc, grb2, and sos. Shc and grb2 may help to localize ship to the cell membrane, regulating ship's inhibitory function following bcr stimulation.	SIGNOR-66949
O94856	P16157	1	relocalization	up-regulates quantity	0.685	Neurofascin, L1, NrCAM, NgCAM, and neuroglian are membrane-spanning cell adhesion molecules with conserved cytoplasmic domains that are believed to play important roles in development of the nervous system. This report presents biochemical evidence that the cytoplasmic domains of these molecules associate directly with ankyrins, a family of spectrin-binding proteins located on the cytoplasmic surface of specialized plasma membrane domains.	SIGNOR-266718
P06858	Q6Q788	2	binding	up-regulates activity	0.718	Apo A5 binds to and enhances the activity of lipoprotein lipase (LPL) enzyme	SIGNOR-251845
P20333	Q13077	2	binding	up-regulates	0.72	Traf1 interacts with tnf-r2 indirectly through heterodimer formation with traf2.	SIGNOR-33133
P45973	P68400	0	phosphorylation	up-regulates	0.368	Hp1_ was multiply phosphorylated at n-terminal serine residues (s11-14) in human and mouse cells and that this phosphorylation enhanced hp1_'s affinity for h3k9me. Unphosphorylatable mutant hp1_ exhibited severe heterochromatin localization defects in vivo, and its prolonged expression led to increased chromosomal instability.	SIGNOR-171707
Q02763	P29353	2	binding	up-regulates activity	0.58	Our results identified a novel interaction between Tie2 with the adapter molecule ShcA and suggested that this interaction may play a role in the regulation of migration and three-dimensional organization of endothelial cells induced by angiopoietin-1. Furthermore, Tyr-1101 of Tie2 was identified as the primary binding site for the SH2 domain of ShcA.	SIGNOR-242573
P43378	P40763	1	dephosphorylation	down-regulates activity	0.432	Results are presented as mean \u00b1 SD from three independent experiments. (B) PTPMeg2 inhibits STAT3-mediated transcriptional activity in a dose dependent manner.\|These results indicate that PTPMeg2 inhibits STAT3 activation with certain specificity.\|In this study, we demonstrated that PTPMeg2 dephosphorylates STAT3 at the Tyr705 residue by a direct interaction.	SIGNOR-276976
Q9UM11	Q9UI95	2	binding	down-regulates activity	0.544	The APC is activated in mitosis and G1 by CDC20 and CDH1, and inhibited by the checkpoint protein MAD2, a specific inhibitor of CDC20. We show here that a MAD2 homolog MAD2B also inhibits APC. MAD2B directly inhibits activation of APC by CDC20 and CDH1	SIGNOR-264902
Q99835	P63215	2	binding	up-regulates	0.2	Consistent with its predicted topology, smo couples to a specific family of inhibitory g protein (gis) to regulate hh signaling.	SIGNOR-148598
Q04759	Q04759	2	phosphorylation	up-regulates activity	0.2	Critical role of novel Thr-219 autophosphorylation for the cellular function of PKCtheta in T lymphocytes.	SIGNOR-249298
P53667	Q9Y281	1	phosphorylation	down-regulates activity	0.703	Cofilin is known to be a potent regulator of actin filament dynamics, and its ability to bind and depolymerize actin is abolished by phosphorylation of serine residue at 3;. Here we show that lim-kinase 1 (limk-1), a serine/threonine kinase containing lim and pdz domains, phosphorylates cofilin at ser 3, both in vitro and in vivo	SIGNOR-58596
P31749	Q09472	1	phosphorylation	up-regulates	0.697	We find that suberoylanilide hydroxamic acid stimulates akt activity, which is required to phosphorylate p300 at ser(1834). Akt-mediated phosphorylation of p300 dramatically increases its acetyltransferase activity	SIGNOR-148983
Q9UBC7	O43603	2	binding	up-regulates	0.43	Galp is therefore an endogenous ligand that preferentially binds the galr2 receptor	SIGNOR-73143
P54577	Q2TAL8	0	transcriptional regulation	up-regulates quantity by expression	0.2	QRICH1 promotes the expression of translation-related genes. our combined ChIP-seq and RNA-seq analyses identified that QRICH1 and ATF4 were enriched at the promoters of these specific tRNA synthetases, and that ER stress positively regulated their transcription (Fig. 4I). Together, these findings suggest that QRICH1 and ATF4 modulate tRNA metabolic processes to promote secreted protein synthesis during ER stress.	SIGNOR-269412
P58401	Q8N2Q7	2	binding	up-regulates activity	0.829	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-264159
Q12860	Q9UHC6	0	relocalization	up-regulates activity	0.477	These results suggest that the targeting of contactin to different axonal domains may be determined, in part, via its association with Caspr.	SIGNOR-269074
P17252	P05114	1	phosphorylation	down-regulates	0.307	Protein kinases that phosphorylate hmg-14 17 at the major sites have been implicated from previous in vitro studies. Protein kinase c and a similar calcium phospholipid-dependent kinase have been reported to phosphorylate both proteins in vitro, where the phosphorylation of hmg-17 occurs predominantly at ser24 and to a lesser degree at ser28. Phosphorylation of hmg-14 at ser6 by camp- or cgmp-dependent kinases has also been reported. Thus, other kinases may contribute to phosphorylation at ser6 in response to oa. Ser88 and ser98 on hmg-14 are also phosphorylated by casein kinase ii in vitro. we conclude that the correlation we observe reflects a causal relationship, in which phosphorylation somehow facilitates the redistribution of hmg-14 and -17 toward non-nuclear pools.	SIGNOR-76286
Q13043	P26927	0	phosphorylation	up-regulates	0.524	We directly show that okadaic acid induces phosphorylation in the activation loop of mst, and, once phosphorylated, mst is rapidly translocated to the nucleus. when thr183 in mst1 was mutated to ala, no band could be detected by oa treatment,2 indicating that thr183 was the site of phosphorylation.	SIGNOR-114289
Q15208	Q9BXF6	1	phosphorylation	up-regulates activity	0.2	We identified 5 potential NDR1 substrates in the mouse brain and chose two for functional validation. We show that one NDR1 substrate is another kinase, AP-2 associated kinase-1 (AAK1) which regulates dendritic branching as a result of NDR1 phosphorylation. Another substrate is the Rab8 guanine nucleotide exchange factor (GEF) Rabin8 (a Sec2p homolog) which we find is involved in spine synapse formation.	SIGNOR-263035
P17612	Q14344	1	phosphorylation	down-regulates activity	0.366	PKA directly phosphorylates Galpha(13). Galpha(13)-T203A mutant (in COS-7 cells) could not be phosphorylated by PKA. PKA blocks Rho activation by phosphorylation of Galpha(13) Thr(203).	SIGNOR-249985
Q9H2X9	Q9BYP7	0	phosphorylation	down-regulates activity	0.46	We have shown that with-no-lysine kinase 3 (WNK3) possesses several properties that suggest it could be the Cl−/volume-sensitive regulatory kinase that, in association with protein phosphatases, reciprocally modifies the phosphorylation/dephosphorylation states of the SLC12 proteins and thus their activities\|WNK3 activates NKCC1/2 and NCC and inhibits the KCCs	SIGNOR-264628
P30874	P31629	0	transcriptional regulation	up-regulates quantity by expression	0.411	Activation of somatostatin receptor II expression by transcription factors MIBP1 and SEF-2 in the murine brain.	SIGNOR-261617

O60729

Q13309

1

dephosphorylation

down-regulates quantity by destabilization

0.357

The activity of SCF(Skp2) is regulated by the Cyclin-dependent kinase (CDK)2-mediated phosphorylation of Skp2 on Ser64 allows its expression in mid-G1 phase, even in the presence of active APC(Cdh1). Reciprocally, dephosphorylation of Skp2 by the mitotic phosphatase Cdc14B at the M --> G1 transition promotes its degradation by APC(Cdh1).

SIGNOR-248333

Q9UQ26

A6NJZ7

2

binding

down-regulates activity

0.265

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

SIGNOR-264367

Q9H992

P10636

1

ubiquitination

down-regulates activity

0.2

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

SIGNOR-278655

Q99708

P14618

0

phosphorylation

up-regulates activity

0.2

Here, we uncover an unexpected mechanism through which pyruvate kinase M2 (PKM2), the highly expressed PK isoform in cancer cells and a master regulator of cancer metabolic reprogramming, integrates with the DDR to directly promote DNA double-strand break (DSB) repair. In response to ionizing radiation and oxidative stress, ATM phosphorylates PKM2 at T328 resulting in its nuclear accumulation.

SIGNOR-277413

Q13547

O95471

1

transcriptional regulation

down-regulates quantity by repression

0.2

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

SIGNOR-254106

Q15256

Q16539

1

dephosphorylation

down-regulates

0.558

As shown, gst-ptp-sl dephosphorylated efficiently both erk2 and p38 wild typetogether, these results indicate that the defective association of the tyrosine phosphatase ptp-sl with erk2 d319n and p38 d316n mutations impairs the retention and inactivation in the cytosol of these map kinases by ptp-sl.

SIGNOR-111762

Q9H3K2

P99999

1

relocalization

down-regulates quantity

0.255

MICS1 was clearly coprecipitated with cytochrome c-3FLAG and the amount was DSP concentration-dependent (Figure 6A). Together with the finding that overexpression of exogenous MICS1 delayed the apoptotic release of cytochrome c in normal-serum level medium (Figure 4A), these results suggest that MICS1 helps to retain cytochrome c in the inner membrane, apart from the morphological changes.

SIGNOR-260294

O15360

Q13535

0

phosphorylation

up-regulates

0.598

The s1449a mutant failed to completely correct a variety of fa-associated phenotypes. The dna damage response is coordinated by phosphorylation events initiated by apical kinases atm (ataxia telangectasia mutated) and atr (atm and rad3-related), and atr is essential for proper fa pathway function. Serine 1449 is in a consensus atm/atr site

SIGNOR-182953

Q15185

P07900

2

binding

up-regulates activity

0.916

The mutant Hsp90 proteins tested are defective in the binding and ATP hydrolysis-dependent cycling of the co-chaperone p23, which is thought to regulate the binding and release of substrate polypeptide from Hsp90.

SIGNOR-262831

P08151

Q15915

0

relocalization

up-regulates

0.377

Co-expression of zic1 resulted in gli1 and gli3 proteins being translocated to the nucleus in varying levels

SIGNOR-105491

P68400

O15259

1

phosphorylation

up-regulates

0.2

Casein kinase 2 (ck2)-mediated phosphorylation of three critical serine residues within a cluster of acidic amino acids in nephrocystin mediates pacs-1 binding, and is essential for colocalization of nephrocystin with pacs-1 at the base of cilia. Inhibition of ck2 activity abrogates this interaction and results in the loss of correct nephrocystin targeting.

SIGNOR-142343

Q15465

Q9Y6C5

2

binding

down-regulates activity

0.803

Biochemical analysis of ptch and ptch2 shows that they both bind to all hedgehog family members with similar affinity and that they can form a complex with smo.Current models suggest that binding of Shh to PTCH prevents the normal inhibition of the seven-transmembrane-protein Smoothened (SMO) by PTCH.

SIGNOR-217776

Q15797

P36894

0

phosphorylation

up-regulates activity

0.732

Two types of bmp-induced signaling pathways are known, the smad and p38 mapk pathways. In the former case, bmpr1 phosphorylates smad-1,-5,-8, which forms a complex with smad4 that translocates into the nucleus and regulates gene expression.

SIGNOR-255263

P12931

Q16825

0

dephosphorylation

up-regulates

0.643

Ptpd1 activates src tyrosine kinase and increases the magnitude and duration of epidermal growth factor (egf) signaling.

SIGNOR-124774

P63096

P35408

2

binding

up-regulates activity

0.312

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-257032

P37802

O94921

0

phosphorylation

down-regulates activity

0.315

This newly identified oncogene–tumor suppressor cascade, where oncogenic PFTK1 inactivates a tumor suppressor gene TAGLN2 via phosphorylation|. Our data therefore underline much importance for S83 and S163 residues on TAGLN2 in its actin-binding capacity.

SIGNOR-265103

Q99677

P08754

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-257170

O14974

Q9H093

0

phosphorylation

down-regulates activity

0.466

NUAK2 phosphorylates and inhibits MYPT1, the regulatory subunit of MLC phosphatase, stabilizing actin filaments and mediating contraction of smooth muscle cells ( xref ).

SIGNOR-279081

Q7Z2K8

P51608

0

post transcriptional regulation

up-regulates quantity by expression

0.298

MeCP2 binds to the promoter region of six target genes. ChIP with anti-MeCP2 antibody shows that MeCP2 binds to the promoter regions of activated targets Sst, Oprk1, Gamt, and Gprin1, and repressed targets Mef2c and A2bp1.

SIGNOR-264679

P68400

P18887

1

phosphorylation

up-regulates

0.395

Xrcc1 phosphorylation by ck2 is required for its stability and efficient dna repair

SIGNOR-165419

Q92993

P62805

1

acetylation

down-regulates activity

0.2

Thus, the TIP60 HAT complex is recruited to MYC-target genes and, probably with other other HATs, contributes to histone acetylation in response to mitogenic signals.

SIGNOR-262061

Q13131

Q8N122

1

phosphorylation

down-regulates activity

0.687

Ampk in turn inactivates mtorc1 directly by phosphorylating raptor and indirectly by phosphorylating tsc2.

SIGNOR-173035

P06241

P18433

0

dephosphorylation

up-regulates

0.658

Ptpalpha is a more widely expressed transmembrane ptp that has been shown to regulate the src family kinases, src and fyn, and is also present in t cells.

SIGNOR-154796

P36894

O95476

2

binding

up-regulates

0.291

We show that dullard promotes the ubiquitin-mediated proteosomal degradation of bmp receptors (bmprs). Dullard preferentially complexes with the bmp type ii receptor (bmprii) and partially colocalizes with the caveolin-1-positive compartment, suggesting that dullard promotes bmpr degradation via the lipid raft-caveolar pathway

SIGNOR-150998

Q8NA31

O94901

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-263299

P51813

Q96T51

1

phosphorylation

up-regulates activity

0.634

Etk interacts with RUFY1 through its SH3 and SH2 domains. RUFY1 is tyrosine-phosphorylated and appears to be a substrate of Etk. Phosphorylation of the two tyrosine residues, Tyr-281 and Tyr-292, located in the linker region of the two coiled-coil domains by Etk seems to be critical for RUFY1 targeting to the endosomes.

SIGNOR-262679

P28482

Q13362

2

phosphorylation

down-regulates

0.513

Iex-1 binds to b56 subunits and perk independently, enhances b56 phosphorylation by erk at a conserved ser/pro site in this complex and triggers dissociation from the catalytic subunit.

SIGNOR-144313

Q92918

P46109

2

binding

up-regulates

0.587

We found that hpk1 interacted with crk and crkl adaptor proteins in vitro and in vivo and that the proline-rich motifs within hpk1 were involved in the differential interaction of hpk1 with the crk proteins and grb2. Crk and crkl not only activated hpk1 but also synergized with hpk1 in the activation of jnk.

SIGNOR-63991

O15111

Q9Y243

0

phosphorylation

up-regulates

0.414

Although there are likely to be multiple levels of crosstalk between the pi3k-akt and nf-kb pathways, one mechanism has been attributed to direct phosphorylation of the amino acid residue t23 on ikb kinase alfa (ikkalfa) by akt, thereby leading to activation of this kinase upstream of nf-kb akt mediates ikkalpha phosphorylation at threonine 23 akt transiently associates in vivo with ikk and induces ikk activation. Akt mediates ikkalfa phosphorylation at threonine 23.Akt phosphorylates ikkalpha on t23, and this phosphorylation event is a prerequisite for the phosphorylation of p65 at s534 by ikkalpha and beta

SIGNOR-187062

Q01082

Q12955

2

binding

up-regulates activity

0.644

Ankyrin-G is a molecular partner of E-cadherin in epithelial cells and early embryos. Ankyrin-G also recruits beta-2-spectrin to E-cadherin-beta-catenin complexes, thus providing a direct connection between E-cadherin and the spectrin/actin skeleton.

SIGNOR-266711

P48382

P01903

1

transcriptional regulation

up-regulates quantity by expression

0.503

In this report, we correlate the loss of IFN-γ induction of MHC class II genes with the identification of a molecular defect in an essential regulator, namely RFX5. | We have further confirmed this finding by showing that new RFX5 leucine mutants created in vitro are incapable of transactivating a class II promoter, suggesting the identification of residues essential for RFX activity.

SIGNOR-266228

P40763

Q5VWQ8

2

binding

down-regulates activity

0.346

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

SIGNOR-254761

P51955

Q07955

1

phosphorylation

down-regulates activity

0.385

First, NEK2 interacts with and phosphorylates SRSF1.

SIGNOR-279344

P07949

P78527

1

phosphorylation

up-regulates activity

0.27

Phosphorylation of DNA-PKcs at s2056 is elevated in RET expressing cells and can be reduced by RET inhibition.

SIGNOR-279275

P45983

Q07817

1

phosphorylation

down-regulates

0.775

By site-directed mutagenesis studies, we have identified that serine 62 is the necessary site for taxol- or 2-me-induced bcl-xl phosphorylation in prostate cancer cells. Further studies with the inhibitor of jun kinase (jnk) and phosphorylation mutant of bcl-xl reveal the augmentative role of jnk-mediated bcl-xl phosphorylation in apoptosis of prostate cancer cells. In summary, our studies suggest that the phosphorylation of bcl-xl by stress response kinase signaling might oppose the anti-apoptotic function of bcl-xl to permit prostate cancer cells to die by apoptosis

SIGNOR-99219

O15550

Q05516

1

transcriptional regulation

up-regulates quantity by expression

0.311

UTX catalytic activity has been reported to upregulate expression of the master transcription factor PLZF and to modulate superenhancer accessibility in invariant natural killer T cells.

SIGNOR-260038

P53350

O43524

1

phosphorylation

down-regulates activity

0.491

Furthermore, PLK1 can directly phosphorylate FOXO3 in an in vitro kinase assay.|PLK1 induces translocation of FOXO3 from the nucleus to the cytoplasm and suppresses FOXO3 activity, measured by the decrease in the pro-apoptotic Bim protein levels and in the cell cycle inhibitor protein p27.

SIGNOR-279095

P52333

Q9HBE5

2

binding

up-regulates

0.558

Retroviral-mediated transduction of wild-type gamma c into xscid jt cells restored function to the il-21r, as shown by il-21-induced tyrosine phosphorylation of jak1 and jak3, and downstream activation of stat5

SIGNOR-90269

P53396

P17612

0

phosphorylation

up-regulates activity

0.309

Phosphorylation of Recombinant Human ATP:Citrate Lyase by cAMP-Dependent Protein Kinase Abolishes Homotropic Allosteric Regulation of the Enzyme by Citrate and Increases the Enzyme Activity. Ser 454, which is phosphorylated by the catalytic subunit of cAMP-dependent protein kinase (PKA)

SIGNOR-250328

P00533

P15941

1

phosphorylation

up-regulates activity

0.577

We also show that the activated egf-r phosphorylates the muc1 cytoplasmic tail on tyrosine at a yekv motif that functions as a binding site for the c-src sh2 domain. The results demonstrate that egf-r-mediated phosphorylation of muc1 induces binding of muc1 to c-src in cells

SIGNOR-109538

Q14493

Q6NXT2

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-265420

Q7Z434

Q14653

2

binding

up-regulates activity

0.8

Phosphorylated MAVS and STING then bind to a positively charged surface of interferon regulatory factor 3 (IRF3) and thereby recruit IRF3 for its phosphorylation and activation by TBK1.

SIGNOR-260143

P68400

O95863

1

phosphorylation

up-regulates quantity by stabilization

0.348

Serines 11 and 92 participate in the control of snail1 stability and positively regulate snail1 repressive function and its interaction with msin3a corepressor. Furthermore, serines 11 and 92 are required for snail1-mediated emt and cell viability, respectively. Pka and ck2 have been characterized as the main kinases responsible for in vitro snail1 phosphorylation at serine 11 and 92, respectively.

SIGNOR-161771

P53805

P28482

0

phosphorylation

up-regulates activity

0.27

Consensus phosphorylation sites for p42/44 MAPK and GSK-3 are present in the SP repeat of MCIP1 at serine 112 and serine 108, respectively |Several endogenous proteins are capable of inhibiting the catalytic activity of calcineurin. Modulatory calcineurin interacting protein 1 (MCIP1) is unique among these proteins on the basis of its pattern of expression and its function in a negative feedback loop to regulate calcineurin activity. Here we show that MCIP1 can be phosphorylated by MAPK and glycogen synthase kinase-3 and that phosphorylated MCIP1 is a substrate for calcineurin.

SIGNOR-249198

Q969V1

Q03113

2

binding

up-regulates activity

0.25

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

SIGNOR-257439

P55011

Q9BYP7

0

phosphorylation

up-regulates activity

0.525

We have shown that with-no-lysine kinase 3 (WNK3) possesses several properties that suggest it could be the Cl−/volume-sensitive regulatory kinase that, in association with protein phosphatases, reciprocally modifies the phosphorylation/dephosphorylation states of the SLC12 proteins and thus their activities|WNK3 activates NKCC1/2 and NCC and inhibits the KCCs

SIGNOR-264625

P10523

Q93034

2

binding

up-regulates quantity by stabilization

0.412

Here we report that NEDD4-1, a HECT domain-containing E3 ubiquitin ligase, binds via its HECT domain directly with SAG's C-terminal RING domain and ubiquitylates SAG for proteasome-mediated. We also found that SAG bridges NEDD4-1 via its C-terminus and CUL-5 via its N-terminus to form a NEDD4-1/SAG/CUL-5 tri-complex. Biologically, NEDD4-1 overexpression sensitizes cancer cells to etoposide-induced apoptosis by reducing SAG levels through targeted degradation. Thus, SAG is added to a growing list of NEDD4-1 substrates and mediates its biological function. degradation.

SIGNOR-272844

P19525

O75569

1

phosphorylation

up-regulates activity

0.796

In stressed cells, this activation occurs when PACT, a PKR-binding protein, is phosphorylated and activates PKR.

SIGNOR-280003

P20393

P35398

2

binding

down-regulates activity

0.461

Direct Regulation of the NPAS2 Promoter by RORα and REV-ERBα. it appears in the context of the NPAS2 promoter RORα functions as a transcriptional activator, but REV-ERBα may only function as an inhibitor of RORα activity by blocking binding.

SIGNOR-267979

O43524

Q14680

0

phosphorylation

down-regulates quantity

0.362

Further analysis indicated that FOXO1 and FOXO3, two known transcriptional regulators of p21, were phosphorylated by MELK and thus be involved in the induction of p21 after MELK inhibition.|Our findings revealed that siRNA mediated MELK knockdown increased protein levels of FOXO1 and FOXO3, which might increase p21 transcriptional level in a p53 independent manner.

SIGNOR-279375

P23470

P10721

1

dephosphorylation

down-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-254710

P37173

O00459

2

binding

up-regulates

0.433

These studies revealed that PI 3-kinase is associated in vivo with both TGF-_ receptor subtypes and that TGF-_1 stimulation enhances PI 3-kinase activity associated with type I TGF-_ receptor in hASM cells.

SIGNOR-227528

P16473

Q96T91

2

binding

up-regulates

0.546

Recombinant a2/b5 heterodimeric glycoproteins, purified using cation exchange and size fractionation chromatography, activated human tsh receptors, but not lh and fsh receptors, and showed high affinity to tsh receptors in a radioligand receptor assay

SIGNOR-88614

P06493

Q13286

1

phosphorylation

down-regulates activity

0.257

(D) Phosphorylation of Cln3 by Cdk1 is independent of Ssa1 T36.|Thereby, both Cdk1 and Pho85can promote Cln3 degradation, though under distinct circumstances.

SIGNOR-279013

O00220

Q13158

2

binding

up-regulates

0.831

Fadd binds to ligated trailr1 or trail-r2

SIGNOR-97869

Q01668

P17612

0

phosphorylation

up-regulates activity

0.396

We recently demonstrated that PKA activation led to increased alpha(1D) Ca(2+) channel activity in tsA201 cells by phosphorylation of the channel protein. Western blotting showed that the N terminus and C terminus were phosphorylated. Serines 1743 and 1816, two PKA consensus sites, were phosphorylated by PKA and identified by mass spectrometry.

SIGNOR-263109

P46527

P06493

2

binding

down-regulates

0.655

P21 and p27 are key inhibitors of both cdk1 and cdk2.

SIGNOR-128445

Q15561

P46937

2

binding

up-regulates activity

0.927

The multifunctional cytokine TGF-β has been identified as a potent inducer of CTGF expression, activating CTGF transcription through the canonical Smad signaling pathway. It is worth noting that TGF-β synergizes with Hippo–Yes-associated protein (YAP) signaling, a key regulator of tumorigenesis, to induce the expression of CTGF by the formation of a YAP-TEAD4-Smad3-p300 complex on the CTGF promoter

SIGNOR-277685

P46060

P68400

0

phosphorylation

up-regulates

0.31

Phosphorylation of rangap1 stabilizes its interaction with ran and ranbp1. Serine-358 (358s) was identified as the major phosphorylation site. Experiments using purified recombinant kinase and specific inhibitors such as drb and apigenin strongly suggest that casein kinase ii (ck2) is the responsible kinase

SIGNOR-143948

Q9Y463

P13807

1

phosphorylation

down-regulates activity

0.258

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-260633

P49841

Q96R06

1

phosphorylation

up-regulates

0.271

Astrin acts as a substrate for gsk3beta and is phosphorylated at thr-111, thr-937 ((s/t)p motif) and ser-974/thr-978 ((s/t)xxx(s/t)-p motif;p is a phosphorylatable residue). Inhibition of gsk3beta impairs spindle and kinetochore accumulation of astrin and spindle formation at mitosis, suggesting that astrin association with the spindle microtubule and kinetochore may be dependent on phosphorylation by gsk3beta

SIGNOR-159578

P32245

P01189

2

binding

up-regulates activity

0.778

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

SIGNOR-268710

Q16611

Q9BXH1

2

binding

up-regulates

0.382

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

SIGNOR-196929

P48506

Q16236

0

transcriptional regulation

up-regulates quantity by expression

0.47

In both models, the inducer-modified and Nrf2-bound Keap1 is inactivated and, consequently, newly synthesized Nrf2 proteins bypass Keap1 and translocate into the nucleus, bind to the ARE and drive the expression of Nrf2 target genes such as NAD(P)H quinone oxidoreductase 1 (NQO1), heme oxygenase 1 (HMOX1), glutamate-cysteine ligase (GCL) and glutathione S transferases (GSTs).

SIGNOR-256277

Q8TDQ0

Q08881

0

phosphorylation

up-regulates activity

0.31

When we tested the effect of ITK on the Y265 mutant, we found a pronounced reduction of ITK-mediated tyrosine phosphorylation, suggesting that Y265 is specifically phosphorylated by ITK (Fig. 3B). Our results demonstrate that specific phosphorylation of Y265 of Tim-3 occurs in the presence of galectin-9, probably through a receptor-ligand interaction. Phosphorylation of Y265, which is situated in a highly conserved SH2 binding domain, could result in the recruitment of SH2 containing adaptor proteins and trigger downstream signalling events regulating the fate of Tim-3 expressing T-cells.

SIGNOR-273644

P13796

P17612

0

phosphorylation

up-regulates

0.327

Phosphorylation on ser5 increases the f-actin-binding activity of l-plastin and promotes its targeting to sites of actin assembly in cells. L-plastin phosphorylation require protein kinase a.

SIGNOR-146287

P81133

P27540

2

binding

up-regulates activity

0.531

We demonstrate that both SIM1 and SIM2 can heterodimerize via their helix-loop-helix·PAS regions with ARNT, but not with AHR, and that they do not form homodimers. Furthermore, SIM1 may have a dual role, both negatively affecting AHR·ARNT binding to the XRE and also acting in concert with ARNT as a novel DNA-binding heterodimer.

SIGNOR-240759

P34995

O95837

2

binding

up-regulates activity

0.435

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

SIGNOR-257194

Q14161

Q05209

0

dephosphorylation

down-regulates

0.344

Conversely, a gfp-pkl phosphorylation mutant, y286/392/592f (gfp-pkl triple yf) (brown et al., 2005), was not phosphorylated during adhesion and the addition of ptp-pest had no effect, suggesting one or more of these tyrosine residues are dephosphorylated by ptppest. Taken together, these data strongly suggest pkl as a direct substrate for ptp-pest.

SIGNOR-142719

Q9Y253

Q13535

0

phosphorylation

up-regulates

0.415

Atr-mediated phosphorylation of dna polymerase _ is needed for efficient recovery from uv damage. We show that, after uv irradiation, pol_ becomes phosphorylated at ser601 by the ataxia-telangiectasia mutated and rad3-related (atr) kinase. Atr-dependent phosphorylation of pol_ is necessary to restore normal survival and postreplication repair

SIGNOR-171290

Q16778

Q14493

0

translation regulation

up-regulates quantity by expression

0.2

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

SIGNOR-265386

Q9UNE7

O60260

2

binding

up-regulates activity

0.2

In this study, we found that CHIP promotes Parkin-mediated Pael-R ubiquitination and subsequent degradation. In vitro ubiquitination assays suggested that only a combination of both Parkin and its cofactor CHIP function as a ubiquitin ligase, which is able to sufficiently ubiquitinate Pael-R in vivo (Figure 6).

SIGNOR-272888

P68366

Q8NG68

0

tyrosination

down-regulates

0.286

Tubulin tyrosine ligase (ttl) adds a c-terminal tyr to __tubulin as part of a tyrosination/detyrosination cycle present in most eukaryotic cells. / ttl inhibits spontaneous tubulin polymerization

SIGNOR-176927

P12931

Q15691

1

phosphorylation

down-regulates activity

0.2

These data suggest that Src phosphorylates endogenous EB1 at Y247.

SIGNOR-278215

Q99626

P09848

1

transcriptional regulation

up-regulates quantity by expression

0.362

By electrophoretic mobility-shift assay it was shown that the factor Cdx-2 (a homoeodomain-protein related to caudal) binds to a TTTAC sequence in the CE-LPH1. Furthermore it was demonstrated that Cdx-2 is able to activate reporter gene transcription by binding to CE-LPH1.

SIGNOR-253964

Q14344

P30556

2

binding

up-regulates

0.522

These results indicate that ang ii increases endothelial arginase activity/expression through galfa12/13 g proteins coupled to at(1) receptors and subsequent activation of rhoa/rock/p38 mapk pathways leading to endothelial dysfunction.

SIGNOR-171760

P10828

Q15643

2

binding

up-regulates

0.314

Trip230 binds to rb independently of thyroid hormone while it forms a complex with tr in a thyroid hormone-dependent manner. Ectopic expression of the protein trip230 in cells, but not a mutant form that does not bind to tr, enhances specifically tr-dependent transcriptional activity.

SIGNOR-50421

Q9UBU7

Q13535

0

phosphorylation

down-regulates

0.657

Dbf4/cdc7 (dbf4-dependent kinase (ddk)) is activated at the onset of s-phase, and its kinase activity is required for dna replication initiation from each origin. We identified novel atm/atr phosphorylation sites on dbf4 and showed that atm/atr-mediated phosphorylation of dbf4 is critical for the intra-s-phase checkpoint to inhibit dna replication.

SIGNOR-177809

P29353

Q92835

2

binding

up-regulates

0.696

The results indicate that ship, shc, and grb2 form a ternary complex in stimulated b cells, with grb2 stabilizing the interaction between shc and ship. The interactions between shc, grb2, and ship are therefore analogous to the interactions between shc, grb2, and sos. Shc and grb2 may help to localize ship to the cell membrane, regulating ship's inhibitory function following bcr stimulation.

SIGNOR-66949

O94856

P16157

1

relocalization

up-regulates quantity

0.685

Neurofascin, L1, NrCAM, NgCAM, and neuroglian are membrane-spanning cell adhesion molecules with conserved cytoplasmic domains that are believed to play important roles in development of the nervous system. This report presents biochemical evidence that the cytoplasmic domains of these molecules associate directly with ankyrins, a family of spectrin-binding proteins located on the cytoplasmic surface of specialized plasma membrane domains.

SIGNOR-266718

P06858

Q6Q788

2

binding

up-regulates activity

0.718

Apo A5 binds to and enhances the activity of lipoprotein lipase (LPL) enzyme

SIGNOR-251845

P20333

Q13077

2

binding

up-regulates

0.72

Traf1 interacts with tnf-r2 indirectly through heterodimer formation with traf2.

SIGNOR-33133

P45973

P68400

0

phosphorylation

up-regulates

0.368

Hp1_ was multiply phosphorylated at n-terminal serine residues (s11-14) in human and mouse cells and that this phosphorylation enhanced hp1_'s affinity for h3k9me. Unphosphorylatable mutant hp1_ exhibited severe heterochromatin localization defects in vivo, and its prolonged expression led to increased chromosomal instability.

SIGNOR-171707

Q02763

P29353

2

binding

up-regulates activity

0.58

Our results identified a novel interaction between Tie2 with the adapter molecule ShcA and suggested that this interaction may play a role in the regulation of migration and three-dimensional organization of endothelial cells induced by angiopoietin-1. Furthermore, Tyr-1101 of Tie2 was identified as the primary binding site for the SH2 domain of ShcA.

SIGNOR-242573

P43378

P40763

1

dephosphorylation

down-regulates activity

0.432

Results are presented as mean \u00b1 SD from three independent experiments. (B) PTPMeg2 inhibits STAT3-mediated transcriptional activity in a dose dependent manner.|These results indicate that PTPMeg2 inhibits STAT3 activation with certain specificity.|In this study, we demonstrated that PTPMeg2 dephosphorylates STAT3 at the Tyr705 residue by a direct interaction.

SIGNOR-276976

Q9UM11

Q9UI95

2

binding

down-regulates activity

0.544

The APC is activated in mitosis and G1 by CDC20 and CDH1, and inhibited by the checkpoint protein MAD2, a specific inhibitor of CDC20. We show here that a MAD2 homolog MAD2B also inhibits APC. MAD2B directly inhibits activation of APC by CDC20 and CDH1

SIGNOR-264902

Q99835

P63215

2

binding

up-regulates

0.2

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

SIGNOR-148598

Q04759

2

phosphorylation

up-regulates activity

0.2

Critical role of novel Thr-219 autophosphorylation for the cellular function of PKCtheta in T lymphocytes.

SIGNOR-249298

P53667

Q9Y281

1

phosphorylation

down-regulates activity

0.703

Cofilin is known to be a potent regulator of actin filament dynamics, and its ability to bind and depolymerize actin is abolished by phosphorylation of serine residue at 3;. Here we show that lim-kinase 1 (limk-1), a serine/threonine kinase containing lim and pdz domains, phosphorylates cofilin at ser 3, both in vitro and in vivo

SIGNOR-58596

P31749

Q09472

1

phosphorylation

up-regulates

0.697

We find that suberoylanilide hydroxamic acid stimulates akt activity, which is required to phosphorylate p300 at ser(1834). Akt-mediated phosphorylation of p300 dramatically increases its acetyltransferase activity

SIGNOR-148983

Q9UBC7

O43603

2

binding

up-regulates

0.43

Galp is therefore an endogenous ligand that preferentially binds the galr2 receptor

SIGNOR-73143

P54577

Q2TAL8

0

transcriptional regulation

up-regulates quantity by expression

0.2

QRICH1 promotes the expression of translation-related genes. our combined ChIP-seq and RNA-seq analyses identified that QRICH1 and ATF4 were enriched at the promoters of these specific tRNA synthetases, and that ER stress positively regulated their transcription (Fig. 4I). Together, these findings suggest that QRICH1 and ATF4 modulate tRNA metabolic processes to promote secreted protein synthesis during ER stress.

SIGNOR-269412

P58401

Q8N2Q7

2

binding

up-regulates activity

0.829

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-264159

Q12860

Q9UHC6

0

relocalization

up-regulates activity

0.477

These results suggest that the targeting of contactin to different axonal domains may be determined, in part, via its association with Caspr.

SIGNOR-269074

P17252

P05114

1

phosphorylation

down-regulates

0.307

Protein kinases that phosphorylate hmg-14 17 at the major sites have been implicated from previous in vitro studies. Protein kinase c and a similar calcium phospholipid-dependent kinase have been reported to phosphorylate both proteins in vitro, where the phosphorylation of hmg-17 occurs predominantly at ser24 and to a lesser degree at ser28. Phosphorylation of hmg-14 at ser6 by camp- or cgmp-dependent kinases has also been reported. Thus, other kinases may contribute to phosphorylation at ser6 in response to oa. Ser88 and ser98 on hmg-14 are also phosphorylated by casein kinase ii in vitro. we conclude that the correlation we observe reflects a causal relationship, in which phosphorylation somehow facilitates the redistribution of hmg-14 and -17 toward non-nuclear pools.

SIGNOR-76286

Q13043

P26927

0

phosphorylation

up-regulates

0.524

We directly show that okadaic acid induces phosphorylation in the activation loop of mst, and, once phosphorylated, mst is rapidly translocated to the nucleus. when thr183 in mst1 was mutated to ala, no band could be detected by oa treatment,2 indicating that thr183 was the site of phosphorylation.

SIGNOR-114289

Q15208

Q9BXF6

1

phosphorylation

up-regulates activity

0.2

We identified 5 potential NDR1 substrates in the mouse brain and chose two for functional validation. We show that one NDR1 substrate is another kinase, AP-2 associated kinase-1 (AAK1) which regulates dendritic branching as a result of NDR1 phosphorylation. Another substrate is the Rab8 guanine nucleotide exchange factor (GEF) Rabin8 (a Sec2p homolog) which we find is involved in spine synapse formation.

SIGNOR-263035

P17612

Q14344

1

phosphorylation

down-regulates activity

0.366

PKA directly phosphorylates Galpha(13). Galpha(13)-T203A mutant (in COS-7 cells) could not be phosphorylated by PKA. PKA blocks Rho activation by phosphorylation of Galpha(13) Thr(203).

SIGNOR-249985

Q9H2X9

Q9BYP7

0

phosphorylation

down-regulates activity

0.46

We have shown that with-no-lysine kinase 3 (WNK3) possesses several properties that suggest it could be the Cl−/volume-sensitive regulatory kinase that, in association with protein phosphatases, reciprocally modifies the phosphorylation/dephosphorylation states of the SLC12 proteins and thus their activities|WNK3 activates NKCC1/2 and NCC and inhibits the KCCs

SIGNOR-264628

P30874

P31629

0

transcriptional regulation

up-regulates quantity by expression

0.411

Activation of somatostatin receptor II expression by transcription factors MIBP1 and SEF-2 in the murine brain.

SIGNOR-261617