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
Q9Y3A6	P49755	2	binding	up-regulates activity	0.568	P28 forms hetero-oligomeric complexes with p23. p23 is a major determinant for efficient targeting of p28 to the ERGIC	SIGNOR-261298
P17936	P68400	0	phosphorylation	up-regulates quantity by stabilization	0.338	The importance of Ser111 and Ser113 as targets for CK2 has also been shown in our laboratory, as mutation of either residue to alanine caused a major decrease in IGFBP-3 phosphorylation by this enzyme in vitro \| These results indicate that IGFBP-3 interaction with acid-labile subunit and with the cell surface, both of which involve basic carboxyl-terminal residues, may be modulated by phosphorylation. Relative resistance to proteolysis and poor binding to cells suggest that CK2-phospho-IGFBP-3 may be a significant inhibitor of IGF activity in the extracellular environment.	SIGNOR-250903
P16104	P78527	0	phosphorylation	up-regulates	0.2	Dna-dependentprotein_ kinase_ (dna-pk) that phosphorylate h2ax at dsbs	SIGNOR-192443
P08151	P17612	0	phosphorylation	down-regulates	0.551	We report that activation of PKA retains Gli1 in the cytoplasm. Conversely, inhibition of PKA activity promotes nuclear accumulation of Gli1.We provide direct evidence to support that the cAMP/PKA signaling axis regulates Gli1 protein localization primarily through a site at Thr374. .These data suggest that Thr374 is an important PKA site responsible for PKA phosphorylation and for the transcriptional activity of Gli1.	SIGNOR-253539
O60825	P54646	0	phosphorylation	up-regulates activity	0.443	AMPK phosphorylates and activates heart PFK-2 in vitro and in intact cells. activation of PFK-2 was due to the phosphorylation of Ser466	SIGNOR-250323
P98172	P54762	2	binding	up-regulates	0.827	We show here that despite its lack of kinase activity, ephb6 undergoes inducible tyrosine phosphorylation upon stimulation with the eph-b receptor subfamily ligand ephrin-b1. Overexpression of a catalytically active member of the eph-b subfamily, ephb1, resulted in increased ephb6 phosphorylation. Ephb1-induced ephb6 phosphorylation was ligand-dependent and required the functional catalytic activity of ephb1.	SIGNOR-111851
Q15139	P35670	1	phosphorylation	up-regulates activity	0.296	ATP7B trafficking was markedly reduced by the Ser-478/481/1121/1453 to Ala mutation. We conclude that PKD plays a key role in copper-dependent serine phosphorylation, permitting high levels of ATP7B protein expression and trafficking.	SIGNOR-272295
P46527	Q14012	0	phosphorylation	up-regulates activity	0.305	We also demonstrate that i) CaMKI phosphorylates p27 at Thr157and Thr198 in human cells and at Thr170and Thr197in mouse cells to modulate its subcellular localization;\|Collectively, these results suggest that CaMKI is involved in mediating G1 progression by promoting cyclin D1/cdk4 complex formation through site-specific p27 phosphorylation in human lung epithelia.	SIGNOR-261194
P00519	P29474	1	phosphorylation	up-regulates activity	0.2	Two kinases, i.e. abelson-tyrosine protein kinase (ABL)1 and Src were identified as eNOS Tyr81 kinases as their inhibition and down-regulation significantly reduced the basal and Yoda1-induced tyrosine phosphorylation and activity of eNOS.	SIGNOR-277519
P01178-PRO_0000020495	Q92824	0	cleavage	up-regulates quantity	0.2	Oxytocin-extended form is further cleaved by enzymatic activity to yield the nine-amino-acid active peptide, OT. The proteolysis may involve several pro-hormone convertases, convertase 2 (PC2) (20p11-1-11.2) and convertase 5 (PC5) (9q21.3) (Gabreels et al 1998). Both enzymes are found in OT neurosecretory vesicles and are a part of a family of subtilisen/kexinlike convertases (Seidah et al 1994). It is a product of the OT gene located at human gene locus 20p13 (Rao et al 1992). The processing cascade results in the production of neurophysin I and OT extended form (OT-X), which is OT with a C-terminal, three-amino-acid extension.	SIGNOR-270334
Q9P035	P49327	1	chemical activation	up-regulates activity	0.2	Very long-chain fatty acids are produced through a four-step cycle. However, the 3-hydroxyacyl-CoA dehydratase catalyzing the third step in mammals has remained unidentified. Mammals have four candidates, HACD1-4, based on sequence similarities to the recently identified yeast Phs1, although HACD3 and HACD4 share relatively weak similarity. We demonstrate that all four of these human proteins are indeed 3-hydroxyacyl-CoA dehydratases,	SIGNOR-267762
Q00535	P14416	1	phosphorylation	down-regulates activity	0.383	These results indicate that Cdk5-mediated phosphorylation of S321 inhibits DRD2 function, providing a novel regulatory mechanism for dopamine signaling.	SIGNOR-259401
P41970	O15550	0	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-260037
Q02750	Q9Y2G1	1	phosphorylation	down-regulates activity	0.258	Mek1 phosphorylation of Ndt80 therefore provides an elegant way for cells to know when it is safe to enter the first meiotic division.\|These observations suggest that phosphorylation of the DBD by Mek1 prevents Ndt80 from binding to MSEs and explains how Mek1 phosphorylation can inhibit Ndt80 activity.	SIGNOR-279416
Q13535	Q14566	1	phosphorylation	up-regulates	0.562	Together these data strongly support the conclusion that mec1 directly targets the s/tq sites in mcm4 and mcm6, although it is formally possible that mec1 and mrc1 activate a different s/tq-directed kinase to target mcm4 and mcm6.	SIGNOR-169450
P34947	P50502	1	phosphorylation	up-regulates activity	0.268	An in vitro screen for novel GRK substrates revealed Hsp70 interacting protein (Hip) as a substrate. GRK5, but not GRK2, bound to and stoichiometrically phosphorylated Hip in vitro. The primary binding domain of GRK5 was mapped to residues 303-319 on Hip, while the major site of phosphorylation was identified to be Ser-346. GRK5 also bound to and phosphorylated Hip on Ser-346 in cells.we found that the phosphorylation of Ser-346 was required for proper agonist-induced internalization of the chemokine receptor CXCR4.	SIGNOR-262877
Q13422	P62136	0	dephosphorylation	up-regulates	0.279	Ikarosis dephosphorylated by protein phosphatase 1 (pp1) via interaction at a consensus pp1-binding motif/ hyperphosphorylation of ikaros promotes its degradation by the ubiquitin/proteasome pathway	SIGNOR-174859
P28324	P24941	0	phosphorylation	up-regulates activity	0.363	Phosphorylation of ELK4 at Thr194 and Ser387 by CDK2 is required for EGF-induced cell transformation.	SIGNOR-278210
Q13285	P10275	2	binding	up-regulates	0.409	Ar suppresses transcription of the lhbeta subunit by interacting with steroidogenic factor-1.	SIGNOR-109996
P78317	P25208	2	binding	up-regulates activity	0.2	Coactivator RNF4 is involved in the GCH gene expression. Through serial deletion and mutagenesis studies of the GCH promoter, we defined the RNF4-responsive element on GCH proximal promoter as a CCAAT box. RNF4 did not possess specific DNA binding activity toward this CCAAT box, which suggests that RNF4 may be a coactivator of the CCAAT boxbinding protein nuclear factor Y (NF-Y). RNF4 is a coactivator for nuclear factor Y on GTP cyclohydrolase I proximal promoter.	SIGNOR-252230
Q8IV08	P05067	2	binding	up-regulates quantity	0.373	Furthermore, PLD3 can be co-immunoprecipitated with APP in cultured cells (Extended Data Figure 4). Together, these studies demonstrate that PLD3 plays a role in APP processing. Over-expression of PLD3 leads to a significant decrease in intracellular APP and extracellular Aβ42 and Aβ40, while knock-down of PLD3 leads to a significant increase in extracellular Aβ42 and Aβ40. Together, our genetic and functional data indicate that carriers of PLD3 coding variants have a two-fold increased risk for LOAD and that PLD3 influences APP processing.	SIGNOR-261200
P30411	P34947	0	phosphorylation	down-regulates activity	0.489	Ligand-induced phosphorylation is found at Ser339 and Ser346/Ser348 that could be executed by several G protein-coupled receptor kinases. 32P labeling of peptide 3 containing pS346/pS348 was enhanced 1.5–3-fold as compared with mock-transfected cells in the order GRK6 < GRK5 < GRK2 < GRK4α < GRK3. several endogenous GRKs may phosphorylate the B2R and that the various GRKs, even without apparent effect on total GPCR phosphorylation levels, may induce distinct phosphorylation patterns with possible functional consequences for receptor desensitization and sequestration.	SIGNOR-251208
O00571	P11940	2	binding	up-regulates activity	0.57	In the present study, we indentified the SG marker PABP1 [poly(A)-binding protein 1] as another direct interaction partner of DDX3. Interestingly, down-regulation of DDX3 interfered with SG assembly, led to nuclear accumulation of PABP1 and reduced cell viability following stress. Conversely, supplementation with a shRNA (short hairpin RNA)-resistant DDX3 restored SG formation, the translocation of PABP1 into SGs and cell survival.	SIGNOR-269201
O00327	Q9UJ55	2	binding	down-regulates activity	0.369	Magel2 represses the activity of the Clock:Bmal1 heterodimer in a Per2-luciferase assay. Magel2 interacts with Bmal1 and with Per2 as measured by co-immunoprecipitation in co-transfected cells, and exhibits a subcellular distribution consistent with these interactions when visualized by immunofluorescence. As well, Magel2 induces the redistribution of the subcellular localization of Clock towards the cytoplasm, in contrast to the nucleus-directed effect of Bmal1 on Clock subcellular localization.	SIGNOR-253517
Q9NPB6	P17252	2	binding	up-regulates activity	0.2	The Par complex member Par-6, previously thought to inhibit aPKC, is a potent activator of aPKC in our assays. Par-6 and aPKC interact via PB1 domain heterodimerization, and this interaction activates aPKC by displacing the pseudosubstrate, although full activity requires the Par-6 CRIB-PDZ domains.	SIGNOR-227489
Q06413	Q9UI47	1	transcriptional regulation	up-regulates quantity by expression	0.241	GATA-4 and MEF2C are known to bind to the GATA box 2 in the major promoter of CTNNA3 and this element is essential in directly regulating expression of CTNNA3 in cardiac muscle cells. The co-transfection of GATA-4 with MEF2C leads to a synergistic activation of the CTNNA3 promoter	SIGNOR-265491
P45973	Q15329	0	transcriptional regulation	down-regulates quantity by repression	0.2	We identified for E2F5 a repressor function for HP1a expression.	SIGNOR-261591
P50549	P49137	0	phosphorylation	up-regulates	0.612	Neverthless, some transcription factors, such as e47, er81, srf and creb are also phosphorylated by mk2	SIGNOR-166625
P31751	P46527	1	phosphorylation	down-regulates	0.53	Akt-induced t157 phosphorylation causes retention of p27(kip1) in the cytoplasm, precluding p27(kip1)-induced g1 arrest.[__]Thus, cytoplasmic relocalization of p27(kip1), secondary to akt-mediated phosphorylation, is a novel mechanism whereby the growth inhibitory properties of p27(kip1) are functionally inactivated and the proliferation of breast cancer cells is sustained.	SIGNOR-93122
Q15831	O14744	1	phosphorylation	up-regulates activity	0.2	We found that PRMT5 is a bona fade substrate for LKB1. We identified T132, 139 and 144 residues, located in the TIM-Barrel domain of PRMT5, as target sites for LKB1 phosphorylation. The point mutation of PRMT5 T139/144 to A139/144 drastically decreased its methyltransferase activity, due probably to the loss of its interaction with regulatory proteins such as MEP50, pICln and RiOK1.	SIGNOR-277412
Q99075	P03956	0	cleavage	up-regulates activity	0.33	We have recently reported that HB-EGF is a substrate of MT1-MMP and that removal of the N-terminal fragment of HB-EGFby MT1-MMP converts the former into a hyperactive growthfactor that does not require heparin as a co-factor.	SIGNOR-278096
P29275	P63096	2	binding	up-regulates activity	0.292	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-257039
Q9UBF6	P68400	0	phosphorylation	up-regulates	0.457	Ckbbp1 is phosphorylated in vivo and threonine to alanine mutation at residue 10 abrogates the phosphorylation of ckbbp1 observed in vivo, indicating that ckii is a major kinase that is responsible for in vivo phosphorylation of ckbbp1. As compared with the wild-type ckbbp1 or ckbbp1t10e (in which threonine 10 is replaced by glutamate), overexpression of nonphosphorylatable ckbbp1 (ckbbp1t10a) results in accumulation of ikappabalpha and p27kip1.	SIGNOR-101187
Q9H9S0	P27361	0	phosphorylation	down-regulates	0.492	We found that activation of ERK1 signaling inhibited transactivation activity of Nanog.\|We showed the direct phosphorylation of Nanog by ERK1 and clearly showed that Ser52 is the major phosphorylation site and Ser65 is weakly phosphorylated by ERK1.	SIGNOR-278487
Q02556	P19474	0	ubiquitination	down-regulates quantity	0.638	From these results, we concluded that TRIM21 down-regulated IRF8 and enhanced the secretion of IL-12/23p40 in BD monocytes.\|IRF8 is ubiquitinated by TRIM21, which promotes secretion of IL-12/23p40 after TLR/IFN-\u03b3 stimulation xref .	SIGNOR-278791
Q99626	Q16819	1	transcriptional regulation	up-regulates quantity by expression	0.471	TNF-α-induced down-regulation of CDX2 suppresses MEP1A expression in colitis\|	SIGNOR-253965
Q8IZU3	Q14565	2	binding	up-regulates activity	0.385	The eukaryotic RecA homologues RAD51 and DMC1 function in homology recognition and formation of joint-molecule recombination intermediates during yeast meiosis. We also show that mouse RAD51 and DMC1 establish protein-protein interactions with each other and with the chromosome core component COR1(SCP3) in a two-hybrid system and in vitro binding analyses. These results suggest that the formation of a multiprotein recombination complex associated with the meiotic chromosome cores is essential for the development and fulfillment of the meiotic recombination process.	SIGNOR-264206
P37840	P25098	0	phosphorylation	down-regulates activity	0.2	We found that grk-mediated phosphorylation inhibits synuclein's interaction with both phospholipids and pld2. These findings suggest that gpcrs may be able to indirectly stimulate pld2 activity via their ability to regulate grk-promoted phosphorylation of synuclein.	SIGNOR-78333
O75581	O14641	2	binding	up-regulates activity	0.69	Dvl is required for lrp6 phosphorylation, which is essential for subsequent steps of signal transduction.	SIGNOR-66362
Q13131	O15503	1	phosphorylation	up-regulates quantity by stabilization	0.256	Here we report that AMPK interacts with and mediates phosphorylation of Insig. Thr222 phosphorylation following AMPK activation is required for protein stabilization of Insig-1, inhibition of cleavage and processing of SREBP-1, and lipogenic gene expression in response to metformin or A769662. AMPKα1 subunit associates with Insig-1 in a dose-dependent manner.	SIGNOR-277430
P06493	P15927	1	phosphorylation	up-regulates activity	0.508	Cdc2 family kinases phosphorylate a human cell dna replication factor, rpa, and activate dna replication. therefore, the serines on rpa p34 that were necessary for phosphorylation by cdc2 kinase were also necessary for phosphorylation in the cell	SIGNOR-16975
O95295	Q5S007	0	phosphorylation	down-regulates	0.514	Lrrk2 phosphorylates snapin and inhibits interaction of snapin with snap-25. these data suggest that lrrk2 may regulate neurotransmitter release via control of snapin function by inhibitory phosphorylation. hreonine 117 of snapin is one of the sites phosphorylated by lrrk2	SIGNOR-202436
Q9H7P9	Q92569	2	binding	up-regulates activity	0.249	Through deletion and base substitution mutagenesis we have identified Tyr489 of PLEKHG2 as the site phosphorylated by cSrc.The interaction between PLEKHG2 and the full-length of PIK3R3, but not ABL1, occurs in a tyrosine-phosphorylation-dependent manner.	SIGNOR-273809
Q93009	P62987	1	cleavage	up-regulates quantity	0.735	Here we provide data suggesting that two of the four mammalian ubiquitin precursors, UBA52 and UBA80, are processed mostly post-translationally whereas the other two, UBB and UBC, probably undergo a combination of co- and post-translational processing. Using an unbiased biochemical approach we found that UCHL3, USP9X, USP7, USP5 and Otulin/Gumby/FAM105b are by far the most active DUBs acting on these precursors.	SIGNOR-270823
Q15465	O94991	2	binding	down-regulates activity	0.2	SLITRK5 interacts with SHH and PTCH1. Mechanistically, SLITRK5 binds to hedgehog ligands via its extracellular domain and interacts with PTCH1 via its intracellular domain. SLITRK5 is present in the primary cilium, and loss of SLITRK5 enhances SMO ciliary enrichment upon SHH stimulation. Thus, SLITRK5 is a negative regulator of hedgehog signaling in osteoblasts that may be attractive as a therapeutic target to enhance bone formation.	SIGNOR-268437
Q8TDD2	P31749	0	phosphorylation	up-regulates	0.423	Akt, a member of the ser-ine/threonine-specific protein kinase, was found to phosphorylate osx and dlx5	SIGNOR-252514
P60709	Q9NZI8	0	post transcriptional regulation	up-regulates quantity	0.34	We found that ZBP1 is necessary for netrin-1 stimulated local translation of β-actin mRNA in axonal growth cones. ZBP1 binds to β-actin mRNA in the soma and transports it to the growth cone on microtubules.	SIGNOR-268160
Q13224	P60484	0	dephosphorylation	down-regulates activity	0.296	GluN2B Y1472 site is dephosphorylated by PTEN .	SIGNOR-277165
P30305	P53350	0	phosphorylation	up-regulates activity	0.663	These data indicated that PLK1 phosphorylates CDC25B and that pre-phosphorylation of CDC25B by CDK1/CyclinB enhances its substrate properties for PLK1 in vitro	SIGNOR-267560
P84243	Q9C0A6	0	methylation	up-regulates activity	0.2	SETD5 Exhibits Intrinsic Methyltransferase Activity on H3K36. This assay showed that SETD5 has specific histone methyltransferase activity toward K36 but not for other residues such as K4 and K27 (Figure 8B). we revealed that SETD5 is endowed with H3K36 methyltransferase, which is necessary for RNA elongation and processing and, ultimately, correct gene transcription.	SIGNOR-264622
P55085	P08311	0	cleavage	down-regulates activity	0.526	PAR1E and PAR2E (10 microM) were incubated in the presence of the different proteases \| The enzymes were used at the following concentrations: 0.5 unit/mL thrombin, 2.5 nM trypsin, 20 nM plasmin, 20 nM cathepsin G, 20 nM elastase, 20 nM proteinase 3, and 2 units/mL calpain I and II\|Protease-activated receptors (PARs) mediate cell activation after proteolytic cleavage of their extracellular amino terminus.\|Mass spectrometry studies of PAR2E predicted activation of PAR2 by trypsin through cleavage at the Arg36-Ser37 site, no effect of thrombin, and inactivation of the receptor by plasmin, calpain and leukocyte elastase, cathepsin G, and proteinase 3	SIGNOR-263585
Q99986	P05412	1	phosphorylation	up-regulates	0.512	Vrk1 phosphorylates c-jun in ser63 and ser73 in vitro...VRK1 Activates c-jun dependent transcription	SIGNOR-127073
P29466	Q96EP0	2	cleavage	down-regulates activity	0.2	We show that LUBAC interacted with caspase-1 via HOIP and modified its CARD domain with linear polyubiquitin and that depletion of HOIP or Sharpin resulted in heightened caspase-1 activation and cell death in response to inflammasome activation, unlike what is observed in macrophages. Reciprocally, caspase-1, as well as caspase-8, regulated LUBAC activity by proteolytically processing HOIP at Asp-348 and Asp-387 during the execution of cell death.	SIGNOR-272193
P05771	Q14847	1	phosphorylation	down-regulates activity	0.2	Actin binding of human lim and sh3 protein is regulated by cgmp- and camp-dependent protein kinase phosphorylation on serine 146. Phosphorylation of lasp at ser-146 leads to a redistribution of the actin-bound protein from the tips of the cell membrane to the cytosol, accompanied with a reduced cell migration	SIGNOR-97942
Q9Y5H9	Q9UN71	2	binding	up-regulates activity	0.2	The clustered protocadherins comprise the largest subfamily of the cadherin superfamily and are predominantly expressed in the nervous system. Pcdh-alpha proteins interact with beta1-integrin to promote cell adhesion. They also form oligomers with Pcdh-gamma proteins at the same membrane sites.	SIGNOR-265679
Q99717	P23771	1	transcriptional regulation	up-regulates quantity	0.31	Chromatin immunoprecipitation (ChIP) revealed a subset of the BIG (BMP4 induced genes) signature, including Satb2, Smad6, Hand1, Gadd45γ and Gata3, that was bound by Smad1/5 in the developing mandible, revealing direct Smad-mediated regulation	SIGNOR-268943
P18146	Q15637	2	binding	up-regulates activity	0.295	GNRH1 induces expression of early growth response 1 (EGR1), which interacts with steroidogenic factor 1 (SF1) and paired-like homeodomain transcription factor 1 (PITX1) to regulate Lhb promoter activity.	SIGNOR-254914
Q9BYF1	Q9ULZ1	1	cleavage	up-regulates activity	0.422	ACE2 hydrolyzes the hormone apelin-13 with high catalytic efficiency and cleaves apelin-36, whose C-terminal 13 amino acids are identical to those of apelin-13.	SIGNOR-256316
Q9HCP0	P07948	1	phosphorylation	up-regulates quantity by stabilization	0.2	Although there have been more than 40 reports of mass spectrometric studies on phosphorylation at Lyn-S13, the kinase responsible remained unclear. We succeeded in identifying casein kinase 1γ (CK1γ) as the kinase responsible for phosphorylation of Lyn-S13. In HEK293 cells co-expressing Lyn and CK1γ, the phosphorylation level of Lyn-S13 increased significantly. we concluded that S-palmitoylated CK1γ encounters N-myristoylated Lyn and specifically phosphorylates the Ser-13 residue at the Golgi during intracellular protein traffic, as shown schematically in Fig. 8. Phosphorylated dual-lipid-modified Lyn and S-palmitoylated CK1γ are then transported from the Golgi to the plasma membrane.	SIGNOR-275396
Q66GS9	Q6UVJ0	2	binding	up-regulates activity	0.596	In this study, we demonstrate that the human microcephaly protein, CEP135, directly interacts with hSAS-6 via its carboxyl-terminus and with MTs via its amino-terminus. Unexpectedly, CEP135 also interacts with another microcephaly protein CPAP via its amino terminal domain. Depletion of CEP135 not only perturbed the centriolar localization of CPAP, but also blocked CPAP-induced centriole elongation. We propose that CEP135 may serve as a linker protein that directly connects the central hub protein, hSAS-6, to the outer MTs, and suggest that this interaction stabilizes the proper cartwheel structure for further CPAP-mediated centriole elongation.	SIGNOR-269676
P16298	P0DP24	2	binding	up-regulates	0.511	Calcium-bound calmodulin associates with calcineurin (cn), releasing the phosphatase from the repressive effects on an autoinhibitory domain.	SIGNOR-266322
P49918	P31749	0	phosphorylation	down-regulates	0.447	Cdk inhibitor p57 (kip2) is downregulated by akt during her2-mediated tumorigenicityakt phosphorylates p57 on ser 282 or thr310. Akt activity results in destabilization of p57 by accelerating turnover rate of p57 and enhancing p57 ubiquitination	SIGNOR-252535
P05771	P68104	1	phosphorylation	up-regulates activity	0.2	PKCβI phosphorylates eEF1A at Ser53.our proteomics exploration of cPKC signaling in the nuclei of C2C12 cells demonstrated that the up-regulation of eEF1A intranuclear content, evoked by insulin, is associated with an increase in the phosphorylation of the Ser53 residue of the protein.	SIGNOR-263167
P50148	P34981	2	binding	up-regulates activity	0.491	TRH receptors are textbook calcium-mobilizing receptors: they are coupled to Gq and G11, which activate phospholipase Cβ (PLCβ).	SIGNOR-267202
Q13315	Q02880	1	phosphorylation	down-regulates quantity by destabilization	0.411	Specifically, DNA damage signal, triggered by teniposide (VM-26) treatment, activates ATM, cooperating with CK1 to phosphorylate TOP2β on Ser1134 and Ser1130, respectively, in a canonical degron motif to facilitate β-TrCP binding and subsequent degradation.ATM binds with and phosphorylates TOP2β at Ser1134 to promote its degradation by VM-26.	SIGNOR-277510
Q15306	O75116	0	phosphorylation	up-regulates	0.417	Carock2 phosphorylated irf4 at either of 2 distinct phosphorylation sites, s446 and s447 / rock2-mediated phosphorylation of irf4 regulated the synthesis of il-17 and il-21 and the differentiation of th17 cells.	SIGNOR-167471
O15084	P36873	2	binding	up-regulates activity	0.443	Phosphatase Interactor Targeting K protein (PITK) was previously identified as a novel PP1 targeting subunit implicated in modulating the phosphorylation of the transcriptional regulator heterogeneous nuclear ribonucleoprotein K (hnRNP K)	SIGNOR-264794
P23470	Q8WV28	1	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-254692
P06493	P50548	1	phosphorylation	down-regulates	0.2	Consistent with the in vivo phosphorylation and inactivation by ras, erf is efficiently phosphorylated in vitro by erk2 and cdc2/cyclin b kinases, at sites similar to those detected in vivo. Furthermore, a single mutation at position 526 results in the loss of a specific phosphopeptide both in in vivo and in vitro (by erk2) labeling. Substitution of thr526 for glutamic acid also decreases the repression ability of erf	SIGNOR-29501
O43567	O95295	1	polyubiquitination	up-regulates activity	0.521	RNF13 directly interacted with snapin, a SNAP-25-interacting protein. Interestingly, snapin was ubiquitinated by RNF13 via the lysine-29 conjugated polyubiquitin chain, which in turn promoted the association of snapin with SNAP-25. Consistently, we found an attenuated interaction between snapin and SNAP-25 in the RNF13-null mice. Therefore, these results suggest that RNF13 is involved in the regulation of the SNARE complex, which thereby controls synaptic function.	SIGNOR-272044
P63096	Q99500	2	binding	up-regulates	0.493	Edg-3 and edg-5 couple not only to gibut also to gqand g13	SIGNOR-70713
P04637	P54278	1	transcriptional regulation	up-regulates quantity	0.582	.... numerous potentially novel targets, including the DNA mismatch repair genes MLH1 and PMS2. Both of these genes were determined to be responsive to DNA damage and p53 activation in normal human fibroblasts, and have p53-response elements within their first intron.	SIGNOR-257604
P58417	Q9Y4C0	2	binding	up-regulates	0.375	We show that neurexophilins 1 and 3 but not 4 (neurexophilin 2 is not expressed in rodents) bind to a single individual lns domain, the second overall lns domain in all three alpha-neurexins.	SIGNOR-60643
Q92911	Q06710	0	transcriptional regulation	up-regulates quantity by expression	0.408	Pax8 has an essential role in thyroid organogenesis and differentiation, being the main mediator of thyroid gene transcription, including the NIS gene.	SIGNOR-251990
O60825	P31749	0	phosphorylation	up-regulates activity	0.654	These findings suggest that PKB-dependent binding of 14-3-3s to phospho-Ser483 of cardiac PFK-2 mediates the stimulation of glycolysis by growth factor.	SIGNOR-252555
P29322	P52797	2	binding	up-regulates	0.75	Receptors of the epha group preferentially interact with glycosylphosphatidylinositol (gpi)-linked ligands (of the ephrin-a subclass, which comprises five ligands), while receptors of the ephb group preferentially interact with transmembrane ligands (of the ephrin-b subclass, which comprises three ligands) (table 1). In either case, binding of a ligand results in eph receptor autophosphorylation on tyrosine residues and activation of the kinase activity of the eph receptor	SIGNOR-52387
Q92934	Q15349	0	phosphorylation	down-regulates	0.373	The rsks catalyze the phosphorylation of the pro-apoptotic protein bad at serine 112 to promote cell survival.	SIGNOR-184591
P21675	P04637	1	phosphorylation	down-regulates	0.681	Phosphorylation on thr-55 by taf1 mediates degradation of p53	SIGNOR-123651
Q96BY2	O95071	0	ubiquitination	down-regulates quantity by destabilization	0.345	We demonstrate that UBR5 interacts physically with MOAP-1, ubiquitylates MOAP-1 in vitro and inhibits MOAP-1 stability in cultured cells.	SIGNOR-278581
Q05655	P28329	1	phosphorylation	up-regulates quantity	0.311	Finally, basal ChAT phosphorylation in neurons is mediated predominantly by PKC at Ser-476, with PKC activation increasing phosphorylation at Ser-440 and enhancing ChAT activity.	SIGNOR-249272
Q8IWB6	P53350	0	phosphorylation	down-regulates quantity by destabilization	0.354	We show that phosphorylation of Tex14 by Plk1 during metaphase is required for proteosome dependent degradation of Tex14 and transition from metaphase to anaphase. Phosphorylation of Tex14 Ser431 by Plk1 promotes Tex14 depletion.	SIGNOR-273529
Q13489	P55211	2	binding	down-regulates	0.76	Xiap, birc2 and birc3 were shown to bind pro-casp9. Iaps may suppress casp9 by direct auto-activation of pro-caspase-11	SIGNOR-56481
Q9UJ55	P14373	2	binding	up-regulates activity	0.52	MAGE proteins are a family of proteins that contain a conserved domain known as the MAGE homology domain. Recently, we showed that MAGE proteins function biochemically to bind to and enhance the activity of E3 RING ubiquitin ligases. The E3 RING ubiquitin ligase TRIM27 was identified as a major binding partner of MAGE-L2.	SIGNOR-253513
P06241	P54829	0	dephosphorylation	down-regulates	0.527	Wild-type step(61) dephosphorylates fyn at tyr(420) but not at tyr(531). These results suggest that step regulates the activity of fyn by specifically dephosphorylating the regulatory tyr(420) and may be one mechanism by which fyn activity is decreased within psds.	SIGNOR-86791
Q9NS91	Q9BXW9	1	ubiquitination	up-regulates activity	0.521	In summary, these findings suggest a model, where Rad18 promotes monoubiquitination of FANCD2, and associates with a functional complex involving Rad51, BRCA2, and FANCD2 in the repair of CPT induced stalled or collapsed forks.\|In this study we focused on the role of Rad18 mediated activation of FANCD2 and its functional relationship with BRCA2 and Rad51 proteins in repair of CPT induced lesions.	SIGNOR-278712
Q9HAW4	P53350	0	phosphorylation	down-regulates	0.773	We show that claspin, an adaptor protein required for chk1 activation, becomes degraded at the onset of mitosis. Claspin degradation was triggered by its interaction with, and ubiquitylation by, the scfbtrcp ubiquitin ligase. This interaction was phosphorylation dependent and required the activity of the plk1 kinase	SIGNOR-148442
Q92934	P42574	0	cleavage	up-regulates activity	0.536	Casp3 cleaves bad at asp-61. In addition, caspases convert bad(l) into a pro-death fragment that resembles the short splice variant.	SIGNOR-126727
Q16665	Q9UGL1	1	transcriptional regulation	up-regulates quantity by expression	0.271	To this end, we confirm that KDM3A, KDM4B, KDM4C, KDM5B, KDM5C, and KDM62 are direct targets of HIF-1a while extent the list of known targets to KDM2A, KDM2B, KDM4D, KDM5A, and KDM6A. The results demonstrated that majority of the KDMs were similarly induced (KDM2A, KDM2B, KDM3A, KDM4B, KDM4C, KDM4D, KDM5A, KDM5B, KDM5C, KDM6B, and KDM7A) or repressed (KDM NO66 and KDM1A) by both HIF-1a and HIF-2a.	SIGNOR-271563
P42262	P51608	0	transcriptional regulation	down-regulates quantity by repression	0.323	Bicuculline treatment also leads to an increase in the levels of the transcriptional repressor MeCP2, which binds to the GluR2 promoter along with the corepressors HDAC1 and mSin3A.	SIGNOR-264684
Q9NY61	P49137	0	phosphorylation	up-regulates	0.327	Upon genotoxic stress, aatf is phosphorylated by the checkpoint kinase mk2. Phosphorylation results in the release of aatf from cytoplasmic mrlc3 and subsequent nuclear translocation where aatf binds to the puma, bax and bak promoter regions to repress p53-driven expression of these pro-apoptotic genes.	SIGNOR-191935
Q02763	Q02763	2	phosphorylation	down-regulates activity	0.2	The Tie2 nucleotide binding loop is in an inhibitory conformation, which is not seen in other kinase structures, while its activation loop adopts an activated-like conformation in the absence of phosphorylation. Tyr-897, located in the N-terminal domain, may negatively regulate the activity of Tie2 by preventing dimerization of the kinase domains or by recruiting phosphatases when it is phosphorylated.	SIGNOR-246662
Q13761	P46531	2	binding	down-regulates	0.689	To investigate the possible mechanism of the down-regulation of hes-1 by runx3, we performed western blot and reporter assay and found that runx3 suppressed intracellular domain of notch1 (icn1)-mediated transactivation of notch signaling while it did not alter the expression of icn1 and recombination signal binding protein-j kappa (rbp-j) in smmc7721 cells.	SIGNOR-188338
P46940	P60953	2	binding	down-regulates activity	0.811	Although the name implies that it functions as a GTPase-activating protein, IQGAP1 actually stabilizes Cdc42 and Rac1 in the active, GTP-bound form (5, 8, 17). Thus, IQGAP1 acts as an “anti-GTPase-activating protein” for Cdc42 and Rac1, with marked effects on the cytoskeleton.	SIGNOR-261888
Q9NZA1	P06241	0	phosphorylation	up-regulates activity	0.296	In this paper, we demonstrate that p64 becomes tyrosine phosphorylated when co-expressed with p59(fyn) in HeLa cells.	SIGNOR-274006
P28482	Q92574	1	phosphorylation	down-regulates	0.49	Here, we show that erk may play a critical role in tsc progression through posttranslational inactivation of tsc2. Erk-dependent phosphorylation leads to tsc1-tsc2 dissociation and markedly impairs tsc2 ability to inhibit mtor signalin.	SIGNOR-157162
P31431	O14641	2	binding	up-regulates	0.257	Like other wnt co receptors, syndecan 4 directly interacts with dvl during pcp.	SIGNOR-199635
Q99523	P67870	0	phosphorylation	up-regulates quantity by stabilization	0.2	Phosphorylation of Ser-825 is required for insulin to induce Sort1 in AML12 cells. LC-MS/MS analysis further revealed that serine phosphorylation of Sort1 protein was required for insulin induction of Sort1 in a casein kinase 2-dependent manner and that inhibition of PI3K signaling or prevention of Sort1 phosphorylation accelerated proteasome-dependent Sort1 degradation.	SIGNOR-273636
Q8IZQ1	Q9BXW4	2	binding	up-regulates activity	0.594	Here, we show that ALFY binds selectively to LC3C and the GABARAPs through a LIR in its WD40 domain. Binding of ALFY to GABARAP is indispensable for its recruitment to LC3B-positive structures and, thus, for the clearance of certain p62 structures by autophagy.	SIGNOR-266795
P35232	P04637	2	binding	up-regulates activity	0.443	Our previous studies have shown that prohibitin physically interacts with the marked-box domain of E2F family members and represses their transcriptional activity; in contrast, prohibitin could bind to and enhance the transcriptional activity of p53.	SIGNOR-268978
P50148	P30556	2	binding	up-regulates activity	0.643	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-257017

Q9Y3A6

P49755

2

binding

up-regulates activity

0.568

P28 forms hetero-oligomeric complexes with p23. p23 is a major determinant for efficient targeting of p28 to the ERGIC

SIGNOR-261298

P17936

P68400

0

phosphorylation

up-regulates quantity by stabilization

0.338

The importance of Ser111 and Ser113 as targets for CK2 has also been shown in our laboratory, as mutation of either residue to alanine caused a major decrease in IGFBP-3 phosphorylation by this enzyme in vitro | These results indicate that IGFBP-3 interaction with acid-labile subunit and with the cell surface, both of which involve basic carboxyl-terminal residues, may be modulated by phosphorylation. Relative resistance to proteolysis and poor binding to cells suggest that CK2-phospho-IGFBP-3 may be a significant inhibitor of IGF activity in the extracellular environment.

SIGNOR-250903

P16104

P78527

0

phosphorylation

up-regulates

0.2

Dna-dependentprotein_ kinase_ (dna-pk) that phosphorylate h2ax at dsbs

SIGNOR-192443

P08151

P17612

0

phosphorylation

down-regulates

0.551

We report that activation of PKA retains Gli1 in the cytoplasm. Conversely, inhibition of PKA activity promotes nuclear accumulation of Gli1.We provide direct evidence to support that the cAMP/PKA signaling axis regulates Gli1 protein localization primarily through a site at Thr374. .These data suggest that Thr374 is an important PKA site responsible for PKA phosphorylation and for the transcriptional activity of Gli1.

SIGNOR-253539

O60825

P54646

0

phosphorylation

up-regulates activity

0.443

AMPK phosphorylates and activates heart PFK-2 in vitro and in intact cells. activation of PFK-2 was due to the phosphorylation of Ser466

SIGNOR-250323

P98172

P54762

2

binding

up-regulates

0.827

We show here that despite its lack of kinase activity, ephb6 undergoes inducible tyrosine phosphorylation upon stimulation with the eph-b receptor subfamily ligand ephrin-b1. Overexpression of a catalytically active member of the eph-b subfamily, ephb1, resulted in increased ephb6 phosphorylation. Ephb1-induced ephb6 phosphorylation was ligand-dependent and required the functional catalytic activity of ephb1.

SIGNOR-111851

Q15139

P35670

1

phosphorylation

up-regulates activity

0.296

ATP7B trafficking was markedly reduced by the Ser-478/481/1121/1453 to Ala mutation. We conclude that PKD plays a key role in copper-dependent serine phosphorylation, permitting high levels of ATP7B protein expression and trafficking.

SIGNOR-272295

P46527

Q14012

0

phosphorylation

up-regulates activity

0.305

We also demonstrate that i) CaMKI phosphorylates p27 at Thr157and Thr198 in human cells and at Thr170and Thr197in mouse cells to modulate its subcellular localization;|Collectively, these results suggest that CaMKI is involved in mediating G1 progression by promoting cyclin D1/cdk4 complex formation through site-specific p27 phosphorylation in human lung epithelia.

SIGNOR-261194

P00519

P29474

1

phosphorylation

up-regulates activity

0.2

Two kinases, i.e. abelson-tyrosine protein kinase (ABL)1 and Src were identified as eNOS Tyr81 kinases as their inhibition and down-regulation significantly reduced the basal and Yoda1-induced tyrosine phosphorylation and activity of eNOS.

SIGNOR-277519

P01178-PRO_0000020495

Q92824

0

cleavage

up-regulates quantity

0.2

Oxytocin-extended form is further cleaved by enzymatic activity to yield the nine-amino-acid active peptide, OT. The proteolysis may involve several pro-hormone convertases, convertase 2 (PC2) (20p11-1-11.2) and convertase 5 (PC5) (9q21.3) (Gabreels et al 1998). Both enzymes are found in OT neurosecretory vesicles and are a part of a family of subtilisen/kexinlike convertases (Seidah et al 1994). It is a product of the OT gene located at human gene locus 20p13 (Rao et al 1992). The processing cascade results in the production of neurophysin I and OT extended form (OT-X), which is OT with a C-terminal, three-amino-acid extension.

SIGNOR-270334

Q9P035

P49327

1

chemical activation

up-regulates activity

0.2

Very long-chain fatty acids are produced through a four-step cycle. However, the 3-hydroxyacyl-CoA dehydratase catalyzing the third step in mammals has remained unidentified. Mammals have four candidates, HACD1-4, based on sequence similarities to the recently identified yeast Phs1, although HACD3 and HACD4 share relatively weak similarity. We demonstrate that all four of these human proteins are indeed 3-hydroxyacyl-CoA dehydratases,

SIGNOR-267762

Q00535

P14416

1

phosphorylation

down-regulates activity

0.383

These results indicate that Cdk5-mediated phosphorylation of S321 inhibits DRD2 function, providing a novel regulatory mechanism for dopamine signaling.

SIGNOR-259401

P41970

O15550

0

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-260037

Q02750

Q9Y2G1

1

phosphorylation

down-regulates activity

0.258

Mek1 phosphorylation of Ndt80 therefore provides an elegant way for cells to know when it is safe to enter the first meiotic division.|These observations suggest that phosphorylation of the DBD by Mek1 prevents Ndt80 from binding to MSEs and explains how Mek1 phosphorylation can inhibit Ndt80 activity.

SIGNOR-279416

Q13535

Q14566

1

phosphorylation

up-regulates

0.562

Together these data strongly support the conclusion that mec1 directly targets the s/tq sites in mcm4 and mcm6, although it is formally possible that mec1 and mrc1 activate a different s/tq-directed kinase to target mcm4 and mcm6.

SIGNOR-169450

P34947

P50502

1

phosphorylation

up-regulates activity

0.268

An in vitro screen for novel GRK substrates revealed Hsp70 interacting protein (Hip) as a substrate. GRK5, but not GRK2, bound to and stoichiometrically phosphorylated Hip in vitro. The primary binding domain of GRK5 was mapped to residues 303-319 on Hip, while the major site of phosphorylation was identified to be Ser-346. GRK5 also bound to and phosphorylated Hip on Ser-346 in cells.we found that the phosphorylation of Ser-346 was required for proper agonist-induced internalization of the chemokine receptor CXCR4.

SIGNOR-262877

Q13422

P62136

0

dephosphorylation

up-regulates

0.279

Ikarosis dephosphorylated by protein phosphatase 1 (pp1) via interaction at a consensus pp1-binding motif/ hyperphosphorylation of ikaros promotes its degradation by the ubiquitin/proteasome pathway

SIGNOR-174859

P28324

P24941

0

phosphorylation

up-regulates activity

0.363

Phosphorylation of ELK4 at Thr194 and Ser387 by CDK2 is required for EGF-induced cell transformation.

SIGNOR-278210

Q13285

P10275

2

binding

up-regulates

0.409

Ar suppresses transcription of the lhbeta subunit by interacting with steroidogenic factor-1.

SIGNOR-109996

P78317

P25208

2

binding

up-regulates activity

0.2

Coactivator RNF4 is involved in the GCH gene expression. Through serial deletion and mutagenesis studies of the GCH promoter, we defined the RNF4-responsive element on GCH proximal promoter as a CCAAT box. RNF4 did not possess specific DNA binding activity toward this CCAAT box, which suggests that RNF4 may be a coactivator of the CCAAT boxbinding protein nuclear factor Y (NF-Y). RNF4 is a coactivator for nuclear factor Y on GTP cyclohydrolase I proximal promoter.

SIGNOR-252230

Q8IV08

P05067

2

binding

up-regulates quantity

0.373

Furthermore, PLD3 can be co-immunoprecipitated with APP in cultured cells (Extended Data Figure 4). Together, these studies demonstrate that PLD3 plays a role in APP processing. Over-expression of PLD3 leads to a significant decrease in intracellular APP and extracellular Aβ42 and Aβ40, while knock-down of PLD3 leads to a significant increase in extracellular Aβ42 and Aβ40. Together, our genetic and functional data indicate that carriers of PLD3 coding variants have a two-fold increased risk for LOAD and that PLD3 influences APP processing.

SIGNOR-261200

P30411

P34947

0

phosphorylation

down-regulates activity

0.489

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

SIGNOR-251208

O00571

P11940

2

binding

up-regulates activity

0.57

In the present study, we indentified the SG marker PABP1 [poly(A)-binding protein 1] as another direct interaction partner of DDX3. Interestingly, down-regulation of DDX3 interfered with SG assembly, led to nuclear accumulation of PABP1 and reduced cell viability following stress. Conversely, supplementation with a shRNA (short hairpin RNA)-resistant DDX3 restored SG formation, the translocation of PABP1 into SGs and cell survival.

SIGNOR-269201

O00327

Q9UJ55

2

binding

down-regulates activity

0.369

Magel2 represses the activity of the Clock:Bmal1 heterodimer in a Per2-luciferase assay. Magel2 interacts with Bmal1 and with Per2 as measured by co-immunoprecipitation in co-transfected cells, and exhibits a subcellular distribution consistent with these interactions when visualized by immunofluorescence. As well, Magel2 induces the redistribution of the subcellular localization of Clock towards the cytoplasm, in contrast to the nucleus-directed effect of Bmal1 on Clock subcellular localization.

SIGNOR-253517

Q9NPB6

P17252

2

binding

up-regulates activity

0.2

The Par complex member Par-6, previously thought to inhibit aPKC, is a potent activator of aPKC in our assays. Par-6 and aPKC interact via PB1 domain heterodimerization, and this interaction activates aPKC by displacing the pseudosubstrate, although full activity requires the Par-6 CRIB-PDZ domains.

SIGNOR-227489

Q06413

Q9UI47

1

transcriptional regulation

up-regulates quantity by expression

0.241

GATA-4 and MEF2C are known to bind to the GATA box 2 in the major promoter of CTNNA3 and this element is essential in directly regulating expression of CTNNA3 in cardiac muscle cells. The co-transfection of GATA-4 with MEF2C leads to a synergistic activation of the CTNNA3 promoter

SIGNOR-265491

P45973

Q15329

0

transcriptional regulation

down-regulates quantity by repression

0.2

We identified for E2F5 a repressor function for HP1a expression.

SIGNOR-261591

P50549

P49137

0

phosphorylation

up-regulates

0.612

Neverthless, some transcription factors, such as e47, er81, srf and creb are also phosphorylated by mk2

SIGNOR-166625

P31751

P46527

1

phosphorylation

down-regulates

0.53

Akt-induced t157 phosphorylation causes retention of p27(kip1) in the cytoplasm, precluding p27(kip1)-induced g1 arrest.[__]Thus, cytoplasmic relocalization of p27(kip1), secondary to akt-mediated phosphorylation, is a novel mechanism whereby the growth inhibitory properties of p27(kip1) are functionally inactivated and the proliferation of breast cancer cells is sustained.

SIGNOR-93122

Q15831

O14744

1

phosphorylation

up-regulates activity

0.2

We found that PRMT5 is a bona fade substrate for LKB1. We identified T132, 139 and 144 residues, located in the TIM-Barrel domain of PRMT5, as target sites for LKB1 phosphorylation. The point mutation of PRMT5 T139/144 to A139/144 drastically decreased its methyltransferase activity, due probably to the loss of its interaction with regulatory proteins such as MEP50, pICln and RiOK1.

SIGNOR-277412

Q99075

P03956

0

cleavage

up-regulates activity

0.33

We have recently reported that HB-EGF is a substrate of MT1-MMP and that removal of the N-terminal fragment of HB-EGFby MT1-MMP converts the former into a hyperactive growthfactor that does not require heparin as a co-factor.

SIGNOR-278096

P29275

P63096

2

binding

up-regulates activity

0.292

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-257039

Q9UBF6

P68400

0

phosphorylation

up-regulates

0.457

Ckbbp1 is phosphorylated in vivo and threonine to alanine mutation at residue 10 abrogates the phosphorylation of ckbbp1 observed in vivo, indicating that ckii is a major kinase that is responsible for in vivo phosphorylation of ckbbp1. As compared with the wild-type ckbbp1 or ckbbp1t10e (in which threonine 10 is replaced by glutamate), overexpression of nonphosphorylatable ckbbp1 (ckbbp1t10a) results in accumulation of ikappabalpha and p27kip1.

SIGNOR-101187

Q9H9S0

P27361

0

phosphorylation

down-regulates

0.492

We found that activation of ERK1 signaling inhibited transactivation activity of Nanog.|We showed the direct phosphorylation of Nanog by ERK1 and clearly showed that Ser52 is the major phosphorylation site and Ser65 is weakly phosphorylated by ERK1.

SIGNOR-278487

Q02556

P19474

0

ubiquitination

down-regulates quantity

0.638

From these results, we concluded that TRIM21 down-regulated IRF8 and enhanced the secretion of IL-12/23p40 in BD monocytes.|IRF8 is ubiquitinated by TRIM21, which promotes secretion of IL-12/23p40 after TLR/IFN-\u03b3 stimulation xref .

SIGNOR-278791

Q99626

Q16819

1

transcriptional regulation

up-regulates quantity by expression

0.471

TNF-α-induced down-regulation of CDX2 suppresses MEP1A expression in colitis|

SIGNOR-253965

Q8IZU3

Q14565

2

binding

up-regulates activity

0.385

The eukaryotic RecA homologues RAD51 and DMC1 function in homology recognition and formation of joint-molecule recombination intermediates during yeast meiosis. We also show that mouse RAD51 and DMC1 establish protein-protein interactions with each other and with the chromosome core component COR1(SCP3) in a two-hybrid system and in vitro binding analyses. These results suggest that the formation of a multiprotein recombination complex associated with the meiotic chromosome cores is essential for the development and fulfillment of the meiotic recombination process.

SIGNOR-264206

P37840

P25098

0

phosphorylation

down-regulates activity

0.2

We found that grk-mediated phosphorylation inhibits synuclein's interaction with both phospholipids and pld2. These findings suggest that gpcrs may be able to indirectly stimulate pld2 activity via their ability to regulate grk-promoted phosphorylation of synuclein.

SIGNOR-78333

O75581

O14641

2

binding

up-regulates activity

0.69

Dvl is required for lrp6 phosphorylation, which is essential for subsequent steps of signal transduction.

SIGNOR-66362

Q13131

O15503

1

phosphorylation

up-regulates quantity by stabilization

0.256

Here we report that AMPK interacts with and mediates phosphorylation of Insig. Thr222 phosphorylation following AMPK activation is required for protein stabilization of Insig-1, inhibition of cleavage and processing of SREBP-1, and lipogenic gene expression in response to metformin or A769662. AMPKα1 subunit associates with Insig-1 in a dose-dependent manner.

SIGNOR-277430

P06493

P15927

1

phosphorylation

up-regulates activity

0.508

Cdc2 family kinases phosphorylate a human cell dna replication factor, rpa, and activate dna replication. therefore, the serines on rpa p34 that were necessary for phosphorylation by cdc2 kinase were also necessary for phosphorylation in the cell

SIGNOR-16975

O95295

Q5S007

0

phosphorylation

down-regulates

0.514

Lrrk2 phosphorylates snapin and inhibits interaction of snapin with snap-25. these data suggest that lrrk2 may regulate neurotransmitter release via control of snapin function by inhibitory phosphorylation. hreonine 117 of snapin is one of the sites phosphorylated by lrrk2

SIGNOR-202436

Q9H7P9

Q92569

2

binding

up-regulates activity

0.249

Through deletion and base substitution mutagenesis we have identified Tyr489 of PLEKHG2 as the site phosphorylated by cSrc.The interaction between PLEKHG2 and the full-length of PIK3R3, but not ABL1, occurs in a tyrosine-phosphorylation-dependent manner.

SIGNOR-273809

Q93009

P62987

1

cleavage

up-regulates quantity

0.735

Here we provide data suggesting that two of the four mammalian ubiquitin precursors, UBA52 and UBA80, are processed mostly post-translationally whereas the other two, UBB and UBC, probably undergo a combination of co- and post-translational processing. Using an unbiased biochemical approach we found that UCHL3, USP9X, USP7, USP5 and Otulin/Gumby/FAM105b are by far the most active DUBs acting on these precursors.

SIGNOR-270823

Q15465

O94991

2

binding

down-regulates activity

0.2

SLITRK5 interacts with SHH and PTCH1. Mechanistically, SLITRK5 binds to hedgehog ligands via its extracellular domain and interacts with PTCH1 via its intracellular domain. SLITRK5 is present in the primary cilium, and loss of SLITRK5 enhances SMO ciliary enrichment upon SHH stimulation. Thus, SLITRK5 is a negative regulator of hedgehog signaling in osteoblasts that may be attractive as a therapeutic target to enhance bone formation.

SIGNOR-268437

Q8TDD2

P31749

0

phosphorylation

up-regulates

0.423

Akt, a member of the ser-ine/threonine-specific protein kinase, was found to phosphorylate osx and dlx5

SIGNOR-252514

P60709

Q9NZI8

0

post transcriptional regulation

up-regulates quantity

0.34

We found that ZBP1 is necessary for netrin-1 stimulated local translation of β-actin mRNA in axonal growth cones. ZBP1 binds to β-actin mRNA in the soma and transports it to the growth cone on microtubules.

SIGNOR-268160

Q13224

P60484

0

dephosphorylation

down-regulates activity

0.296

GluN2B Y1472 site is dephosphorylated by PTEN .

SIGNOR-277165

P30305

P53350

0

phosphorylation

up-regulates activity

0.663

These data indicated that PLK1 phosphorylates CDC25B and that pre-phosphorylation of CDC25B by CDK1/CyclinB enhances its substrate properties for PLK1 in vitro

SIGNOR-267560

P84243

Q9C0A6

0

methylation

up-regulates activity

0.2

SETD5 Exhibits Intrinsic Methyltransferase Activity on H3K36. This assay showed that SETD5 has specific histone methyltransferase activity toward K36 but not for other residues such as K4 and K27 (Figure 8B). we revealed that SETD5 is endowed with H3K36 methyltransferase, which is necessary for RNA elongation and processing and, ultimately, correct gene transcription.

SIGNOR-264622

P55085

P08311

0

cleavage

down-regulates activity

0.526

PAR1E and PAR2E (10 microM) were incubated in the presence of the different proteases | The enzymes were used at the following concentrations: 0.5 unit/mL thrombin, 2.5 nM trypsin, 20 nM plasmin, 20 nM cathepsin G, 20 nM elastase, 20 nM proteinase 3, and 2 units/mL calpain I and II|Protease-activated receptors (PARs) mediate cell activation after proteolytic cleavage of their extracellular amino terminus.|Mass spectrometry studies of PAR2E predicted activation of PAR2 by trypsin through cleavage at the Arg36-Ser37 site, no effect of thrombin, and inactivation of the receptor by plasmin, calpain and leukocyte elastase, cathepsin G, and proteinase 3

SIGNOR-263585

Q99986

P05412

1

phosphorylation

up-regulates

0.512

Vrk1 phosphorylates c-jun in ser63 and ser73 in vitro...VRK1 Activates c-jun dependent transcription

SIGNOR-127073

P29466

Q96EP0

2

cleavage

down-regulates activity

0.2

We show that LUBAC interacted with caspase-1 via HOIP and modified its CARD domain with linear polyubiquitin and that depletion of HOIP or Sharpin resulted in heightened caspase-1 activation and cell death in response to inflammasome activation, unlike what is observed in macrophages. Reciprocally, caspase-1, as well as caspase-8, regulated LUBAC activity by proteolytically processing HOIP at Asp-348 and Asp-387 during the execution of cell death.

SIGNOR-272193

P05771

Q14847

1

phosphorylation

down-regulates activity

0.2

Actin binding of human lim and sh3 protein is regulated by cgmp- and camp-dependent protein kinase phosphorylation on serine 146. Phosphorylation of lasp at ser-146 leads to a redistribution of the actin-bound protein from the tips of the cell membrane to the cytosol, accompanied with a reduced cell migration

SIGNOR-97942

Q9Y5H9

Q9UN71

2

binding

up-regulates activity

0.2

The clustered protocadherins comprise the largest subfamily of the cadherin superfamily and are predominantly expressed in the nervous system. Pcdh-alpha proteins interact with beta1-integrin to promote cell adhesion. They also form oligomers with Pcdh-gamma proteins at the same membrane sites.

SIGNOR-265679

Q99717

P23771

1

transcriptional regulation

up-regulates quantity

0.31

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

SIGNOR-268943

P18146

Q15637

2

binding

up-regulates activity

0.295

GNRH1 induces expression of early growth response 1 (EGR1), which interacts with steroidogenic factor 1 (SF1) and paired-like homeodomain transcription factor 1 (PITX1) to regulate Lhb promoter activity.

SIGNOR-254914

Q9BYF1

Q9ULZ1

1

cleavage

up-regulates activity

0.422

ACE2 hydrolyzes the hormone apelin-13 with high catalytic efficiency and cleaves apelin-36, whose C-terminal 13 amino acids are identical to those of apelin-13.

SIGNOR-256316

Q9HCP0

P07948

1

phosphorylation

up-regulates quantity by stabilization

0.2

Although there have been more than 40 reports of mass spectrometric studies on phosphorylation at Lyn-S13, the kinase responsible remained unclear. We succeeded in identifying casein kinase 1γ (CK1γ) as the kinase responsible for phosphorylation of Lyn-S13. In HEK293 cells co-expressing Lyn and CK1γ, the phosphorylation level of Lyn-S13 increased significantly. we concluded that S-palmitoylated CK1γ encounters N-myristoylated Lyn and specifically phosphorylates the Ser-13 residue at the Golgi during intracellular protein traffic, as shown schematically in Fig. 8. Phosphorylated dual-lipid-modified Lyn and S-palmitoylated CK1γ are then transported from the Golgi to the plasma membrane.

SIGNOR-275396

Q66GS9

Q6UVJ0

2

binding

up-regulates activity

0.596

In this study, we demonstrate that the human microcephaly protein, CEP135, directly interacts with hSAS-6 via its carboxyl-terminus and with MTs via its amino-terminus. Unexpectedly, CEP135 also interacts with another microcephaly protein CPAP via its amino terminal domain. Depletion of CEP135 not only perturbed the centriolar localization of CPAP, but also blocked CPAP-induced centriole elongation. We propose that CEP135 may serve as a linker protein that directly connects the central hub protein, hSAS-6, to the outer MTs, and suggest that this interaction stabilizes the proper cartwheel structure for further CPAP-mediated centriole elongation.

SIGNOR-269676

P16298

P0DP24

2

binding

up-regulates

0.511

Calcium-bound calmodulin associates with calcineurin (cn), releasing the phosphatase from the repressive effects on an autoinhibitory domain.

SIGNOR-266322

P49918

P31749

0

phosphorylation

down-regulates

0.447

Cdk inhibitor p57 (kip2) is downregulated by akt during her2-mediated tumorigenicityakt phosphorylates p57 on ser 282 or thr310. Akt activity results in destabilization of p57 by accelerating turnover rate of p57 and enhancing p57 ubiquitination

SIGNOR-252535

P05771

P68104

1

phosphorylation

up-regulates activity

0.2

PKCβI phosphorylates eEF1A at Ser53.our proteomics exploration of cPKC signaling in the nuclei of C2C12 cells demonstrated that the up-regulation of eEF1A intranuclear content, evoked by insulin, is associated with an increase in the phosphorylation of the Ser53 residue of the protein.

SIGNOR-263167

P50148

P34981

2

binding

up-regulates activity

0.491

TRH receptors are textbook calcium-mobilizing receptors: they are coupled to Gq and G11, which activate phospholipase Cβ (PLCβ).

SIGNOR-267202

Q13315

Q02880

1

phosphorylation

down-regulates quantity by destabilization

0.411

Specifically, DNA damage signal, triggered by teniposide (VM-26) treatment, activates ATM, cooperating with CK1 to phosphorylate TOP2β on Ser1134 and Ser1130, respectively, in a canonical degron motif to facilitate β-TrCP binding and subsequent degradation.ATM binds with and phosphorylates TOP2β at Ser1134 to promote its degradation by VM-26.

SIGNOR-277510

Q15306

O75116

0

phosphorylation

up-regulates

0.417

Carock2 phosphorylated irf4 at either of 2 distinct phosphorylation sites, s446 and s447 / rock2-mediated phosphorylation of irf4 regulated the synthesis of il-17 and il-21 and the differentiation of th17 cells.

SIGNOR-167471

O15084

P36873

2

binding

up-regulates activity

0.443

Phosphatase Interactor Targeting K protein (PITK) was previously identified as a novel PP1 targeting subunit implicated in modulating the phosphorylation of the transcriptional regulator heterogeneous nuclear ribonucleoprotein K (hnRNP K)

SIGNOR-264794

P23470

Q8WV28

1

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-254692

P06493

P50548

1

phosphorylation

down-regulates

0.2

Consistent with the in vivo phosphorylation and inactivation by ras, erf is efficiently phosphorylated in vitro by erk2 and cdc2/cyclin b kinases, at sites similar to those detected in vivo. Furthermore, a single mutation at position 526 results in the loss of a specific phosphopeptide both in in vivo and in vitro (by erk2) labeling. Substitution of thr526 for glutamic acid also decreases the repression ability of erf

SIGNOR-29501

O43567

O95295

1

polyubiquitination

up-regulates activity

0.521

RNF13 directly interacted with snapin, a SNAP-25-interacting protein. Interestingly, snapin was ubiquitinated by RNF13 via the lysine-29 conjugated polyubiquitin chain, which in turn promoted the association of snapin with SNAP-25. Consistently, we found an attenuated interaction between snapin and SNAP-25 in the RNF13-null mice. Therefore, these results suggest that RNF13 is involved in the regulation of the SNARE complex, which thereby controls synaptic function.

SIGNOR-272044

P63096

Q99500

2

binding

up-regulates

0.493

Edg-3 and edg-5 couple not only to gibut also to gqand g13

SIGNOR-70713

P04637

P54278

1

transcriptional regulation

up-regulates quantity

0.582

.... numerous potentially novel targets, including the DNA mismatch repair genes MLH1 and PMS2. Both of these genes were determined to be responsive to DNA damage and p53 activation in normal human fibroblasts, and have p53-response elements within their first intron.

SIGNOR-257604

P58417

Q9Y4C0

2

binding

up-regulates

0.375

We show that neurexophilins 1 and 3 but not 4 (neurexophilin 2 is not expressed in rodents) bind to a single individual lns domain, the second overall lns domain in all three alpha-neurexins.

SIGNOR-60643

Q92911

Q06710

0

transcriptional regulation

up-regulates quantity by expression

0.408

Pax8 has an essential role in thyroid organogenesis and differentiation, being the main mediator of thyroid gene transcription, including the NIS gene.

SIGNOR-251990

O60825

P31749

0

phosphorylation

up-regulates activity

0.654

These findings suggest that PKB-dependent binding of 14-3-3s to phospho-Ser483 of cardiac PFK-2 mediates the stimulation of glycolysis by growth factor.

SIGNOR-252555

P29322

P52797

2

binding

up-regulates

0.75

Receptors of the epha group preferentially interact with glycosylphosphatidylinositol (gpi)-linked ligands (of the ephrin-a subclass, which comprises five ligands), while receptors of the ephb group preferentially interact with transmembrane ligands (of the ephrin-b subclass, which comprises three ligands) (table 1). In either case, binding of a ligand results in eph receptor autophosphorylation on tyrosine residues and activation of the kinase activity of the eph receptor

SIGNOR-52387

Q92934

Q15349

0

phosphorylation

down-regulates

0.373

The rsks catalyze the phosphorylation of the pro-apoptotic protein bad at serine 112 to promote cell survival.

SIGNOR-184591

P21675

P04637

1

phosphorylation

down-regulates

0.681

Phosphorylation on thr-55 by taf1 mediates degradation of p53

SIGNOR-123651

Q96BY2

O95071

0

ubiquitination

down-regulates quantity by destabilization

0.345

We demonstrate that UBR5 interacts physically with MOAP-1, ubiquitylates MOAP-1 in vitro and inhibits MOAP-1 stability in cultured cells.

SIGNOR-278581

Q05655

P28329

1

phosphorylation

up-regulates quantity

0.311

Finally, basal ChAT phosphorylation in neurons is mediated predominantly by PKC at Ser-476, with PKC activation increasing phosphorylation at Ser-440 and enhancing ChAT activity.

SIGNOR-249272

Q8IWB6

P53350

0

phosphorylation

down-regulates quantity by destabilization

0.354

We show that phosphorylation of Tex14 by Plk1 during metaphase is required for proteosome dependent degradation of Tex14 and transition from metaphase to anaphase. Phosphorylation of Tex14 Ser431 by Plk1 promotes Tex14 depletion.

SIGNOR-273529

Q13489

P55211

2

binding

down-regulates

0.76

Xiap, birc2 and birc3 were shown to bind pro-casp9. Iaps may suppress casp9 by direct auto-activation of pro-caspase-11

SIGNOR-56481

Q9UJ55

P14373

2

binding

up-regulates activity

0.52

MAGE proteins are a family of proteins that contain a conserved domain known as the MAGE homology domain. Recently, we showed that MAGE proteins function biochemically to bind to and enhance the activity of E3 RING ubiquitin ligases. The E3 RING ubiquitin ligase TRIM27 was identified as a major binding partner of MAGE-L2.

SIGNOR-253513

P06241

P54829

0

dephosphorylation

down-regulates

0.527

Wild-type step(61) dephosphorylates fyn at tyr(420) but not at tyr(531). These results suggest that step regulates the activity of fyn by specifically dephosphorylating the regulatory tyr(420) and may be one mechanism by which fyn activity is decreased within psds.

SIGNOR-86791

Q9NS91

Q9BXW9

1

ubiquitination

up-regulates activity

0.521

In summary, these findings suggest a model, where Rad18 promotes monoubiquitination of FANCD2, and associates with a functional complex involving Rad51, BRCA2, and FANCD2 in the repair of CPT induced stalled or collapsed forks.|In this study we focused on the role of Rad18 mediated activation of FANCD2 and its functional relationship with BRCA2 and Rad51 proteins in repair of CPT induced lesions.

SIGNOR-278712

Q9HAW4

P53350

0

phosphorylation

down-regulates

0.773

We show that claspin, an adaptor protein required for chk1 activation, becomes degraded at the onset of mitosis. Claspin degradation was triggered by its interaction with, and ubiquitylation by, the scfbtrcp ubiquitin ligase. This interaction was phosphorylation dependent and required the activity of the plk1 kinase

SIGNOR-148442

Q92934

P42574

0

cleavage

up-regulates activity

0.536

Casp3 cleaves bad at asp-61. In addition, caspases convert bad(l) into a pro-death fragment that resembles the short splice variant.

SIGNOR-126727

Q16665

Q9UGL1

1

transcriptional regulation

up-regulates quantity by expression

0.271

To this end, we confirm that KDM3A, KDM4B, KDM4C, KDM5B, KDM5C, and KDM62 are direct targets of HIF-1a while extent the list of known targets to KDM2A, KDM2B, KDM4D, KDM5A, and KDM6A. The results demonstrated that majority of the KDMs were similarly induced (KDM2A, KDM2B, KDM3A, KDM4B, KDM4C, KDM4D, KDM5A, KDM5B, KDM5C, KDM6B, and KDM7A) or repressed (KDM NO66 and KDM1A) by both HIF-1a and HIF-2a.

SIGNOR-271563

P42262

P51608

0

transcriptional regulation

down-regulates quantity by repression

0.323

Bicuculline treatment also leads to an increase in the levels of the transcriptional repressor MeCP2, which binds to the GluR2 promoter along with the corepressors HDAC1 and mSin3A.

SIGNOR-264684

Q9NY61

P49137

0

phosphorylation

up-regulates

0.327

Upon genotoxic stress, aatf is phosphorylated by the checkpoint kinase mk2. Phosphorylation results in the release of aatf from cytoplasmic mrlc3 and subsequent nuclear translocation where aatf binds to the puma, bax and bak promoter regions to repress p53-driven expression of these pro-apoptotic genes.

SIGNOR-191935

Q02763

2

phosphorylation

down-regulates activity

0.2

The Tie2 nucleotide binding loop is in an inhibitory conformation, which is not seen in other kinase structures, while its activation loop adopts an activated-like conformation in the absence of phosphorylation. Tyr-897, located in the N-terminal domain, may negatively regulate the activity of Tie2 by preventing dimerization of the kinase domains or by recruiting phosphatases when it is phosphorylated.

SIGNOR-246662

Q13761

P46531

2

binding

down-regulates

0.689

To investigate the possible mechanism of the down-regulation of hes-1 by runx3, we performed western blot and reporter assay and found that runx3 suppressed intracellular domain of notch1 (icn1)-mediated transactivation of notch signaling while it did not alter the expression of icn1 and recombination signal binding protein-j kappa (rbp-j) in smmc7721 cells.

SIGNOR-188338

P46940

P60953

2

binding

down-regulates activity

0.811

Although the name implies that it functions as a GTPase-activating protein, IQGAP1 actually stabilizes Cdc42 and Rac1 in the active, GTP-bound form (5, 8, 17). Thus, IQGAP1 acts as an “anti-GTPase-activating protein” for Cdc42 and Rac1, with marked effects on the cytoskeleton.

SIGNOR-261888

Q9NZA1

P06241

0

phosphorylation

up-regulates activity

0.296

In this paper, we demonstrate that p64 becomes tyrosine phosphorylated when co-expressed with p59(fyn) in HeLa cells.

SIGNOR-274006

P28482

Q92574

1

phosphorylation

down-regulates

0.49

Here, we show that erk may play a critical role in tsc progression through posttranslational inactivation of tsc2. Erk-dependent phosphorylation leads to tsc1-tsc2 dissociation and markedly impairs tsc2 ability to inhibit mtor signalin.

SIGNOR-157162

P31431

O14641

2

binding

up-regulates

0.257

Like other wnt co receptors, syndecan 4 directly interacts with dvl during pcp.

SIGNOR-199635

Q99523

P67870

0

phosphorylation

up-regulates quantity by stabilization

0.2

Phosphorylation of Ser-825 is required for insulin to induce Sort1 in AML12 cells. LC-MS/MS analysis further revealed that serine phosphorylation of Sort1 protein was required for insulin induction of Sort1 in a casein kinase 2-dependent manner and that inhibition of PI3K signaling or prevention of Sort1 phosphorylation accelerated proteasome-dependent Sort1 degradation.

SIGNOR-273636

Q8IZQ1

Q9BXW4

2

binding

up-regulates activity

0.594

Here, we show that ALFY binds selectively to LC3C and the GABARAPs through a LIR in its WD40 domain. Binding of ALFY to GABARAP is indispensable for its recruitment to LC3B-positive structures and, thus, for the clearance of certain p62 structures by autophagy.

SIGNOR-266795

P35232

P04637

2

binding

up-regulates activity

0.443

Our previous studies have shown that prohibitin physically interacts with the marked-box domain of E2F family members and represses their transcriptional activity; in contrast, prohibitin could bind to and enhance the transcriptional activity of p53.

SIGNOR-268978

P50148

P30556

2

binding

up-regulates activity

0.643

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-257017